the - university of toronto t-space · first reported by mobius in 1888. although the seventh...
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CEPHALOMETRIC COMPARISON OF THE
CRWlOFAClAL SMLETAL MORPHOLOGY BETWEEN
MOBIUS SYNDROME A N D NON-SYNDROMIC CONTROLS
Susette M. lnstrum
A thesis submitted in conformity with the requirements for the
Degree of Master o f Science, Department o f Orthodonties.
Faculty of Dentistry, The University of Toronto
O Copyright by Susette M. Instrum 1999
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National Library (*I of Canada Bibliothèque nationale du Canada
Acquisitions and Acquisitions et Bibliographic Services services bibliographiques
395 Wellington Street 395. rue Wellington OtlawaON K1AON4 Ottawa ON Kt A ON4 Canada Canada
Your lils Votre relenmca
Our I% Norra reierence
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The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts ~ o m it Ni la thèse ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation.
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1 would like to thank my cornmittee rnembers Dr. Ross. Dr. Rossouw. Dr. Tompson. and
Dr. Zuker for their assistance and suidance with this project. 1 would like to offer a special
acknowledgment to Dr. Ross for always challen$ng rny ideas and Dr. Tompson for
supportin; me unconditionally.
Thank you to The Burlington Growth Center. Derek Stephens for his statistical expertise.
Lynn Cornfoot for her assistance with the cephalometric tracing. and Dr Faille t'or
providing the additional sample.
Completing this last year has been very cliallenginy and would not have been possible
without my husband who always believed in my abilities and always reminded me to l ive
life to the fullest. 1 would also like to acknowledge rny daughter Karhryn Rene who added
an extra chailense to the year but has proven to be my yreatest accomplishment.
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TABLE OF CONTENTS PP.
Abstract 1 *.
Acknowledgments 11 *. .
Table of Contents III
List of Tables
List of Figures
List of Appendices
Introduction
Literature Review
Facial Paralysis
Diagnostic Criteria
Pathogenesis
E tio logy
Craniofacial Morphology and Orofacial Manifestations
Other Features
Radiographie Findings
Surgical interventions
Conclusions
Statement of the Problem
Objectives
Hypo theses
Methods and Materials
Resu 1 ts
Discussion
Conclusions
Further Research
References
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iv
LIST OF TABLES Pe,
Table 1 : Differential diagnosis of facial paralysis
Table 7: Surnrnary of features associated with Mobius syndrome
Table 3: Necrospy reports
Table 4 a: Environmental causes of Mobius syndrome
Table 4 b: Genetic cases of Mobius svndrorne
Table 4 c: Proposed location of gene for Mobius syndrome
Table 5: Sumrnary of cranial nerves and associated functions
Table 6: Distribution of cranial nerve palsies in Mobius syndrome (Engler et al 1979)
Tab
Tab
Tab
e 7: Distribution of cranial nerve palsies in Mobius syndrome (Carr et al. 1997)
e 8: Muscle of the face innervated by cranial nenie (VU) and associated actions
e 9: Muscles of mastication innervated by cranial nerve (V) and associated actions
Table 10: Staternents of micrognathia in Mobius syndrnrne and respective references
Table 1 1 : Craniofacial assessments of 186 cases of Mobius syndrome
Table 12: Reports of micrognathia in young individuais with Mobius syndrome
Table 13 : Mobius sample: ase. yender, cranial nerve and time of lateral cephalogram
Table 14: Age and sex distribution of sample and control
Table 15: Results of Univariate Anova for primary Mobius sample and control
Table 16: Means and standard deviations for secondary Mobius sarnple versus control
Table 17: Means for rnavillary length, mandibular length and unit length difference
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\
- LIST OF FIGURES
Figure 1 a: Mobius syndrome - frontal view
Figure 1 b: Mobius syndrome - profile view
Figure 2: Skeletal components of Class I I blalocclusions
Figre 3 : Flap pnor to gracilis muscle transfer
Figure 4: Superficial location of graci l is muscle
Figure 5a: klobius syndrome - smile prior to reanimation surgery
Figure 5b: Mobius syndrome - smile after reanirnation surgery
Figure 6a: blobius syndrome - smile after reanimation surgery - right
Figure 6b: Mobius syndrome - smile after reanimation surgery - right and left
Figure 7: Skeletal landmarks on lateral cephalograri;
Figure 8a: Linear measurements on lateral cephalogram
Figure 8b: Anyular measurements on lateral cephalogram
Figure 8c: Proportional measurements on lateral cep halogram
Figure 9a: hlaxillary length of primary sample and control
Figure 9b: Mandibular iength of prirnary sample and control
Figure IOa: Mean tracing; primary sample superimposed on control on Ba-Na
Figure lob: Mean tracing; primary sample superimposed on control on ANS-PNS
Figure 1Oc: Mean tracing; primary sample superimposed on conrrol on MP
Figure 1 1 : Lateral cephalometric radiograph- primary sample
Figure 12: Lateral cephalometric radioyraph- secondary sample
Figure D a : Mean tracing; secondary sample superimposed on control on Ba-Na
Figure 13b: Mean tracing; secondary sample superimposed on control on ANS-PNS
Figure 13c: Mean tracing; secondary sample superimposed on control on MP
Pe.
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LIST OF APPENDICES PP. -
Appendix A: Operational Definitions 79
Appendix B Raw Data - Primary Sample 52
Xppendix C: Raw Data - Secondary Sample S5
Appendix D: Raw Data - Control for Primary Sample 87
Appendix E: Raw Data - Control for Secondary Sample 92
Appendix F : Cephalometric Tracings - Primary Sarnple 94
Appendis G: Crphalometric Tracings - Sacondaq Sampla 98
Appendix H: Statistical Data 1 O0
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INTRODUCTION
Mobius syndrome is a rare form of conjenital non-progressive facial paralysis which was
first reported by Mobius in 1888. Although the seventh cranial nerve is always involved,
cranial nerves III, IV, V, VI, VIII, IX, X, XI and X I may also be affected. Craniofacial and
orofacial abnormalities are included in the diagnostic criteria for Mobius syndrome and
include: microstornia, cleft palate, bi fid uvula, high arched palate. palatal palsy, high nasal
bridge, midface prominence, l i p incorn petency with an evened and prominent lower 1 ip,
hypoplasia and/or paralysis of the tongue, exremal ear defects and micrognathia. Eye, limb
and muscle abnonalities may also be present. This literature review provides a detailed
overview of the syndrome, dong with the reported etiology and pathogenesis. The
diagnostic criteria and associated features of the syndrome are reviewed and the current lack
of evidence to include micrognathia. alonj with the need for controlled cephalometric
studies, is explained. Finallv, the surgical interventions for individuals with Mobius
syndrome are described and future studies to determine their potential morphological
benefits with respect to growth and development are proposed.
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LITERATURE REVIEW
Facial Paralvsis
The differential diagnosis of facial paralysis is extensive and includes: metabolic, vascular,
imrnunologic. traumatic, infectious, toxic, neoplastic, idiopathic, and congenital (Hora &
Elwell 1966, May & Klein 1994, Cwach et al. 1997) (Table 1 ).
Congeni ta1 Facial Paralvsis
Congenital Facial paralysis occurs in approximately 1.4 70 of live binhs (Carr et al. 1997)
and is associated with obstetric or spontaneoushon-obstetric causes (Bonar & Owens 1929.
Carr et al. 1997). Obstetric cases of facial paralysis may be caused by forceps delivery or
inherent pressure factors such as antepartum and intrapartum compression. Spontaneous or
non-obstetric causes of facial paralysis include: Myotonic dystrophy, Facioscapulohumeral
dystrophy. materna1 ingestion of Thalidomide. and Mohius syndrome (Cwach et al. 1997).
Mdbius Svndrome
Mobius syndrome was originally described by von Graefe in 1880, but Illobius was the first
to report the syndrome in 1888 (Engler et ai. 1979). Mobius collected 43 cases of acquired
and congenital nerve paisies and classified them into seven groups. One group consisted of
six cases of congenital bilateral abducens and facial palsy. Mobius believed that the
condition was due to degeneration and atrophy of the invoived nuclei and was unable to find
a single case of abducens-facial paralysis which developed during childhood (Thomas
1898). The term "Mobius syndrome" has been used by medical historians but other terms
include: congenital facial diplegia, congenital abducens-facial paralysis, congenital
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oculofacial paralysis, congenital nuclear agenesis, congenital paralysis of the sixth and
seventh nerve, infantile Kemschwund. akinesia alegra, and infantile nuclear atrophy
(Cadwalader 1927, Masaki 1971, Engler et al. 1979). Although Evlobius was the first to
report the syndrome in 1888, the syndrome has been referred to as both "Mobius" and
"Moebius" syndrome.
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Table 1: Diffcrcntiiil Diagnosis of Facial Pmlysis (May and Klein 1994. Cwacli et al. 1997)
Ditibstcs nicllitus Acutc interniittcnt porpliyria Wcniicke-Korsrrkoff Syndroiiie H~~pcrthyro idism
rraumatic 3asilar skull frxturc 3ilatcr+,l mandibulx frdctures 3ilatcwl tcmponl bone fractures Utitude parilysis ;cuba diving
ï'osic 3thylenc glycol ingestion 4rsenic intoxication Z d o n monoside
[nfcctious Lynie disease Aquired immune deficienq syndrome Mristoiditis Syphilis Leuospirosis Otitis nicdia Tctmus Diphthcria Sculet fcver Tuberculosis Leprosy Mycoplasmli pncuinonili Malaria Trichinosis Herpes siniples virus Epstein-Barr virus Varicella-zoster virus Cossakic vims
Immunoloric Multiple sclerosis My sisthenia gravis
Polyrirtcritis nodosa Tcinponl artertitis Sysieniic Lupus Eqdiriialosus Sclerodernia Sjogren's syndrome iMelkersson-Roscntfr31 sy ndroiiic Pontine Iieniorrtiage or iscficniia
Ncoplasm Pontine glionias Xeurofibromatosis Meningeal carcinonia ptosis Leukemia Ly mphoma Fibrous dysplrisiri
Con~eni td biobius s~ndronie Myotonic dystroptiy Facioscapulohumenl dystrophy Materna1 injestion of Tlialidomide Birth tmunta
Othcr - Bell's pais' Benign intrxranial Iiypencnsion Sarcodosis Stevens Jolmson syndrome Amyuophic laterd sclcrosis Polomy clitis Murnps Influenza .4rôovirus kleningitis Encephalitis Botulism Guillaine Barre
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Diagnostic Criteria
Mobius syndrome is usually diagnosed soon after birth. The facial palsy is typicall y noticed
by the parents during the first few days of life due to the child's difficulty in nursing and
incomplete closure of the eyelids during sleep. The parents becorne concemed with their
child's inability to smile and the lack of facial expression when crying (Henderson 1939).
The criteria for diagnosis rernains difficult to define. This dificulty is most likely due to the
variable expressivity of the syndrome and the low incidence of reported cases. There are
approximately 200 reported cases to date (MacDermot et al. 1990) with males and females
being equally affected (Gorlin et al. 1990). The diagnostic criteria of Mobius syndrome has
stemmed from a collaboration of the most typically found features described in the cases
reported (Table 2). Controlled studies to determine the diagnostic criteria have not been
conducted and thus little scientific evidence has rmerged.
Accordhg to Mobius (1888). the syndrome consisted of bilateral facial weakness and
bilateral abducens palsies. Richards ( 1953) reviewed the published papers up to 1953 and
described the essential features of Mobius syndrome as :
1. unilateral or bilateral, complete or incomplete facial weakness;
2. unilateral or bilateral loss of abduction of the eye;
3. primas, or secondary congenital abnomalities of the extremities; and
4. possible other involvement of the branchial musculature.
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6
Although Richards (1953) included unilateral facial paralysis in his diagnostic criteria,
Kumar ( 1990), Zuker ( 1990) and May & Klein ( 1 994) felt that bilatera
more typical of Mobius syndrome.
1 facial paralysis was
Roger's ( 1 969) additions to the diagnostic criteria included oculomotor, motor branch of the
trigem inal. glossopharyngeal and h y poglossal cranial nerve palsies. dong with ear
anomalies and mental retardation. Baraitser (1977) insisted that limb malformations be
included in the diagnostic criteria. Kumar (1990) established guidelines for diagnosing
Mobius syndrome based on previously published case reports of Henderson (1 93 9),
Richards (1953) and Baraitser (1977). Along with the "essential" complete or partial facial
paralysis and the often present limb malformations. Kumar ( 1990) also described additional
clinical features which could be present and would be helpful in making a clinical diagnosis
of blobius syndrome. These additional features included bilateral or unilateral ocular nerve
palsies. hypoplasia of the tongue. speech and swallowing problerns. malformations of the
orofacial complex and anomalies of the musculoskeletal system.
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+ . . - . . - =cniq.f$diii - :, -
" '
* mask-like facies
* high nasal bndgc
* rnicrostonii~
* uppcr micifacc prominencc
* micrognüthia
* e ~ t r t c d and proniincni 101s cr lip
* lip inconipetcncy
* bifid u\+ulri
* clcft palatc
* p m l j sis of the tongue
hypoplasiii of tlie tongue
* cstcrnril ear defccts
* absent digits
inability to abdiici the eyc Iritcrally
11' pcrtclorisiii
incoiiipicic clostirc of e> clids
sniall palpcbrdl fissures
cpicmthic folds
I O*.. :. .-. .-. . . : . . . . .>:< .?: . . .. . , , - F+on& ,...,+y... . , . -. . . Pro ... b h s : . ~ . . ~ : ~ s ~ ~ s - T. .z ....-.\,a ;:;--.-.œ &->.-..a?:~:--, . ... S . * :.. .. .,., .. . . - .. .. ~ . I . i * . - - . ~ . . . - d . - ' . r.4-
* nicntal rctardation
* ribscncc of stcmai hcad of
pecioralis riitiscle
* brmcliial niusclc dcf'ccts
* rib defccts
* Klippcl-Fcil rinotrialy
* Polarid- Mobiiis s> ndrornc
ps~~chosocial concems
speech problctns
fccding roblcins
sucking problems
swllo\ving diffïctiliies
;isp ira t ion
potcntial for poor growtti
niirsing bottle caries
otitis niedia
drooling
Table 2: S u m r n q of i ~ t m rissociated ivith Mobius syndrome (Haderson 1939, Evans 1955. R e d & Griit 1957. ct al. 1985. Koroluk el al. l%Y. Gorlin et al. 1990. Kumar 19'30. Zuktlr IYYO. Sltx et üI. 199 1. and Chester & Zukcr I 992)
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Pathoeenesis
The pathogenesis of Mobius syndrome remains controversial. Necropsy repons sugsest that
at least four pathological explanations for the clinical signs of Mobius syndrome exist.
These include: ( 1 ) hypoplasia or absence of the central brain stem nuclei, (2) destructive
degeneration of the central brain stem nuclei, (3) peripheral nerve involvernent and, (4)
myopathy (MacDermot et al. 1990). Supporters of the ectodermal defect theory daim that
the defect is primarily located in the brain involving the sixth and seventh cranial nerve
nuclei, with secondary muscle dysplasia (Mobius 1888. Rainy & Fowler 1903. Spatz &
Ullrich 193 1. Fenyes 1937. Sprotkin et al. 19%. Van Allen & Blodi 1960). Supporters of
the rnesodennic defect theory daim that the defect is prirnarily due to muscle aplasia leading
to secondary nerve atrophy and state that the high incidence of rnusculoskeletal anomalies
support this theory (Richard 1953. Evans 1935. Wallis 1960. Pitner et al. 1965).
Pathological evidence is scarce and contlicting (Hanson et al. 1971). There are thineen
reponed autopsies of blobius syndrome cases (Heubner 1900. Rainy & Fowler 1903. Spatz
& Ullrich 1903, Fenyes 1937, Richter 1958, Riggs 1958, Wallis 1960, Pitner et al. 1965,
Hanissian et al. 1971, Sudanhan & Goldie 1985, and Iaradeh et al. 1996). According to
Pitner et al. ( 1965). as of 1965 there existed only four undisputed histological examinations
of Mobius syndrome. These examinations were done by Heubner (1900), Spatz & Ullrich
(1931), Wallis (1960), and Pitner et al. (1965). Pathological repons by Fenyes (1937) and
Riggs (1958) were challenged by Henderson (1939) and Richter (1958) who believed that
the facial paralysis represented intrapartum brain-stem hemorrhage rather than a tNe
congenital anomaly (Pitner et al. 1965). Hendenon (1939) and Richter (1958) also
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challenged Rainy & Fowler's (1903) case report stating that the obsewed facial paralysis
was due to trauma of both facial nerves by obstetrical forceps. Only autopsies reported by
Pitner et al. ( 1 965). Hanissian et al. ( 197 1). and Sudarshan & Goldie ( 1985) are known to
have examined both the brain and paralytic musculature (Table 3). Isolated examinations of
involved extra-ocular and facial muscles rvere reponed by Richards (1953). Yasuna &
Schlezinger ( 1955). Reed & Grant ( 1957). Van Allen Rr Blodi ( 1960). and Graham ( 1964).
but these authors had no opponunity to examine the brain (Pitner et al. 1965)
A completr review of the iiterature indicates that nuclear agenesis. with or without an intact
nrrve tmnk, intact nuclei with dysplastic or aplastic nerve trunk. or a pure muscle dysplasia
with an intact nerve tmnk and nucleus may be the pathogenetic rnechanism responsible for
Mobius syndrome (Hanissian et ai. 197 1) . Pitner et al. (1965) stated that the static course of
blobius syndrome is in itself indirect rvidence ajainst a degenerative process which would
be expected to continue into post-natal iife. Although Pitner et al. (1963) believed that
Mobius syndrome. in their report. was due to a primary dysplasia of the facial muscles. they
also stated that the histological observations of Heubner ( 1 WO), and Spatz & Ullrich ( 193 I ),
revealed a primary neuronal dysplasia. Mobius syndrome may have more than one etiology
and may involve the musculature derived from the branchial arches and/or the brain stem in
the same way that arthrogryposis can involve the musculature derived from somites and/or
the spinal cord (Pitner et al. 1965).
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Table 3- Necropsy Reports
Pitner et al. ( 1965)
imdeh et al. ( I996)
and
abnormal crriniai nerves III. VI. Vil. XI and XII
rcmtiining iirrvts lacking or Ljegtl~~er~trd
Ioircr part oitncdulla u~idcrrlcvtIopcd
rn histologicril changes in nuclei ofcrriniül ncrvrs III. IV. VI. and VI1
central nrrvous systrm rtpofled as nornial
d l cranitil nsrvss apprrired nomal
increast. in subcutanrous t'lit \\.ith dmost total absence o i tlw ilicilil muscles
crrinial nrnres III. IV. Vi ahsrnt
v e n thin lüciül nervrs
rn mürksd symrnstricd hypoplasia oi' the pons ruid rnedulla
0 no evidence of degentmion or dy splasiü o i hct craniul nervr: nuclri but fewèr
nucki in the right h?po$ossal nervr
0 prripherlil muscles not esamined
0 craniiil nswes VII. IV. VI. XII i ib~rnt
nurnbcr oi' neurons in al1 crlinial n w e nuclri were comparrible to u sirnilx
ape control
no rvidrncr of degrnerition t'oiind but the Ict't side ot' the toneue.
strrnocleidornüstoid. pectord. m d h c i d muscles displuyd adipose changes
simillir to Pimer et al.'s case ( 1965)
mild enlu-gernent of the vcntricular s'stati and a hypopliistic appezirrincr of
the Io\\.er brriin s t m
rnidline necrosis and ctilcitictition within thc tlaor o i the J~ ventricle ivith
mild @sis
nuclri of ci-mial nenres UI. IV. V. VI. and ViI intact. necrosis in the media1
longitudinal fasciculus ünd genu of the facial nenre
O no miçmscopic svidence of rnyopathy
O relative hjpoplrisia of riIl c m i a i ncnve nuclei at the mzdulla and pontinr
Ievrls
detailrd muscle esamination not p r r t ' o m d
o çerebral htmispheres normal but atrophie bnin stem
absent abducens nmfe ruid nudei
0 facial nrrvr a p p w r d strophic
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Etiology
The etiology of the suggested pathogeneses remains unclear. Environmental and heredi tary
mechanisms have been proposed (Table 4 a .b. c).
(i) fiiviru~rrnrnfnl
Mobius (1888) believed that the syndrome was due to a degeneration of the brain-stem
caused by a toxic insult, while Reed Rr Grant (1957) considered a developrnental defect of
the cranial nuclei and the posterior longitudinal bundle. Cranial nerves III. V (motor), VI,
VI!, and XII al1 lie in close proximity in the floor of the founh ventricle. A noxious
influence acting upon these nuclei, in such a restricted area, could account For many of the
manifestations of Mobius syndrome (Carr et al. 1997). Rubin ( 1 976) suggested
1 influences during the development of the fetus and listed "culprits" such as
, drugs, aicohol. smoking or poor placental placemenr. Rubin (1976) also
environmenta
bacteria, viri,
hypo thesized that a built-in hormonotrophic influence "_rone astray" could trigger an
ectodrrmal or mesodemal rnaldeveloprnent. Elsahy (1973) reported a case of Mobius
syndrome in which the mother took Thalidomide during her pregnancy. but Cwach et al.
(1997) described materna1 ingestion of Thalidomide as a separate etiology of congenital
bilateral facial paralysis. Bouwes-Bavinck & Weaver (1986) proposed that Mobius
syndrome results from an interruption of embryonic blood supply by premature regression,
obstruction, or disniption of the primary trigeminal arteries prior to the establishment of
sufficient blood supply for the brain stem and that the extent and nature of the associated
defects was dependent on the specific locations of vascular insufficiency. Harbord et al.
(1989) described a child with Mobius syndrome who also had unilateral cerebellar
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hypoplasia and suggested that the abnomalities were secondary to a vascular disruption
involving the basilar artery between 33 and 40 days of gestation. Lipson et al. (1990)
indicated signiticant events of pregnancy in eight of fifteen cases including hypothermia,
electric shock, failed abortion, previous uterine surgery, prolonged rupture of the
membranes, and alcohol abuse. The use of Misoprostol, as an unsuccessful attempt to
terminate pregnancv. has been associated with an increased risk of Mobius syndrome.
Pastuszak et al. ( 1998) identified 96 infants with Mobius syndrome born between 1990 and
1996 from 7 hospitals in Brazil. Forty-seven of the 96 rnothers (499'0). of infants born with
illobius syndrome. had used Misoprostol in the tirst trimester of pregnancy.
(ii) Hrredilory
Xccording to Baraitser (1977). Terntany & McKusick (1978) and Legum et al. ( 198 1).
Mobius syndrome has a heterojeneous etiology . Genetic studies have supponed the
heterogeneity concept in that both autosomal dominant (Fontanier & S pejer 193 5. Harrison
& Parker 1950. van der Wiel 1957, Krueger & Fredrich 1963, Hanissian et al. 1970, Masaki
197 1. Ziter et al. 1977. Stabile et al. 1984, iblacDermot et al. 1990) and recessive pedigrees
(Thomas 1898, Cadwalader 1922) have been reported. The recessive form of ilIobius
syndrome does not appear to be more severe than the dominant form (Legum et al. 1981).
An x-linked recessive trait has also been proposed by Joumel et al. (1989) who described
Mobius syndrome in two brothen and a male first cousin who were sons of sisters
(McKusick 1994). Mobius syndrome may be caused by mutant alleles at one or more gene
loci and the variable expressivity and decreased penetrance couid explain the Iack of clear
Mendelian inheritance patterns. Also, the association with other neuro-muscular and limb
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bud disorders may be explained by the pleiotropism of some of these genetic mutations
affecting the developrnent of certain mesodemal structures (Legum et al. 198 1 ).
Ziter et al. ( 1977) reported the clinical and cytogenic data of Mobius syndrome on seven
family members from three generations. Karyotype analysis revealed a uniform
chromosome abnorrnality in al1 clinically affected individuals. Giemsa banding revealed a
reciprocal translocation between chromosomes 1 and 13. The authors admined that their
pedigree size was srnall and that the observations did not resolve the controversy
surrounding the pathological basis underlying the iMobius syndrome. Donahue et al. (1993)
found an association between chromosomes 1 and 1 1 in one individual with Mobius
syndrome. Slee et al. (1996) presented a 2.5 year old child with Mobius syndrome with a
deletion of chromosome 13q and proposed that a pene for Mobius syndrome was located on,
or near. band q12.7 on chromosome 13, Kremer et al. (1996). described the performance
linkaje analysis in a large Dutch family with autosomal dominantly inherited Mobius
syndrome. These authors excluded Slee et ai's (1996) candidate region for Mobius
syndrome on l3q 12.2-q 13 and localized the gene to chromosome 3q2 1-22. indicating
jenetic heterogeneity. According to Nishikawa et al. ( 1997). almost al1 of Kremer et al.'s
(1996) subjects had unilateral Facial paralysis which diffus from the phenotypes described
by Ziter et al. (1977) and Slee et al. (1991). Nishikawa et a h (1997) report of a 15 month
old male with Mobius syndrome described a reciprocal translocation between the short am
of chromosomes 1 and the long arm of chromosome 2. The karyotypes of the parents were
nomal, indicating that the translocation was de rtovo. Despite the chromosome
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investigations on reponed cases o f Mobius syndrome, the chromosomal abnonnalities in
these individuais remains unclear.
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Table 4 a: Environmental causes of Miihiuu spdramc Mohius 18XX * clcgtncmtion ot'hmin-stcrii crtusrd by tosic insult Rcrd A Graril 1 'J57 r dcvclopnicntrtl dtiïtxt in crdnitrl nuclcii and posicnor
Iongitmiiniil hiindlc. criiiscd by nosioiis inllucii~rs EIsdiy 1 Y73 * llialicloini~l~. during prtgiiaiic y Rubin 1976 * ciivironnirntd intlucnces during drvclopmrrit o i the ktus
{hacteriü. vin. aicohol. smoking. poor placcntiil plriccmrlnt ) BOUN es-Bav irick dk Wwvrr I 986 * interruption of embnonic bloocl suppl y b y premature regrrssion.
obstruction. or di sruption of the primüry trigeminal artcrics prior to establishment ol' siitticient blood suppl! for the bmin
Hrirbord ct al. iLHY vcisculrir disniption Lipson clt ai. ! LNO sigtiific:int txsnts JuRng pregnitnc?. such ris hpxhemiiri.
&ctric shock. L'tiilcd ribort~on. prrtViolis utcrine surgep. proIorigd nipturt. o i mrmbrmes. B I I ~ alcohd abuse
Pristiisztik cf d. I 998 * use ot'h.lisopro~fol in tint trirnestcr oi'pregnrinc!
Table 4 h: Cenctic cases of hliibius syndrome
imilial Iiistcirirs in 3 crises Sh cast.s in 6 grnerdtiotis 3 grnerations ol 'aifectd mmhers mo~iozygot ir: hvtns 3 c.3st.s in 2 grneration 7 uses in 3 2cnt.mtions -7 cascs in one tiniily inothcr KL son. mothcr's itiatcrn~l aunt ml sou
S-Linked Joumri et al. 198Y 2 brothers & male cousin (sons oisistrrs)
Table 1 c: Proposed location of gene for Miibius syndrome Zitrr et al. I Y 7 7 recipmçal trrinslocation betwesn chromosomr 1 k 13 Slse et al. 199 1 * 13q12.2 Donahue et al. 1993 recipmcal ~rmslocrition brnveen chromosome 1 k I I kernr r et al. t 996 -3 (11 bq22 Nishikma et ai. t 997 * reciprocd rmsiocrition bchveen chromosome 1 2
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[
According to Kumar (1990). malformations of the orofacial complex rnay be present in
Mobius syndrome and their presence may aid in the diagnosing the syndrome. Detailed
descriptions of the craniofacial rnorphology and malformations of the orofacial cornplex are
extrernely rare despite their inclusion in the diagnostic criteria. The craniohcial morphology
can be described in terms of nerve and muscle involvement, soft tissue assessment, facial
anomalies. oral manitèstations. skeletal morphology. and dental malocclusions.
(i) Nerva-
The cranial nerves affected in blobius syndrome include cranial nerves III, IV, V (motor),
VI. VII, VIII, LX. .Y. XI, and XII. Cranial nerve VI1 is always affected to some degree, with
cranial nerve VI beins the second most cornmoniy affected (Kumar 1990, Carr et al. 1997).
According to von Zimrnerman (1966), taste and lacrimation are usually normal. The
hypoglossal nerve is the third most frequently involved nerve and is affected in
approxirnately 75% of the cases (Van Allen and Blodi 1960). The extent of the cranial nerve
involvement determines the clinical manifestations observed (Table 5). The incidence of
cranial nerve involvement from Engler et al.'s (1979) review of 106 cases and Carr et A.'s
(1997) review of 156 reported cases is listed in Table 6 and 7 respectively.
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17
Table 5: Sumrnary of Crinial nenes and associrited funcrions (Liebgott 1986. Wilson-Pauwels et al. 1988)
N e ~ e .. . ' 1; Fùnction .. . , . - .
. - r - Olfacton (1) 1 Scnsc of siiicll
1 Parxynpalhetic supply to cilia? and pupillaq constrictor niuscles Trochlcar (IV) * [ r Motor supply to supenor oblique Trigeniinal (V) * 1 r Moior to niiiscles of mastication (V3) tensor tynipani. tensor palati.
- . 1
1 mierior belly of digastric. and rnyloh~oid muscle
Optic ( I I ) Oculoniotor (Ill) *
1 r Estcroceptive: skin of ihc bcc. oral :uid nasal iiiucosa. iiieningcs. ;ind
' Vision Motor to al1 csu-aocular rtiusclcs csccpt supenor oblique and lateral recrus
- Pmqrnpathetic nipply to ail glands of the head escept the parotid and intcgunientriry glands
Abduccns ( IV) * Facial (VII)*
9 Proprioccpti\~c: pcriodontiurii. pallitil1 niucosri. niusclcs of niristicrition. and teiiiporoiiiiindibulrirjoint Motor to Iiitcrril rcctus nitisclc
r Motor to niiiscles of Fxiril expression. platymi. stylohyoid. posterior bclly of digastric. and siapedius muscle
(LW * 1 r Parasympathetic supply to parotid gland
Vsstibulocochlear (VIII) * Glossop h;in-ngeal
1 a Sensoq recepton in die skin of the riuncle. iiiiicous nienibnne of
- Cutanco~is rcceptors in conclia of aiiriclc œ Triste rmtcrior Zi3 of tonguc 0 Balancc
Hcriring - blotor to sty lophaqngcus tnusck
1 postcrior l/3 of tongiic. pliiu)ns and rniddle ur
1 supenor. niiddle. infenor constrictor n~usclcs of the pliüqms. Vagis (‘O*
1 palatoph;uygeiis. levator palaii. palatoglosnis. and inuinsic muscles of
œ Tastc postcrior 213 of totig~~c œ Supplies ; i l1 ~ t n i i t ~ d niusclc supplicd by the branches of the ~ a g m n e n c
1 r Sniooth iiiuscle of rlic broncliinl trce. hcm. stomacli. srniil1 and large intestine up [O die lcft colic llesurc. sccrctornotor fibcrs to glands of the respintory and digestive systems
1 r Senson reccptors in the meninges of the postcnor manial fossa. skin of
1 the estenial auditory nieÿtus. mucous membrane of the 1-nx and
1 viscemrecepton of the lhoncic and abdoniinal riscen
pliuyns- pa l a top l~~ngeus nluscle. levator pa1ati muscle. palatoglossus muscle. and intrinsic muscles of the I q n s
Accessory (XI)* œ Taste receptor arowid the inlet of the l w n s and epiglottis œ Cranial portion: superior. middle. inferior constrictor muscle of the
palatoglossus Hypoglossal (XII)*
Spinal portion: stemocleidotnastoid and tnpezius muscle Motor to inuinsic and esuinsic muscles of the tangue escept
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Table 6: Engler et al.'s (1979) distribuiion of cranial nenle pafsies in 1116 rcportcd cases of Mobius syndrome
Cranial Nerve Palsies C m i a l Nervc VI1
Cranid Ncrvt. VI Cranid Ncrvc 111 Cranid Nervc XII
Cranid Nerve VI1 unil3tcd Cranid Nene VI bilaterd Cranial Nerve VI u n i l a t d
Percent of Reported Cases 10094,
6 i '4
23%
22%
Cranid Nervc: IX Cranial Nerve XII Cmid Nerve X C m i a l Nervc I I I Cranid Nerve IV Cranid Nerve V
Table 7: C m et sl.'s (1997) distribution of cnnial ncnc palsies in 186 rcponed crises of Mobius syndroiiie
(ii) hhrsc./e.s
a) Muscles of facial expression
The muscles of facial expression are derived from the second branchial arch and are
supplied by the facial nerve (cranial nerve MI). The muscles of facial expression are found
within the superficial fascia around the facial orifices and have two basic functions: 1 )
dilators and sphincters controlling the openings of the orifices, and 2) movers of the
overlying skin enabling various facial expressions to be perfoned (Liebgott 1986). The
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elevator of the upper eyelid and the muscles of mastication are the only muscles of the face
that are not innervated by the seventh cranial nerve. (Rubin 1976) The muscles around the
mouth lips, cheek. chin. nose. eye, and forehead and their associated actions are listed in
Table 8.
According to Kumar ( 1990). complete or partial congenital facial nerve paralysis is essential
for the diagosis of Mobius syndrome. The facial paralysis is non-progressive (Mitter et al.
1983) and may be unilateral. but is more typically bilateral (Kumar 1990). The incidence of
bilateral and unilateral facial paralysis was found to be 85% and 1596 respectively in Carr et
al.'s (1997) review of 186 reponed cases in the literature. The lower pan of the face is
usually less affected than the upper part if the paralysis is incornplete (Henderson 1939.
Edgenon et al. 1975). Xccording to Henderson (1939), the frontalis muscles are most
constantly paralyzed. whereas the muscles which draw the corners of the mouth ouward and
downward. including the platysmae. mav be spared. The peri-orbital muscles are usually
cornpleteiy affected. but may occasionally contain a few tiring fibers.
Electromyography results reponed by Hellstrorn ( 1949). Van Allen & Blodi ( 1960). von
Zimrnerman ( 1966). McHugh et al. (1969). Olsen et al. ( 1970). Masaki (1 97 1). and lamal et
al. (1988) have shown little if any evidence of electrical activity in the facial muscles.
b) Muscles of mastication
The muscles of mastication are derived €rom the first branchial arch and are supplied by the
motor component of the trigeminal nerve. The muscles of mastication are comprised of four
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main pairs of muscles attached to the mandible, as well as accessory muscles. These muscles
are responsible for elevating, protruding, retruding and moving the rnandible laterally
(Liebgott 1986). The muscles of mastication and their associated actions are listed in Table
9.
..MUSClee:.-- ---.---- . - --+ > . ,' . . A&On,--f-f. - . . --.. - . -.- CI -- ... < . .-W. .-. -*. . . a. . \ .- -. . ... . .. - <-..-_ . * ., .+ % , .' " - ,,.;. - . . . , . . . + .
Obicularis oris compresses lips against anterior teeth. closes niouth. prouudes lips 1
Dcpressor anguli oris 1 depresses angle of mouth 1 1
Levator anguli oris 1 elevatcs angle of mouth I 1
Zygomaticus m j o r 1 drarvs angle of rnouth up and back 1 1 Zygomaticus minor
I
1 cir-ws angle of mouth up I 1
Risorius 1 draws mgle of mouth latenlly 1 1
Levator labii mpcnoris 1 elevates uppcr lip. flares nosuil 1 I
Depressor labii inferions 1 depresses lotver lip 1 I
Buccinator 1 compresses dieek against rnolar teeth. sucking and blowing 1 1
klentalis ( pucken skin of chin. proinides lower lip 1 1
Nasalis 1 cornpressor n m : compresses. dihtor nÿres: flares nosiril 1 1
Orbiculriris ocitli ( orbital: closes eye forcefully. palpcbnl: closcs eye gently 1 1 Procrnis 1 u i i s e r s e rvrinkling of bridge of nose I
Comgator 1 ~rrtical wrinkling of bridge of nose
Fronirilis 1 pulls scalp up and bnck 1 Ysma Pht- 1 tenses skin of neck. ciids in depression of niandible
Table 8: bluscles of the hcc inncnated by crmial nen7e VI1 ruid associated actions (Liebgott 1986)
1 Mssseter 1 elmation. prouusion. remsion and ipsilateral excursions 1 1
Temporalis 1 elevation. retrusion and ipsilateral escursions
1 Medial Pterygoid 1 elmation. pminision and contralateral escunions 1 1
Lateral Ptelgoid 1 pmtrusion. depression and conm1atenl excursions 1 Table 9: Muscies of mastication innervrited by cranilil neme (V) and rtssociated actions (Liebgott 1986)
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(iii) Sofi Îis~mes
Individuals with Mobius syndrome are described as having a high nasal bridge (Reed &
Grant 1957) which extends down to include the nasal tip resulting in a midface prominence
(Gorlin et al. 1990). The prominent upper lip and prominent and everied lower lip is a
striking feature in adults (Henderson 1939). Lip incompetency has been reported by Chester
& Zuker (1992). Whether the lip incornpetency is associated with excessive incisor
protrusion, or an increased vertical face height growth. has not been investigated (Figure 1 a,
1 b).
Evans ( 1 955), Reed & Grant ( 1957), Elsahy ( 1973). Sugarman et al. ( 1973). Federman et al.
(1975). Wedgwood (19781, Gutman et al. ( 1973). Meyerson & Foushee ( 1 978). Hopper et
al. ( 1 985), Legum et al. ( 198 l) , Parker et al. ( 195 1 ), Sudarshan et al. ( 1985). Rubin ( 1986).
Kuhn (1988). Harbord et al. ( 1989). Joumel et al. ( 1989). Koroluk et al. ( 1989). Slee et al.
(199 1 ), Donahue et al. ( 1993), Jaradeh et al. ( 1993). and Sherer & SpafFord ( 1994) reported
a micrognathic appearance of the mandible. but these were soft tissue assessments.
(iv) Fac*icd A,iomo/ies
Extemal ear defomities. hypenelorism, and epicanthic folds have been reponed by Gorlin
et al. ( 1990).
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Figure la: Mobius syndrome - frontal vietv Figure Lb: Mobius syndrome - profile view
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Ornl Mariifk-infiorls
Henderson (1939) listed bifid uvulas as an associated feature of the syndrome, but this
feature was only observed in 2 of the 61 cases he reviewed. Cleft palates were reported by
Meyerson & Foushee ( 1978)- Bergstrom et al. ( 198 1 ), Sudarshan & Goldie ( l985), Donahue
et al. ( 1993). and Jaradeh et a1.(1996). Microstomia was reported by Meyerson & Foushee
( I978). Gorlin et al. ( 1986) and Rizos et al. ( 1998).
Henderson ( 1939). Meyerson & Foushee ( 1978). Slee et al. ( 199 l ) , and Sherer & Spafford
(1994) observed high arched palates. Slee et al. ( 1990) observed a small tonsue with
hypoglossal weakness. while Sherer & Spafford ( 1994) observed a normally proportioned
tongue. The extent of rnaxillary constriction and the relationship to the presence or extent of
tongue hypoplasia or paralysis h a not been investigated.
Speech. feeding and swallowing difficuities rnay occur as a result of hypoglossal (XII).
trigeminal (V). glossopharyngeal (IX) and vagus (X) nerve involvement. Unilateral tongue
hypoplasia is more frequent (Evans 1955), but bilateral tongue hypoplasia c m occur (Evans
1955, Reed & Grant 1957, Hanissian et al. 1970). Speech may be defective due to the
involvement of the lips, tongue, palate and larynx (Evans 1955). According to Chester &
Zuker (1992), speech is always affected to some degree. Patients are usually unable to
produce bilabial sounds due to their lip incompetency. The hypoglossal nerve involvement
with resultant tongue hypoplasia leads to restricted tongue rnovement and affects vowel
sounds. Speech may be affected by velopharyngeal incornpetence caused by
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glossopharyngeal paralysis alone or in combination with paralysis of the vagus and
accessory nerves. Paralysis of the tensor veli palatini muscle may lead to chronic otitis
media and further affect speech development. The incidence of mental retardation is
approximately lO?/o. but is typically overestimated due to the child's lack of facial
expression and poor speech (Chester & Zuker 1992). Sucking and feeding problems usually
persist into childhood. Affected children may be bottle fed to a later than normal ase due to
their feeding and sucking difticulties, and nursing bottle caries may result (Koroluk et al.
1989). Poor growth may occur due to poor feeding during the first years of life (Godin et al.
1990).
(vi) Skr le ta/ C7muiofncic~l iL101pholu~
The craniofacial rnorphology associated with Mobius syndrome has not been established via
controlled cephalornetric studies. The inclusion of micrognathia has persisted although this
inclusion has not been substantiated by the literature. Also. the inclusion of micrognathia has
been based on clinical soft tissue examinations rather than cephalometric skeletal analyses,
and micrognathia was most often reponed from soft tissue profile assessrnents of younger
individuais.
The etiology of the reported micrognathia has not been investigated although Smith (1976)
and Jones (1988) reported that the observed micrognathia in Mobius syndrome was not a
primas, dysmorphic feature but rather secondary tu a neurological defect in the early
movement of the mandibte in utero.
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Micrognathia has been listed as an associated feature of Mobius syndrome by the following
authors (Table 10):
I I 1 occurs. but Ins frcquentl! hm 0 t h 1
Reîierence +- -7 :: - .--
not referenced
1 ~ederman et al.
; Mierognatbia in Mabius Syndrome. .: :, * micrognathia is an momaly which
:- Apthov: . - -.*' A !.bar "
Pitner et al.
Gutman et al.
Reed & Grmt
* States that nian! riuthors have dcscribed patients with mmdibuar
1957
1965
t 973
* retrognülhiri is an lissocirited rinonialy I tg7 j 1 inMdbiusswdroriie
not refcrcnced
Godin et al. 1964
associated anomalies rnicrognathia is a deformity associated with Mobius syndronie
* the underde\.elopnienr of Lfic nirindible could be relittcd to tlic parcsis
not referenccd
not refcrenced
Banitser
Meyerson & Foushee
Sugarmrin & Stark
Wedgwood
1 1 1 Mobius svndrome 1
1977
Engler et 31.
1978
1973
1978
defomiities nich as micrognathia * micrognathia is an associated feature
of Mobius svndrome
1970
/ Bergstrorn ci al. * niicropatliiri is an mociatcd t'cmre 1 14" 1 of Mdbius iyndronie
Table 10: Statements of micrognathia in Mobius syndrome and respective references
not refercnced
* mandibular hypogencsis is a fcaturc of Mobius syndrome
* micrognaihia is an associatcd abnorniality in i'vlobius syndrome
* micrognathia is a clinical
Gorlin et al. 1976
Gorlin et al. 1976
not referenced
Henderson 1939 manifestation in Mobius syndrome
* micrognathia is an associrited defcct in
Hopper et al.
Bccrbowcr et al.
Jones
Gorlin et al.
Kurnar
Sherer & Spafford
Kremer et al.
Rizos et al.
not rcfcrcnced
* micrognathia is an associated rraniofacisl anomaly in hdobius syndrome
* micrognatiiia is an associatcd fcature of Mobius syndrome
* micrognathia is an associated feature of Mobius syndrome
* maridible is frequenily mildly to moder~tely h)popiastic
* rnicrognathia is a malformation of the orofacial structure which may be present and aid in the diagnosis of Mobius qmdrome
* Mobius syndrome is frequently acconipanied by micrognathia
* micrognathirt and other mriiformations of the jaws as orofacial maiformations present in Mobius syndronie
* micrognathia is a sign associated with Mobius svndrome
1985
1986
1988
1990
1990
1994
1996
1998
Gorlin et al. 1976
Pitner et al. 1965
not rcfcrenced
Evans 1955. Reed & Grant 1957 Gorlin et al. 1 YS6
Meyerson & Foushee 1978. Jones 1988. Mobius 1888. Henderson 1939. Richards 1953. Bmitser 1977. Kurnar 1990. MacDermot et ai. 1990 Sherer & Spafford 1994
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Aithough Henderson (1939) has been cited as a reference for the presence of rnicrognathia
in individuals with Mobius syndrome, there was no description of the mandible in his
review of 6 1 case reports.
Godin et al. ( 1964, 1976. 1986, 1990) have been frequently cited as a reference for the
inclusion of micrognathia as a craniofacial manifestation of Mobius syndrome. They
described the mandible as mildly to moderately hypoplastic. Godin et al. (1990) cited Evans
(1955) and Reed & Grant (1957) as a reference for this latter statement. Interestingly
enough, Reed & Grant (1957) reponed micrognathia in the three cases they described and
stated that microjnathia was a developmental anomaly which occurred less frequently in
individuals with Mobius syndrome. Evans ( 1955) stated that micrognathia was not regarded
as a constituent of Mobius syndrome. Five of nine cases reponed by Evans (1955) were
described as having micrognathia at an early are. Threr of these five cases of micrognathia
showed improved growth of the mandible as the children matured. Evans (1955) felt that
significant mandibular growth was evident resulting in a "less obvious" degree of
mandibular hypoplasia. He also stated that mandibular hypoplasia might be expected to
occur with hypoplasia of the muscles, but that a coincidence of hypomandibulism may have
exis ted.
A review of literature of 186 case repons from 1888 to 1998 by this author (Table 11)
showed that micrognathia or retrognathia was reponed in 75 of the 186 reponed cases
(13.4%). Eighteen of the 25 subjects were exarnined at a young age (Table 12).
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Table 11: Cmniofacial tisscssnients of 186 cises of Mobius syndrome reportcd in the litenturc
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1 1988 F L 1989 F 7Jno 1 1989 \i habu 1 19R9 F 45 nio
\I son 1991 2-
tr 1932 F vrr
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The normal fetal mandible at rest occupies a relative posterior or distal position and a
considerable increase in size is seen between fetal life and three years of age. Mandibular
yrowth then increases at a slow rate until adulthood (Scott 1961). The inclusion of
micrognathia, as an associated feature of Mobius syndrome, may be based on observations
of normal distally positioned mandibles.
1 Evans 1 Evans
Evans
--
Rccd & Grant Reed & Grant Sugman et al. Federman et al. Meyerson & Foushee Mcyerson & Foushee Leguni
loumel ct al.
.Year -.' 1
1955 1955
Gender b!
1950
1955
1957 1957
1973
b1 F
1975 1978 1978 1981
1994 I F 1 prenatal 1 inicrognathia
Age 10 weeks
M bl F F M
Table 12: Reports of micrognathic or retrognathic mandibles in Young individuals with Mobius syndrome fiom 1888 - 1998. 18 of 25 reports of micrognathia in 186 case rcports of Mobius syndrome
Description of theMandiMe . ' ; ' . micrognrithia
4.5 years LO weeks
M M M F
1
Engler et al. ( 1979) listed micrognathia as an associated feature of Mobius syndrome. They
reviewed 106 cases reponed by Fontanier et al. ( 1 939 , Henderson (1 939), Hicks ( 1 943).
Danis (1 945). Murphey et al. ( 1947), Van Buskirk ( 195 1 ), Stansbury ( 1952). Richards
(1953), Evans (1959, Nisenson (1955), Sprofkin et al. ( 1956), Reed & Grant (1957), Van
micrognatliia micro grtathia
J weeks 5 months 3 years 2.5 yc,m 5 y e m
nc\t8born 45 niontlis baby 2.5 !.en 3 v e m
1985
1989
1989
1991
3
- micrognathia micrognathia moderate micrognathia ~narked micrognathia micrognaiiiic
3 y e m
2 years 6 y e m babv -
micrognilthic small mandible microreirognnthia micrognathic micro-gnathic & reuognathic
? F kI F F
retrognathic 4
mi1d micrognrithia mild micrognaîhia
, modemtely micrognathic
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Allen & Blodi (1960), Masaki ( 197 1). and Becker-Christensen & Lund (1 974). Of the 106
cases of Mobius syndrome, 6% (approxirnately 5 cases) had micrognathia. These five cases
were those described by Evans ( 1955) and Reed & Grant ( 1957).
Sherer & Spafford's (1994) case report consisted of a prenatal sonographic examination of a
fetus with Mobius syndrome. The sonographic examination revealed micrognathia. The
infant also had respiratory difficulties which was thought to be secondary to the
micrognathia.
Except the three cases reponed by Briggs (1965) Gutman et al. (1973). and Rizos et al.
(1998). assessments of mandibular position and size were performed clinically without
radioçraphic analyses. Mcrognathia continues to be listed as an associated feature of
Mobius syndrome despite the lack of controlled clinical and radiogaphic studies. Analyses
of the actual size and position of the mavilla and mandible are currently lacking. Clinical
observations of "micrognathic" mandibles rnay be misleading, especially for examiners who
are not familiar with the potential variation in position and size of the mandible. When the
skeletal components of a Class II malocclusion are measured and assessed on cephalometric
radiographs, one may observe: (1) a micrognathic or retrognathic rnandible with a normal
size and/or positioned rnaxilla, (2) a normal sized and normally positioned mandible with a
proynathic mailla, (3) a normal shed mandible rotated downwards and backwards or, (4) a
combination of the above (Woodside 1976) (Figure 2).
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Figure 2: Skrletal Components of Clxs I I klalocciusions (A) micrognathic or retrognathic mandible. (B) prognathic midface. (C) normal simd mandible rotated downward and backwrud, (D) Combination. Adripted from Woodside: Ccphalometnc Roentgenognphy. p 6. 1976.
Class III skeletal patterns have been described by Thomas ( 1898). Briggs (1965) and
Chester & Zuker ( 1992). Thomas ( 1898) described a 19 year old male with a prognathic
rnandible and a negative overjet who undenvent a bilateral mandibular osteotomy in order to
improve the patients lip incompetency. Briggs ( 1965). described an eight year old female
with a "de finite skeletal Class III" malocclusion. Measurements to assess the vertical
dimension were not included in Briçgs' ( 1 965) cephalometric analysis.
Due to ( 1 ) the lack of controlied cephalometric studies. (2) the inclusion of micrognathia
being based on soft tissue assessments. and (3) micrognathia being reported more frequently
in newboms, infants and young children, furher comprehensive cephalometric studies are
required.
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vii) Dr n t d Mai m.*c/usion
Various dental malocclusions in individuals with Mcbius syndrome have been reported.
Case reports by Wedgwood (1978) and Gutman et ai. ( 1973) described Class II
malocclusions, whereas Briggs (1965) described an eight year old female with an Angle
Class I malocclusion on a Class 1 to mild Class 111 skeletai base. Chester & Zuker (1992),
described two cases of Mobius syndrome with Class I I I malocclusions and stated that this
type of malocclusion was not usuaily associated with blobius syndrome. Maxillary incisor
prominence and linguoversion of the rnandibular incisors were observed in Federman and
Stoopack's (1975) case repon. while an anterior crossbite was seen in Briggs's case report
( 1965) F o g ~ ( 1980) described a 17 year old kmale with excellent occlusion. while Rizos et
al. (1998) described a 17 year old fernale who had multiple congenitally missing primary
teeth and was also congenitally missing the Following teeth: 1 . 1 , 1 2, 1.3, 3.1, 3 2, 4.1, 4.2.
1.3. 1.8. She also had a Class II molar relationship on the right and a Class III molar
relationship on the left along with a 12 mm anterior open bite and bilateral posterior
crossbites.
Other Fentures
Oczrlar rVercv Palsies
The ocular involvement of Mobius syndrome includes bilateral or unilateral ocular nerve
palsies. The abducens nerve (VI) i s the most commonly involved ocular nerve with the
trochlear (IV) and oculomotor (III) nerves being affected less frequently (Kumar 1990).
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Lim b Mai furmat iom
Limb malformations such as syndactyly. brachydactyly, absent digits. hypoplasia of digits,
and talipes are often present in individuals with Mobius syndrome (Henderson 1939.
Richards 1953). In Engler et a l . 3 ( 1979) review of 106 cases of Mobius syndrome, 28%
had associated limb anomalies and according to Temtany et al. (1978). club foot is the most
common limb malformation with the Requency being approximately 33%. According to
Baraitser (1977). limb malformations must be included in the diagnostic criteria of Mobius
syndrome. Based on his observations in 15 subjects, along with 50 subjects previously
reponed in the literature. Baraitser ( 1977) cnncluded that when the definition of Mobius
syndrome included skeletal malformations. the risk of the offspring having similar
characteristics was approximately 2%. According to MacDermot et al. (1990). a higher
recurrence risk of 25941 to 30% seems reasonable when skeletal defects are absent.
Orhrr il~l~i.scrrio.~~ke/ti~~~/ .-lrror~in/ie.s
According CO Kumar (1990). anomalies of the niusculoskeletal system such as Klippel-Fei1
anomaly, absence of the sternal head of the Pectoralis muscle. rib defects, and branchial
muscle defects may be associated with Mobius syndrome. Poland syndrome has also been
associated wi th Mobius syndrome. This corn bination has been referred to as Poland-Mobius
syndrome (Hopper et al. 1985). Poland-Mobius syndrome is estimated to have a prevalence
of 1:500.000 (Hemnann et al. 1976) and is manifested by bilateral paralysis of the sixth and
seventh cranial nerves. absence of the Pectoralis major muscle. and ipsilateral hand and digit
anomalies (Hopper et al. 1985).
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Radio~ra~hic Findines
According to Beerbower et al. (1986). CT scans are useful in evaluating the features of
Mobius syndrome and may be used to document any malformations that indicate a more
extensive CNS process not clinically evident in the newborn. CT scans can aid in the
identification of concomitant brain malformations and exclude possible treatable or
progressive disorders such as infection. hemorrhage. trauma. hydrocephalus. or tumors that
could mimic Mobius syndrome. Most patients with blobius syndrome have normal CT scans
except for the media1 gaze of the eye as a result of' the lateral rectus paralysis. One would
expect no characteristic brain findings with CT scans given that the fundamental
pathological lesion remains unknown (Kuhn 1988).
According to Kuhn ( l988), congenital anomalies of the branchial musculature and
extremities including talipes equinovanis. digital anomalies. congenital hip dislocations,
unilateral hypoplasia or aplasia of the pectoralis musculature, S-shaped scoliosis. and
anhrogryposis have been observed radiographicall y, but the spectrum of radiological
findings in EvIobius syndrome has never been iilustrated
Cephalometric analysis results in a quantatative examination of craniofacial growth and
development (Steiner 1953). Although lateral cephalogams were taken on the three cases
reported by Briggs (1965), Gutman et al. (1973), and Rizos et al. (1998), there are no
controlled cephalometric studies describing the craniofacial morphology of individuals with
Mobius syndrome. Briggs observed a "definite skeletal Class III" malocclusion while
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Gutman et al. ( 1973) described a micrognathic rnandible. Rizos et al. (1998) described a
Class II skeletal apical base relationship with a hyperdivergent growth pattern. Gutman et al.
( 1973) also observed a rather small appearing sella turcica with an enlarged anterior and
posterior clinoid process partially connecting the saddle. The Findings described from the
skull series performed on Sugarman & Stark's case (1973) showed an average size cranial
vault with the sella turcica having a normal appearance and the mandibular angles were
described as "quite obtuse". Although ail three subjects reponed by Reed & Grant ( 1957)
were clinicall y described as having micrognathia, the skull radiographs were described as
normal.
Sureical Interventions
i) Oi'r l~o.~~inthi~~ S ~ q q v
Thomas ( 1898) described bilateral rnandibular osteotomies to correct a prognathic rnandible
while Gutman et al. (1973) described an individual who underwent an Obwegeser sagittal
osteotomy with anterior repositioning of the mandible and chin to correct a retrognathic
mandible. Gutman et al. (1973) described an individual with Mobius syndrome with the
muscle of mastication also being affected. Although the individual described by Gutman et
al. (1973) had an "elongated face", mavillary impaction was not performed. The incidence
of orthognathic surgery and the incidence of surgical relapse due to the paralytic
musculature, is unknown.
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ii) Sirraen> for Rranirnntioii
Facial reanimation has always been an important issue with Mobius syndrome. Early
corrective procedures for paresis of the facial muscles included static suspensions of the lips
and nasolabial folds. Materials used included fascia from the thigh. srainless steel strips. and
silicone ribbon. The surgical results were static and immobile and had minimal effect on the
patients blank. fixed facial expression (Rubin 1976).
In 1933. Gilles transplanted the anterior portions of the temporalis muscle to activate the
nasolabial folds and the corners of the mouth. In 1952, McLaughlin detached the coronoid
process of the mandible and left the bones Fastened to the temporalis tendon. .A sling of
facia lata was placed around the lips in order to sirnulate an orbicularis oris muscle. This
sling was then insened into a hole in the coronoid process and was in mm elevated by the
entire temporalis muscle. McLaughlin's technique was prirnarily used in unilateral Facial
paralysis (Rubin 1976).
In 1 976. Rub in described bilateral tem poralis transplantation. with tem poralis facia as added
tendons. to activate the cheeks. upper lips. nasolabial folds and eyelids. Rubin's (1976)
procedure could only be used if the fifth nerve was present. Later, Rubin et al. (1986)
described his state of the art reanimation technique which included shonening or plication of
the weakened facial muscle and replacing individual degenerated muscles with strips of
temporalis, rnasseter and frontalis muscle. According to Rubin et al. (1986), the expectations
for obtaining good results with this technique were reasonable, but total reanimation
remained impossible.
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Edgerton et al. (1975) described two surgicai techniques used for reanimation in the Mobius
syndrome patient. Edgerton et al. ( 1975) used muscle transfers from either the functionin~
platysrna muscle or the ternporalis muscle. Edgenon et al. (1975) believed that when
Mobius syndrome spared the platysma muscle. strong consideration should be given to using
this valuable tme "mirnetic" muscle.
Although facial movernents were achieved through local muscle transfer procedures such as
those postulated by Rubin et al. ( 1986). insufficient excursions with these techniques were
noted (Zuker Rr Manktelow 1989). .Accordin_r to O'Brien et al. (1980) and Tolhurst & Bos
(1982). the seventh nerve is the only nerve which provides the desired spontaneity of
activity with emotional expression. Zuker ( 1990). described a stage-setting cross-face nerve
graft in unilateral facial paralysis in order to provide seventh neme input to the affected side.
Innervation by a non-seventh motor nerve. such es the hypoglossal nerve (XII) or the motor
nerve (V) to the masseter muscle. was used in bilateral facial paralysis therefore spontaneous
and synchronous activity, along with ernotional expression of the transplant muscle, was not
possible. Intricate and complex movernents of the upper lip and commisure was not possible
with the utilization of a single muscle but asymmetries at rest were corrected by positioning
the muscles under appropriate tension. Synchronous and spontaneous movement of the
upper lip and commisure in the desired direction was also achieved (Zuker 1990). Although
absolute symmetry could not be expected. nor fine variations in expression, the muscle
activity resulted in a symmetrical srnile.
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Zuker and Manktelow (1989) performed vascularized muscle transplantation in seven
patients with blobius syndrome (Figure 3. 4). Five patients had bilateral facial paralysis and
two patients had unilateral facial paralysis. resulting in twelve transplant procedures. A
single-fascicle functioning motor unit was used in al1 subjects. A gracilis muscle was used in
eleven transplants and a segment of the latissimus dorsi muscle was used in one transplant.
The facial vesse1 was used for revascularization in al1 twelve subjects. Reinnervation was via
the hypoglossal nerve in nine transplants, the rnotor nerve to the masseter muscle in two
transplants and a transfacial nerve graft in one transplant. According to the authors, eleven
of the twelve transplant areas demonstrated sufficient movernent to meet their initial surgical
expectations and muscle transplantation offered excellent potential for smile reconstruction
and improved social habilitation for individuals with Mobius syndrome (Figure Sa, 5b. 6%
6b).
Facial reanimation surgrry is ideally performed at age 5-6 years for psychosocial concerns
(Zuker 1990) An evaluation of the potential improvements in craniofacial qowth and
development is required if controlled cephalometric studies confirm an altered craniofacial
morphoiogy in individuals with Mobius syndrome.
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Figure 3: Flap prior to placement of graciiis muscle
Figure 4: Superficial location of gracilis muscle
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Figure Sb: MSbitis syidrome - m i l e a tkr right ~ ind Ieti gncilis transftr
Figure 6a: Mdbius syndrome - smile aArr right Figure 6b: Mdbius syndrome - srnile atler righr and leR gncilis tnnsfer
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Conclusions
Mobius syndrome was first reported by Mobius in 1888 and approximately 200 cases have
since been reponed. Many questions regarding the syndrome remain unanswered. The
pathogenesis and the etiology of the syndrome continue to be debated. Autopsies have
indicated that the primary lesion may be of both ectodermic or mesodermic origin and,
environmental. as well as familial cases. have been reponed. Chrornoson~al studies continue
to search for the Mobius syndrome gene but differing opinions exist regarding its location.
The dental and orthodontic literature regarding Mobius syndrome is extremely rare. The
maloccIusion associated with Mobius syndrome has not yet been investigated and no
controlled cephalometric studies have been conducted in order to assess the skeietal
craniofacial morpholo~y The inclusion of micrornathia and midface prominence has been
based on anecdotal evidence based on soft tissue assessments.
Facial reanimation continues to be performed with expected success. but the potential
benefits for improved facial growth have not been assessed. Studies to compare the
craniofacial skeletal rnorphology OP non-reanimated to reanimated cases are indicated if
facial growth and developrnent proves to be affected by the paralysis involved in Mobius
syndrome.
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STATEMENT OF THE PROBLEM
Mobius syndrome is a form of congenital paralysis of the muscles of facial expression due to
the involvement of the seventh cranial nerve. I t may also involve cranial nenies Ill, IV, V.
VI, VIII, IX, X, Xi, XII and their associated functions (Kumar 1990, Carr et al. 1997). There
are approximately 200 cases of Mobius syndrome reported in the literature (MacDennot et
al. 1990) but there have been no studies to determine the craniofacial skeletal morphologv.
Abnormalities such as micrognathia and midface prominence have been claimed as Features
of Mobius syndrome (Engler et al. 1979. Gorlin et al. 1990. Kurnar et al. 1990) but they have
been based on anecdotal descriptions with no supponing evidençe. Mobius syndrome could
serve as a mode1 to evaluate the effects of congenital paraiysis of the facial musculature on
the facial skefeton.
The influence on facial growth and developrnent. with the additional involvement of cranial
nerve V. has not been reported and the amount of vertical growth of the face has not
previousl y been considered.
Finally. if the craniofacial skeletal morphology of individuals with Mobius syndrome is
significantly different than controls, future studies are indicated to detemine whether gracilis
muscle transfer results in changes in the craniofacial morphology.
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OBJECTIVES
The objectives of the study were:
1 . To determine the craniofacial skeletal rnorphology associated with Mobius syndrome. via
Iateral cephalometric analyses.
2. To describe the craniofacial skeletal morphology associated with Mobius syndrome
involving cranial nerve V. in addition to cranial nerve VU, via lateral cephalometric
analyses.
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HYPOTHESES
1. The craniofacial skeletal morphology of individuals with Mobius syndrome is
significantly different than normal controls.
2. The craniofacial skeletal morpholopy of individuals with Mobius syndrome is more
severely altered if cranial nerve V is also involved.
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M A T E W L S AND METHODS
Samplr
This study was cross-sectional and rerrospective. Thiny lateral cephalornetric radiographs of
individuals with Mobius syndrome were available for the study. Twenty-seven were obtained
from the Orthodontic and Plastic Surgery Depanments at The Hospital for Sick Children,
Toronto and 3 frorn the Orthodontic Depanment at the Montreal Children's Hospital.
Montreal. The diagnosis of blobius syndrome and cranial nerve involvernent were confirmed
through medical records. lnclusion criteria consisted of Caucasians with Mobius syndrome
wi th bilateral facial paral ysis who had cephalom etric radiographs taken prior to onhodontic
treatment. All had cranial nerve VI1 involvement while four had cranial nerve V involvement
as well (Table 13). The individuals with trigeminal nerve
separately as a subgroup for analysis. The primary samp
involvement were considered
le therefore consisted of 26
individuals with bilateral facial newe paralysis and the secondary sample consisted of 4
individuals with bilateral facial nerve and trigeminal nerve involvement. Details of age and
sex distribution are provided in Table 14.
Ten subjects had recently undergone gracilis muscle transfers by Dr. R.T. Manktelow and
Dr. R.M. Zuker at The Hospital for Sick Children. Toronto, Canada at or close to the time of
the lateral cephalometric radioyraphs but no later than 6 months (range: 3 days-6 months)
post-operatively to preciude any effects of the surgery on the skeletal morphology.
Control groups were randomly selected from a pool of 1632 normal individuals from the
Burlington Growth Center. University of Toronto. Canada. The primary and secondary
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sarnple were matched for age. sex and race to 52 and 8 normal controls respectively (Table
14).
hk thocko/om
Lateral cephalometric radiographs, taken in occlusion. were used in the analysis. The
cephalometric radiographs of the sample were taken at the Hospital for Sick Children and
The Montreal's Children's Hospital. The cephalornetric radiographs of the control yroup
were taken from the Burlington Growth Study The enlargement factor at the rnidsasittal
plane was similar for al1 three cephalornetric units. Skeletal landmarks on ali lateral
cephalometric radiographs were identified. traced and dijitized using the Dentofacial Planner
7.0 software. Inter-examiner reliability of the traced cephaloyrams and the corresponding
landmark identification was performed in the Onhodontic Departrnent at The Hospital for
Sick Children. Intra-examiner reliability for digitization was also confinned through
intraclass correlation. .A total of 20 landmarks were identified (Figure 7) from which 30
angular, linear and proportional values were obtainrd (Figure 8 a. b. c). A description of the
cephalornetric measurements is located in Appendix A. The measured values are located in
Appendices B. C, D. E and the cephalornetric tracings are located in Appendices F and G.
The statistical analysis was performed in the Research Institute at the Hospital for Sick
Children using the MiniTab 12.0 Statistical Analysis Package and SAS 6.12. Repeated
measures analysis of variance for factors of age (0 - 1 1 .1 1 years, 12 years - 14.1 1 years, IS
years - 2 l years). sex (male and fernale). and group (Mobius and Control) were conducted. A
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preliminary analysis of the data using Manova revealed no overall agdsex, sedgroup or
agelgroup di fferences therefore the sample was col lapsed into 2 groups. Subsequentl y a
Univariate Anova was perfomed on each individual measurement. A significance level of
p= 0.05 was applied to al1 analyses.
The prirnary sample of individuals with Mobius syndrome was assessed separately from the
secondary sample. Complete statistical analysis on the secondary sample yroup was not
performed due to the small sample size. but means and standard deviations were used to
describe aiid to compare the rneasured variables to their respective matched controls.
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Table 13: Mobius sample listing gender, age. cranial nerve VI1 involvement *, cranial nerve V involvement *. and time of lateral cephalogram.
Sample Cender Age C.N. VI1 C.N. V Time o f Lateral Cephalogram
J.B. b1 4. X * prc-trcritmcnt P . F 5.6 * prc-treritmcnt K.M. F 6.4 * 5 rno post-op grricilis transfer M.R. F 7. J * pre-treatmen t D.D. M 7.4 * pre-treatment B.M. .M 8.0 * * prc-trecitment
T.G. F 8.4 * pre-treatmcnt E.S. kf 9.6 t prc-treritnicnt K . . F 9.1 l 1; 4 rno post-op gnciiis t m s k r T.W. F 10.6 t pre-treatmcnt C.G. F 1 1 . 1 1 * prc-treatment B.V. F t 2.0 * 3 rno post-op gncilis t m s f c r T.H. F 12.2 * pre-treatment L. P . kt 12.7 t prc-trcatmcnt R.C. ,CI 13.1 * 3 d a 3 post-op gracilis tr:msfcr R.K. ,LI 14.1 t pre-treritrncnt R.S. bl 14.3 1i: 4 mo post-op gncilis transfer W.M. ,LI 14.1 1 * * pre-treatmcnt P.R. hl 15.3 * 4 mo post-op gncilis transtkr A D .LI 15.3 t prç-trccitmsnt T.bI. ,LI 15.0 * J mo post-op gncilis transfer X.H. F 15.10 * 5 mo post-op gncilis transfcr J.D. F 16.6 * prc-trcritrncnt C M . kt 15.9 * prc-trcatment B.H. F 16.2 * 6 mo post-op gncilis t m s f e r K.H. F 16.3 * J mo post-op gncilis transfer H.M. F 16.7 * * pre-treatment
J.B. M 16. I l t * pre-treatment
C. S. .hl 17.1 * pre-treritment S.M. F 20.6 * pre-treatment
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Table 14 : Sample and control distribution
Primary Primary Secondary Secondary Sample Controls Sample Con trol
Total number 26 52 4 S Overnll mean [years) Overdl range (years) Number of males Male mean age (years) Male age range (years) Number of females Female mean age (years) Female age range (years)
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Ficure 7: Shelctal Ianilmürks on the Iütenil crpli;ilugram: S. sella. Fieurr Hu: Linru measurernenls on Iülrr~l sephrilogrnm: 1. S. nasion: .\. :\ point; B. F3 point; (in, gnlithiun; lie. nienton; ( i i i , I1;trvold m;isilIün lrngth (Co-Sn). 2 Flantild m~ndihii1;ir Iength gonion: .L. ~niciil;irr; Co. ~undvlilin; Ba. hasion; PSS. postcrior (Co-Ch). 3. fI;in.olJ nisxillün-mandihular unit lcngth ditkence. nasal .ipinc: :\>S. anterior nwd ïpinr: Sn. whnasüle; Sn' 4 Ba-PSS. 5 . PSS-.A point. o . C'o-Cio. 7. Gu-Cin. 8. Sri-Xlc. 9 .iuhnasdr'. ('IX uppcr incisor ~ p t s ; LIE. uppcr incisur dp: { ' F N IO. 1-FH. I l . [ ' t !O NF. 12. LI to JtP. 1.3. t ) v e r j e ~ 14. LI.4. loner incisot ripes: LIE. lowct inciser edgc: t'ti. uppcr tint iwrbitc. 15. I 'ci to SF. 16. 1-6 to )!P. 17. Ba-S;i molar edge: L6 I w r r tim molar dgr .
Figure Nb: . h g u l u mrrisurements on Ititenl crphülugmm: 1. SNA. 2. SNB. 3. ;\NB. 4. Ba-S-Sa. 5. gonial angle. 6. interincisa1 mgle. 7. 1'1 to NF. 8. LI to MP. 9. Ba-Sa-Co-(in. 10. Bo-Nd-.-\ point
Flrure Ilc: Roponiond measurrmcnrs on laiitnl cephalogram: C T H : LRI. L1 -me: Nri-mc
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RESULTS
The intraclass correlation showed excellent digitization reliability (ICC > 0.99). thus there
was no significant intra-examiner error (Landis & Koch 1977). blultivariate tests of
agelsedgroup and their 3 way interaction showed significance of the main effects only. The
p-value for age, sex and yroup were 0.000 1 . 0.0007. and 0.0002 respectively. The interaction
p-values were 0.56 for ageisex. 0.47 for ayeigroup and 0.46 for sedgroup. The results of the
Univariate Anova for the skeletal landmarks of the primary sample (n=26) and control group
(n=52), aiong with the means and p-vaiues. are surnrnarized in Table 15. The means and
standard deviations for the skeletal landmarks for the secondary sample (n=4) and control
group (n=8) are presented in Table 16. The statistical data is located in Appendix H.
The laterai cephalometric analysis showed significant differences (p < 0.05) for I O of the 30
measured variables for the primary Mobius sample. The cranial base lengh (Ba-Na) was
significantly shoner (p <0.O 1 ) while the craniai base angle (Ba-S-Na) was not signitïcantly
different. In the anteroposterior dimension. the ANB angle was signiticantl y larger (p< 0.05).
The Harvold maxillary length to mandibular unit length difference was significantly smaller
(p< 0.05) but no siynificant difference was observed with SNA, S N B and Ba-Na-A point.
The Harvold mandibular length (Co-Gn) and the lower border of the mandible (Go-Gn) were
significantly smaller (p < 0.01) while the posterior border of the mandible (Co-Go) and the
gonial angle were not signi ficantl y di fferent. The Harvold maxi1 lary length (Co-Sn), Ba- A
point and pharyngeal space (Ba-PNS) were significantly srnaller (p < 0.05. p < 0.01, p < 0.01
respectively) but PNS-A point was not significantly different. With respect to the vertical
dimension, the upper face height (WH) was significantly shoner (p < 0.05) while the total
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face height (Na-Me). lower face height (LFH). upper to lower face height ratio (UFH:LFH),
and the angle between the cranial base and the mandible (Ba-Na-Co-Gn) were not
signi ficantly different. No signi ficant differences were noted in the angular and l inear
measurements of the maxillary and mandibular incisors and first molars (U1 to NF
degreeslmm, L1 to MP degreesimm. overjet. overbite, interincisal angle. U6 to NF. L6 to
MP).
Due to the small sample size. statistical analyses were not performed on the secondary
sample, but several findings were noted. The cranial base length (Ba-Na) was also shorter. In
the anteroposterior dimension. no difference was noted in the ANB angle as compared to the
primary sample versus control. The Harvold mandibular length (Co-Gn). posterior border of
the mandible (Co-Go) and gonial angle were larger than the measured controls. The Harvold
rnaxillary length (Co-Sn). Ba-A point. PNS-A point and pharyngeal space (Ba-PNS) were
smaller and the Harvold maxillary length to mandibular length difference was larser.
Measurement in the vertical dimension ( Na-Me. WH. LFH. üFH: LFH, and Ba-Na-Co-Gn)
al1 indicated a more vertical pattern of growth. Measurements describing the angular and
vertical position of the maxillary and mandibular incisors and first molars (U1 to NF
degreedmm. L 1 to MP degrees/mm. U6 to NF, L6 to MP) indicated that the maxillary and
mandibular incisors were overempted but the rnaxillary and rnandibular first molars were
even more overerupted. This was also confirmed by the lack of overbite.
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iii
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DISCUSSION
There are approxirnately 200 cases of Mobius syndrome reponed in the literature
(iMacDerrnot et al. 1990) but there have been no studies to determine the craniofacial
skeletal morpholoyy . Abnormalities such as micrognathia and midface prominence have
been claimed as features of Mobius syndrome. but they have been based on anecdotal
descriptions with no supporthg evidence.
Microgathia has been the most frequently mentioned craniofacial skeletal abnormality in
the literature (Table 10). Except for the 3 cases reported by Bnggs (1965), Gutman et al.
(1973) and Rizos et al. ( 1998). reports of associated craniofacial findings have been based
on clinical examinations rather than standardized cephalometric studies. The incidence of
micrognathia associated with Mobius syndrome may have been overestimated in the
literamre due to the use of soft tissue assessments with the iack of distinction between a
reduced size and reduced or rotated position of the mandible and its position relative to the
maxilia. Clinical assessments of the soft tissue do not accurately differentiate these
di fferences.
Micrognathia is a reduced size of the jaw whereas retrognathia irnplies a retruded position.
The size and position of the mandible is more accurately assessed on a lateral cephalometric
radiograph where it is possible to assess whether the mandible, in profile. is 1 ) micrognathic
relative to the other structures of the craniofacial cornplex, 2) normal size and position but
retognathic relative to a prognathic or normal maxilla, and (3) normal sized but wiih a
clockwise rotation, thus functioning in a retrognathic position relative to a normal maxilla.
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Althcugh the use of lateral cephalometric radiographs to determine the skeletal craniofacial
morphology is more accurate than soft tissue assessments. there is an inherent danger in
using linear measurements when comparing an affected group of individuals to a non-
affected control group. The affected group may be larger or smaller individuals in al1
dimensions than the controls, and thus incorrect conclusions can be drawn from the
measurements. If the individuals with Mobius syndrome in this sample are smaller overall as
a group than the Burlington control group. then measurements which are proportionately the
same will appear to be srnaller. and may even have statistical significance. There are two
ways to overcome this problern: either use angular and proponionai measurements, or size-
adjust the samples One method of accomplishing the latter is to accept the cranial base
length (Na-Ba) as a standard length in the skull that is not affected by the anomaly being
studied. This rnethod is accurate in studies involvin_r individuals with a cleft lip and palate,
where the cranial base is not affected by the presence of the cleft (Ross 1987). The mean
cranial base lensth (Na-Ba) of the Mobius group is smaller. and it would appear justifiable to
size adjust al1 skeletal linear measurements to reflect this. If this was done as in colurnn 7 of
Table 15. many of the differences between the samples disappear. There is no proof,
however, that size-adjusting For these individuals is valid. Although it seems a sensible
method to improve the accuracy of these results. it can only be considered a hypothetical
improvement.
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Primary Samole - Craniofacial Findines
The results from the lateral cephalometric analysis for the primary sample showed significant
differences (p <0.05) for I O of the 30 measured variables. Eight of the 10 measured variables
were linear. one was angular and one was proportional. Although not proven statistically.
size-adjustment of the linear measurernents accordin3 to the cranial base length (Na-Ba)
suggests that individuals with Mobius syndrome have a smaller craniofacial corn plex overall
and that the anteroposterior positions of the maxilia and rnandible are proportionately sized
to the craniofacial size (Table 15).
Without size-adjustments, the results of this study indicate that the Harvold mandibular
length (Co-Gn) and the size of the lower border of the mandible (Go-Gn) were significantly
smaller (p ~ 0 . 0 1 ) ihan the control group but the length of the posterior border of the
mandible (Co-Go) was not significantly differenr. The results also indicate that the Harvold
maxillary length (Co-Sn) was significantly smaller ( p <0.05) than the controls but not PNS-
A point. The Harvold mavillary length to mandibular unit length difference was si~nificantly
smaller (p <0.05) by 2.5 mm.
It should be noted that the rneasured values for the Harvold mavillary length, Harvold
mandibular length and Harvold maxillary io mandibular unit length difference for the
primary sample are comparable to the Harvold mean values (Harvold 1974) and even more
so when these values are size-adjusted (Table 17). Therefore. the mandible should not be
considered rnicrognathic or abnormaily small based on these measurements (Figure 9 a, b).
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The anteroposterior position of A point and B point (SNA, Ba-Na-A point and SM3) were
sirnilar to the controls indicating a similar anteroposterior position of the maxilla and
mandible relative to the cranial base. Therefore, the previous suggestions of a rnidface
prominence (Henderson 1939, Gorlin et al. 1990) could be attributed to erroneous clinical
observations or to soft tissue characteristics. The on1 y significantly different angular
measurement was ANB ( p < 0.05) but a siynificantlv larger ANB angle does not imply a
micrognathic mandible but rather indicates a relative spatial difference between A point, Na,
and B point.
Tiihle 17: Hmold mcms (H'wold 1974). control group nieans. priniiq sample mcms and size-adjusted means for Hmold niiisillary length. Hmold rnandibiilar length and HmoId rnrisillary to mandibulw unit length difference
Croup Gender Age Hun.c)ld muxilliiry Humold mrindihular Hünfold muxillury tci SUF [yeurs) Icngth (Co-Sn) length (Ci)-Gn) mandihular unit
length diffwcncc Harwld Meun ,CI t 2 LI? inm 2 3.73 I l 4 mm 24.9 72 nlin
F 12 mm 2 4.07 Il.? nim 25.2 23 mm Contrd Croup hl / F' 12.4 li 1 .h mm 2 7 .2 I 1J.H mni I l0.I 24.0 mm + 4.7 Primury Sample M / F If.? W.4 mm i 7.4 1 Iii.2 mm I I 1 . R 21.3 mm f 7.2 Size-Adiurted fibr Nu-Bu M f F 1 . 3 92.4 nim 1 1-3.9 mm 72.2 mm
Except for a significantly shorter (p <0.05) upper face height (UFH), no significant
difference was noted with respect to vertical face height. Again, size-adjustment resuits in
comparable values for this variable (Table 15).
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Figure 9a: Harvold m a u i l l w length (Co-Sn) of prirnanl sample and control group
60 ------- . -.-- ---- ---- -- . .----
4 b X 10 12 I - l Ici 1 S ?O 12
Figure 9b: Harcold mandibulx Icngth (Co-Gn) of primary sanipk and control group
H a n o l J i+lundihul:ir Length (Co-Gn)
, Primury .\lubius Sumple ,
, Control Gmun
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Primary S a m ~ l e - Dents1 Findines
The findings of this study indicated that the maxillary incisors were not protrusive as
reported by Federman and Stoopack (1975). Although not statistically significant, the
angular positions of the mavillary and mandibular incisors (U1 to M. L I to MP and
interincisal angle) suggested a more upright positioning. Paralysis of the muscles of facial
expression may in Fact cause a constant direct force on the maxillary and mandibular incisors
similar to orthodontic forces and thus could result in a more upriyht positioning of the
anterior teeth.
An anterior open bite was reponed by Rizos et al. (1998). but the amount of overbiie
observed in the study was identical to the normal controls and the maxillary and mandibular
incisors and first molars were not over or underenipted.
S i ~ r ~ ~ r n m - t , of Pritmrv Jilri~pie
In summary, this lateral cephalornetric study showed that the craniofacial morphology
associated with Mobius syndrome was significantly different (p ~ 0 . 0 5 ) than the control
group for 10 of the 30 measured variables. However, this study sugyested that individuais
with Evlobius syndrome may have a smailer craniofacial complex given the significantly
smaller cranial base length (Na-Ba). Without sire-adjustment, this study suggested the
presence of a smaller maxillary and mandibular length (Co-Sn, Co-Gn) but the measured
values fell within the range of the normal Harvold means and standard deviations (Table 17).
Also, the anteroposterior position of the maxilla and mandible was simiiar to normal
controls. Using only angular measurements, it appean there are no real differences between
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the two groups and there is no evidence to suppon the inclusion of rnicrognathia and midface
prominence as çkeletal craniofacial features associated with Mobius syndrome. The overall
findings can be observed on the mean facial diayrams of the primary sample superimposed
on the control group. (Figure 10 a. b. c).
Secondarv Sample
Due to the srnall sample size of the secondary sample with trigeminal nerve involvement
(muscles of mastication), statistical analysis was not possible. Individuals with Mobius
syndrome in the secondary sample can be described as having a craniofacial morphology
which was extreme with respect to the vertical pattern of growth, amount of clockwise
rotation of the mandible and anterior openbite.
The lack of functioning muscles of mastication and the effects on the craniofacial
morphology may be comparable to that seen in congenital muscular dystrophy. myotonic
dystroph y, Duchenne muscular dystrophy and Facioscapulohumeral muscular dystrophv
where an extreme vertical pattern of growth and anterior openbites have also been observed
and have been attributed to the lack of functioning of the muscles of mastication (Hanson et
al. 1971, Kreiborg et al. 1978, Kiliaridis et ai. 1989. Eckardt & Harzer 1996). These findings
suggest that the lack of function of the muscles of mastication is more likely to affect the
craniofacial skeletal rnorphology than the lack of function of the muscles of facial
expression. It should be kept in mind that the paralysis of the facial and rnasticatory
musculature is progressive in these conditions whereas the paralysis is non-progressive in
Mobius syndrome.
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Unlike the primary sample. a substantially larger difference was observed between the
Harvold rna~illary and mandibular unit length difference. This could be attributed to both the
srnalier maxillary length or the larger mandibular lensth observed. The mandibular length
was very large as compared to the control group and the primary sample. Class I I I
malocclusions have been previously reponed by Thomas 1898. Briggs 1965. and Chester &
Zuker 1992. but the extent of the trigeminal nerve involvement was not reported. Unlike the
primary sample, whose mean overbite was identical to the normal controls. the secondary
sample exhibited large openbites similar to Rizos et al.'s (1998) case report.
Smmarv o f S t ? ~ ~ o ~ ' m + y hhmple
The secondary group had a more extreme pattern of vertical growth of the face, a retmded
mauilla. larger mandibular lengths and anterior openbites (Figure 1 1. 12). Further controlled
studies with a larger sample size are indicated in order to determine the significant difference
between individuals with Mobius syndrome with and with out trigeminal nerve involvement.
Obtaining an adequate sample size may be difficult given thal trigeminal nerve involvement
occurs in approximately 6%- 8% of individuals with Mobius syndrome (Engler et al. 1979.
Carr et al. 1997). The overall findings can be observed on the mean facial diagrams of the
secondary sample superimposed on the control group (Figure 13 a. b. c).
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Figure 10a: Mean latenl ccphalometric tracings: p r i m w sample supcrimposed on control group at Ba-Na.
Control group Primav saniple (C.N. VI1)-------
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Figure lob: Mean lateral cephalometric tncings: pnm- sample superimposed on control group at ANS-PNS.
Convol group Prima- samp le (C. N. VI 1 )----------------
Figure ~ O C : blran Iritcnl ccphalomrtric tncings; prim- samplr: superimposrd on control group on mandibular plane.
Conuol group Prin i rc sriniplc (C. N. VI1 1--------------
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Figure I l : Lateral cephalometric radiographs- priman, sarnple.
Figure 12: Laterd cephalometric radiographs- second- sampie demonstrating vertical pattern of growh. Iarge mmdibular length and antcrior opeubite.
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Figure 13a: Mean lateral cephalomçtric tracings: seconduy sample superirnposcd on control group at Ba-Na.
Controi group Seconda? sarnpk ( C . N V)---------
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Figure 13b: Mean latcnl cephalornetnc tncings: second.. sample superimposed on control group at ANS-PNS.
Conrrol group Sccondan srtniplc (C. N. V)------
Figure 13c: Mcm latrnl ccphaiomctric tncings: second-. smple stipenmposcd on control group on mandibulx plme.
ConuoI g o u p Sccondan srmipic (C. N. V)------------
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CONCLUSIONS
The purpose of the study was to determine the craniofacial skeletal rnorpholo~y associated
with Mobius syndrome. Anecdotal descriptions of the soft tissue of the face and three case
reports which included lateral cephalometric findings have been reported in the literature. but
cephalometric studies looking at the craniofacial skeletal morphology are absent. The present
study is the only one which has used cephalometric radiographs to objectively examine the
craniofacial morphology associated with ;\lob ius syndrome versus normal controls. The
finding of this study indicated the following:
I The craniofacial skeletal morphology associated with Mdbius syndrome. without trigeminal
nerve involvement. was significantly different (p< 0.05) for 10 of the 30 measured variables.
However. individuais with Mobius syndrome may have a smaller craniofacial complex given
the significantly smaller (p ~ 0 . 0 1 ) cranial base lenpth (Na-Ba). When the 8 linear
measurements were size adjusted to the cranial base length. the Mobius group was
comparable to the control group. Even without size adjustment. the size of the maxilia and
mandible were within the range of normal Harvold mean values. Thus, this study refutes the
daims of a midface prominence and a rnicrognathic mandible being associated with Mobius
syndrome and indicates that. except for overall size of the craniofacial complex, there is little
di fference in the s keletal cranio hciai rnorp hology.
2. The small sample of individuals with Mobius syndrome, with trigeminal nerve involvement,
had an extreme pattern of vertical growth with clockwise rotation of the mandible, an
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anterior openbite and overeruption of the rnaxillary and rnandibular molars. A smaller
rnaxillary length with a laqer mandibular length was also observed.
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FURTHER RESEARCH
Reanimation surgery is ideally performed at an earlier age for psychosocial and speech
concems. Whether gracilis muscle transfer resul ts in a more favorable pattern of facial
growth and development has not been established. This study suggests that the craniofacial
cornplex is less affected when the trigeminal nerve, and hence the muscles of mastication,
are not involved. Early surgical intervention may be more critical with those individuals with
trigem inal nerve invo lvement where the cran io facial skeletal morphology seems to be more
severeiy altered. Longitudinal studies. to determine the long-term facial growth and
development of individuals with Mdbius svndrome who have undergone gracilis muscle
transfer at various ages. are currently undenvay at The Hospital for Sick Children.
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Kreiborg B. Jensen B.L. Moller E, Bjork A.: Craniofacial growth in a case of congenital muscular dystrophy. A roentgencephalometric and electromyographic investigation. Am J Orthod. 74; 2; 207-2 15: 1978
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Landis J.R Koch G.C.: The measurement of observer agreement for categorical data. Biometrics. 33; 1 59- 174: t 977
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Mobius von P.J.: Ueber angeborene doppelseitige abducens-facialis-lahmuny. Munchener Medicinische Wocherischrifi. 6 . 9 1-94: 1888
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Riggs E.H. : Congenital hypoplasia of the facia. Ibid. 1 7; 520: 1958
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Rubin L.R.: The Mobius syndrome: Bilateral facial diplegia. A course on the symptorns. pathology. and a surgical dynamic animation of the paralyzed face. Clinics in Plastic Surgery. 3; 4: 625-636. 1976
Rubin L.R, Lee G.W, Simpson R.L.: Reanirnation of the longstanding partial facial paralysis. Piast Reconstr Surg 77; 1 ; 4 149: 1986
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Slee J.J. Srnan R.D. Viljoen D.L.: Deletion of chromosome 13 in Moebius syndrome. J Med Genet. 28; Ji 3 - 4 4 199 1
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Spatz H, Ullrich O.: Klinischer und ana Beitras zu den angeborenen Beweglichkeitsdefen Himnervvenbereich. Z Kinderheilk. 5 1 ; 579-597: 193 1
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Stabile M, Cavaliere M L , Scarano G, Fels A, Valiani R, Venturo V.: Abnormal B.A.E.P. in a family with Moebius syndrome: evidence for supranuclear lesion. Clinical Genetics. 25; (159-463 : 1984
Stansbury J.R.: Moebius syndrome. Congenital oculofacial paralysis. A case report. Am J Ophthalrnol. 35; 265-26 1 : 1952 Steiner C.C.: Cephalometrics for you and me. Am .i Ortho. 39; 10; 729-755: 1953
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Sugannan G. 1. Stark H.H.: Mobius syndrome with Poland's anornaly. J Med Genet. 10; 192- 196: 1973
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Van Allen M. W. Blodi F.C.: Neurolopic aspects of Mobius syndrome. Neorology. 10; 249- 259: 1960
Van Buskirk C. : Consenital facial diplegia. US Armed Forces bled 1. 2; 1553: 195 1
Van der Weil H.I.: Hereditary congenital facial paralysis. Acta Genet Statist Med.7; 348: 1957
Von Graefe A. Saernisch T. eds. Handbuch der gerammten Augenheilkunde. Vol 6 Leipzig: W Engelmann: 1880
Von Zirnmerman W.: Beitrag zur Kasuistik angeboren doppelseitiger fazialis Lahrnngen.2 Laryng Rhinol Otl. 45; 676-65 1 : 1966
Wallis P.G.: Creatinuria in Mobius' syndrome. Arch Childh 35; 393-395: 1960
Wedgvood D.L. . Moebius syndrome J Can Dent Assoc. 9: 4 17-120: 1975
Wilson-Pauwels L, Akesson E.J. Stewart P A . : Cranial nerves. Anatomy and clinical cornments B.C.Decker Inc Ontario. 1988
Woodside D.G.: Cephaiometric Roenteeno~ra~hv. Harper and Row Publishers Inc. Hagerstown Maryland. 5-28: 1976
Yasuna .J, Schlzinger N. : Congenital bi lateral abducens: facial paralysis (Mobius syndrome). Arch Ophthalrnol.54; 137- 139: 1955
Ziter F A , Wiser W.C. Robinson A.: Three-generation pedigree of a Mobius syndrome variant with chromosome translocation. Arch NeuroI. 34: 437-442: 1977
Zuker R.M. Manktelow R.T.: A srnile for the Mobius syndrome patient. Ann Plast Surg. 22; 188- 194: 1989
Zuker R.M.: Facial paralysis in children. Clinics in Plastic Surgery. 17; 1; 95-99: 1990
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Operational Definitions
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Operational Definitions
Cephalometric iMeasurements
Sella Nasion to Point A (SN;\): thc anglc cstriblishcd b'. the lincs connccting thc thrcc points. Sclla Tursica Nasion and Point A
Sella Nasion to Point B (SNB): the anglc cstablished by the lines connecting the thrce points. Sclla Tursica Nasion and Point B
Point A to Point B difference (ANB): thc anglc cstablishcd by the lincs connçcting the thrcc points. Point A. Nasion and Point B
Basion Nasion ta Point .A (Ba-Na-A point): thc anglc cstablished b!* the lines connecting the thrcî points. Basion. Nasion and Point A
Maxillary Length (Max length): the distmcç in mm from the rnost posterior-supcrior point on the hcad of the condyle (Co) to Subnaale
blandibular Length (%land length): the distancc in mm frorn the most posterior-superior point on the hccid of tlic coiid!ltt (Co) to Cinathion
Unit length Differences (Max-Mand diff): martdibular unit lrngth minus rnaxillary unit length
Basion to Posterior llasal Spine (Ba-PNS): the distance in mm from Biision to Postcnor Nasal Spinc
Posterior Nasal Spine to Point A (PNS-A point): the distaiicc in mm from thc Posterior Nasal Spinc to Point A
Basion to Point A (Ba-A point): thc distai~cc in mm from Basion to Point .A
1 1 . Condylion to Gonion (Co-Go): thc distance in mm from the most posterior-superior point on the head of the condyle (Co) to the angle of the mmdiblc
17. Conion to Gnathion (Co-Gn): the distance in mm from the angle of the rnandibls to the most inferior and mterior point on the chin (Gn)
13. Conial angle: the angle cstablished by the lines connecting the three points Condylion. Gonion. and Gnathion
14. Nasion to Menton (Na-Me): the distance in mm from Nasion to Menton
15. Upper Face Height (UFH): the distance in mm fiom Nasion to Subnzale*
16. Lower Anterior Face Height (LFH): the distance in mm from Subnasale' to Menton
17. Face Height Ratio (FHR): the ntio dçtermined by the equation URVLFH
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18. Basion Nasion to Condylion Gnathion (Ba-Na to Co-Gn): the angle establishcd by the lines Basion to Nasion. and Condylion to Gnathion
19. Upper Incisor to Nasal Floor (U1 to NF): the posterior-superior anglc formed by thc intenection of the lines dnwn through thc long avis of the most prominent niauillary incisor to the line n-hich conncct ANS to PNS
20. Upper lncisor to Nasal Floor, height (U1 to NF): the mm distance drawn bctwen the tip of the ixisal edge of the most prominent r n u i l l q 8 incisor perpendicular to the line which connects ANS to PNS
21. Lower lncisor to Mandibular Plane (dl ( L l to MP): the postcrior-superior angle formed b!. the intersection of the lines d m v n through the long %vis of thc most prominent rnuidibulor incisor to thc mandibular plant:
22. Lower lncisor to ~Mantiibular Plane, height ( L l to MP): the mm distance d r w n bctnwn the tip of the incisai edge of the most prominent mandibular incisor pcrpcndiculrir to the mandibulx plant:
23. Lower incisor and Menton to Nasion and Menton Ratio (Li Me: Na Me): thc ratio dcttlnnined by the equation L 1 -Me/Na-Mc
24. Interincisal angle: the angle formed by the intenection of the lines dnwn through the long mis of the rna~illary and mandibular centrai incisors
25. Overjet: th6 horizontai distance in nim from dic incisd edgc of thc most prominent m a ~ i l l q incisor to the incisril cdge ofthe most prominent mmdibular incisor
26. Overbite: thc venicd distuicc in mm from the incisd edge of the most prominent n~a..illary incisor to the incisa1 edge of the most prominent mandibulm incisor
27. Upper Molar to Nasal Floor, height (U6 to NF): the mm distance drawn betwcen the tip of the incisal cdge of the mwill- fint rnolar psrprndicular to the line which connects ANS to PNS
28. Lower Molar to iMandibular Plane, height (L6 to IMP): the mm distance drawn behvecn the tip of the incisal rdge of the mandibular first molsr perpendicular to the mmdibular plane
29. Basion to Nasion (Ba-Na): the distancc in mm from Basion to Nasion
30. Basion to Sella to Nasion (Ba-SNI): the mgle rstablished by the lines connecting the three points. Basion. Sella and Nasion
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APPENDIX B
Raw Data: Primary Sample
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---- -- y]. 1 7 t =r\ -3. t. F ~ F ~ . iq~m sl - 3 7 3 =\ in ~n e t x. ln I? C I C = fi r- + pi fi 3 r- a =c F. w, * lh th & w 1 - ~ x + & I ~ , s FI + , - p # + C I - I A ; C - E r ? r - ~ ~ c f . ~ t 5 m C I X 3 # m e c r i - c.I
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_ *- -.- - ..-_ .-_- _-.-.-. - - . .-* ---. *__IC ------- ~ ~ ~ 3 ~ 3 . 3 , 3 , x ~ . = , ~ X . ~ - 3 - c . N . ~ 3 . - , m X \ = N ; . 3 =\ = - $ = i n r-- 45 =.\ \1 = -r 3 f \ = X & yz p J ' - , - & 6 pli ?\ + e l e - N r r ~ x i C , ~ 2 = m
c. r - 2 = ? m . = P I
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Raw Data: Secondary Sample
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Raw Data: Control for Primary Sample
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1 , 8
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I l t j : ! . , : ! ! : . I b < - 0 1 ' 1 ! ! - , j j - o n j v l m t v i ~ i - ~ , ~ l ~ , ~ ~ ~ t ~ , t n ~ ~ m m m a i a ~ m l m , r n 4 s 3 ~ i m ri a l ~ i & ~ i i i i i i ~ l a ~ N I - ! ~ , , U ! D I - ! n i n T 1 + ! n / r n l ~ I ~ i - i q , a , , - , - I ; c ~ ~ ~ = j c ( o , n 1 n y n i m I n m - , - I :
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APPENDIX E
Raw Data: Control for Secondary Sample
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c l -
1 , : l :
I I ,
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Cephalometric Tracings: Prirnary Sample
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j * b . (M)
d . d . (H)
e . s . (U)
m . r . (F)
k. j . (F) t. W. (F)
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b . v . (F) t * h . (F)
r. c . (n) r . k. (H)
r. S . (H) a . d . (H)
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j . d. (F) c . m. (M)
a. h. (F) b. h. (F) k . h. (F)
S . III. (F)
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Cephalometric Tracings: Secondary Sample
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b . m. (M) 8y Om
h . m . (F) 16y 7m
W . m. (H) 14y I 1 m
j . b . (H) 16y I l m
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APPENDIX H
Statistical Data
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n1mr wmrr re l l aa l l i t y :
r r l l ~ O ~ 1 1 r v : u & n QI -WU€- SI 168 wf EMS EW EUS üW $(d JDF K hifT* s inglr scorr k scores
w - wr use n*5 EMS r w sra
XOllf 0.14545 34S.375 0. l4S45 O.Il345 10 345.175
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S t a t l S t i C V a lue C Hum Of Oen OF P r F
w i l k s ' Cauwia 0.31614373 0.9602 60 74 0.5620 P i l l a i ' s Trace 0.67497443 0,9851 60 76 0.5205 n o t e l l i q - l a i l e y Trace 1 .5585(U195 0.9352 60 72 0.6035 Roy's Gre l tes t R w t 0.83r93049 1.0531) 30 33 0.4348
Manava Test C r l t e r l a and F Aqproximations f o r t n t nypotnesis o t na O v e r a l l FSiEWGROUP E l l c c t tl - Type III SS4CP U a t r i r f o r AGE'CRUJP E = E r r o r SSdCP Matr i x
V i l k s ' L a r W I 0.29976801 1.0193 60 74 0.4657 P i l a i ' s Trace 0,18S23211 i.oaS9 60 76 0.4867 HoteLling-Lawiey Trace 1.7 la76866 1.0333 60 72 0.4476 Roy's Gfeatest Roat 1.20780521 1 -5299 30 38 0.1073
Manova Test C r i t e r i a ancl Exact F S t a t i ~ t l c l f o r th. Hypothesis o t no O v e r i l i SUgGROUP E l l e e t n = T y p e I I I SSICP utri1 l o r SEX.GAOUP E = E r m r SSCP U a t r f x
s t a t u t i c value F N u i OC Dan OF Pr * F
N i l k a ' U- 0.54432318 1.032s M 37 0 .498 P i l l a i ' s Tncr O -45567W 1. Ws 30 37 0 . 4 ~ Hot r l l i ng -LawleyTrace 0.û3714389 t.0325 30 37 0.4588 Roy's C n a t i s t R o o t 0.ô3714309 1.0325 30 37 0.4508
uanova Test t r i t e r l a and F Approxiriatiocis f o r the Hypotnasis or no O v e r a l l SE Er tec t H = Type III SSKCP Y l t r l x f o r AGE E = E r r o r SSaCP Y I t r i x
S t a t i s t i c Value F W D F DcnW P r . F
Wi lk r ' C a i W i 0.07227800 5.3542 60 74 0.0001. P i l l a i ' s Trace 1 .35424065 2 .ô564 60 76 0.0001 ~ o t e l i i n g - L n l e y T n c c 6.93428416 4.1606 60 72 0.0001 uoybs Gr ta tes t uoot s . s 4 i o ~ r i s 7 . 5 2 s 30 3a 0 ~ 1
UanoVa Test C r l t e r i a and Exact F S t a t i s t i c s f o r tri. t t ypo tn ts is o f no Overa l l SEX E f f e c t N - Type 1x1 SSaCP U a t r i x f o r SU E - Error SSICP U a t r i x
Sta t l s t i c V a l w F N u i O f Oen OF P r f
WiLks' L a M a 0.28711867 1.0622 30 37 0.0007 P i l l a i ' s Tnce 0.71289133 3.0622 30 37 O.Oû07 & t e l L i n g - L a r i e y t r a c e 2.482WM2 3.0622 30 37 O-aOO7 Roy's t r i a t e s t Raat 2.482ô8042 3 -0622 30 37 0.0007
Manova Test C r i t e r r a ana Exact F S t a t f s t i c s f o r t t m n y p i t l u s i s o f no Overa l l QlW E r f e c t M = Type III SSICP Y i t r i x f o r GROUP E = E r r o r SSLCP Y a t r i x
r i u s * u a d a 0.~59026s1 3.5281 3(] 37 0 . ~ ~ 2 P i l l a i ' s T n c e 0~74091349 3.5201 30 37 0.0002 m t e l l i n g - L a w l e y T n c r 2.56060976 3.5281 M 37 o.am2 Roy's Grra tes t Root 2.86060876 3.5211 30 37 0.0002
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C.V.
¶y# I I I Sf
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OF sui o r =u&rrr w r n Square F v a l u e P r F
Error 66 182.95154533 i3.37M15629
Corrrctra t o t a l I 7 i021.628333;2
Crror 66
W l n Square
Source D Su o f Squares man Squarr F Valu. P r F
91. 1-27 8.28256930 o . a . m t
657.21017619 9.9973449
7 ~ 8 . 3 l W 6
C.V. R a a t USE B r u Mean
4 .-285 3,15558702 63.23461530
E r r o r 66
Corrrcrea t o t a l 77
Source a 1- t t i s
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Errar 66 1699.61016667 25.15166919
OF type I l l SS wrn Squrrr F V a l w Pr J f
(i.ntral Cirurr w r k s Proceaur i
Dr S u . o ï Squrris urrn Squrrt V a l w Pr b F
Sm a f Squirtr Win Square F Valui pr . f
C.V. b a t USE Win
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f r r o r 66 1046.07739286 15 ai996050
ucrn S e ~ r r + F vil-r P r . F
R-Squrrr C.V. A O û t USE uwan
tne S& Systrm 14:22 uonoay. &ri1 26, 1999 218
t r r o r 66
C.V. fbot rSL W W8n
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30M. I W 3 3 3
C.V.
Source Of
Errar 66
Correctba total 17
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S u of Sqrurtr w r n Square C V a l r I r a f
1107 .X32Si57 160.66SJ#771 10.03 0.aoo1
662.%04$230 10.03009716
1769.O.37l795
C.V. Amr USE Wn W i n
6.1 ts42 3.16~5353 51.30197436
L r r o r 66
Source Of
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w r n Square i vrluc P r rn f
33.3207703t 1.86 0.6612
lt.9l126245
Corrmct.0 Tota l 77 154d.671?9(l7
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C.V. aoor r 5 ~ U I 2ttfu u a n
s&lrcr
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Source OC
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Source 0Ç L m o ï Squares w r n Spurr. F V a t w P r r F
corrtctra T o t a l 71 i 410 .02615~5
Source
Corrrcrro focal 77
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