craniofacial and dental study
TRANSCRIPT
Craniofacial and Dental Study
of Mulibrey Nanism
SINIKKA MYLLARNIEMI, D. ODONT.,
KALEVI KOSKI, D. ODONT.,
JAAKKO PERHEENTUPA, M.D.Helsinki, Finland
Denial and craniofacial features of 17 children and young adults suffering from therecently discovered mulibrey nanism syndrome are described and discussed. The present datado not allow any definite craniofacial typification of the syndrome. However, severalfindings suggest that we may be dealing with persistence of infantile structural relation-ships in the craniofacial area.
Introduction
Mulibrey nanism is a recently described
syndrome of growth failure with prenatal on-
set (Perheentupa et al., 1970; Perheentupa et
al., 1973).. The name was coined from muscle,
liver, brain, and eye, the organs most conspic-
uously involved in the first cases observed. So
far, 27 cases from Finland, one of Egyptian
origin from Sweden (Thorén, 1973), two from
Canada, and two from the United States
(Cumming et al., 1976; Voorhess et al., 1976),
and one in a Gipsy from France (L. Catholi-
neau, personal communication) are known to
us. The condition is probably determined by
an autosomal recessive gene (Perheentupa et
al., 1973). It is characterized by a triangular
face, often hydrocephaloid skull, thin hypo-
tonic musculature, peculiar highpitched
voice, ocular fundi with yellowish dots and
pigment dispersion, and raised venous pres-
sure with enlarged liver. The latter features
are due to pericardial constriction, which
seems to be a constant component of the
condition, though highly variable in extent.
Some of those affected die in infancy, but
others reach adulthood without severe inca-
pacity. As the tissues involved seem to be
mainly of mesodermal origin, the basic defect
may be of a gene determining an enzyme or
structural protein which is particularly essen-
tial to mesodermal tissues.
Dr. Myllarniemi is Assistant Professor of Pedodonticsand Orthodontics, Institute of Dentistry, University ofHelsinki. Dr. Koski is Professor of Pedodontics and Or-thodontics, Institute of Dentistry, University of Turku,and Dr. Perheentupa is Associate Professor of Pediatrics,The Children's Hospital, University of Helsinki.
369
The range of adult height is estimated to
be from 136 to 161 cm for males and from
126 to 151 cm for females. Growth failure
seems to be of a rather unusual type for,
although the epiphyses appear normal, the
growth of the limbs is more affected than that
of the trunk. Craniofacial growth also seems
to be characteristically altered. The very typ-
ical craniofacial features have not yet been
described in detail, although some informa-
tion based on the manuscript of the present
report has appeared in a new textbook (Gorlin
et al., 1976). A biometric description of cran-
iofacial characteristics in mulibrey nanism is
the subject of this report.
Subject and methods
Seventeen persons with mulibrey nanism,
eight boys and nine girls aged 1.4 to 24.4
years, were examined. In addition to the clin-
ical dento-facial examination, we took dental
casts, X-ray orthopantomograms, and lateral
cephalograms for all save the youngest pa-
tient.
From the casts, the mesio-distal and labio-
lingual crown dimensions were measured with
a sliding calliper. Morphological characteris-
tics of the dentition and dental occlusion were
also recorded. Dental age, i.e., the stage of
tooth formation, was estimated from the or-
thopantomograms.
Lateral cephalograms were taken using a
cephalostat. The midsagittal plane distance
was a constant 150 cm, and the midsagittal
plane-film distance was 11 cm. Some difficul-
ties encountered when X-raying the youngest
370 _ Cleft Palate Journal, October 1978, Vol. 15 No. 4
children led us to reject five films, so that 11
films, representing five females and six males
aged 6.8 to 24.4 years, qualified for dimen-
sional analysis.
The following linear measurements (Figure
1) were taken from the X-ray cephalograms
with a sliding calliper, read to the nearest
mm.:
gl-op, glabella-opisthocranion, length of the cran-
ium,n-s, nasio-sella, length of anterior cranial base,
b-s, basion-sella, length of posterior cranial
base,o-b, opisthion-basion, length of foramen mag-
num,
o-n, opisthion-nasion,o-a, opisthion-acanthion,o-id, opisthion-infradentale.
._ n-sThe ratio -- was also calculated.
e
The following angular measurements were
made:
F/C, the angle formed by the foramen magnumand the clivus planes,
C/S, the angle formed by the clivus plane andthe planum sphenoideum,
nsb, the angle formed by the n-s and b-s lines,N/M, the angle formed by the nasal floor line and
the mandibular base plane,M/R, the angle formed by the mandibular base
plane and the tangent to the dorsal border
of the ascending ramus,N/U, the angle formed by the nasal floor line and
the axis of the upper incisor,
F/N, the angle formed by the plane of the fora-men magnum and the nasal floor line.
The angles were measured from the lines
representing the respective planes drawn on
transparent paper fixed on the film and read
to the nearest degree.
The choice of the measured dimensions was
determined by available control data on Fin-
nish children and young adults (vide infra).
Results
Information on the youngest children in-
dicated that eruption of the deciduous teeth
had taken place normally.
Dental age, estimated from tooth formation
in ten patients aged 4.5 to 12.8 years was, like
skeletal age (Perheentupa et al., 1973), well
within normal limits when compared to Fin-
nish norms (Haavikko, 1970). The 12.8-year-
old boy was an exception, with dental age
retarded by as much as 2.9 years. His skeletal
maturation was also retarded by 2.3 years.
Labio-lingual and mesio-distal tooth di-
mensions correspond closely to the Finnish
norms (Rantanen, 1964; Alvesalo, 1971).
Traits of dental occlusion are listed in Table
1. Dental arch crowding was a common fea-
ture of the permanent dentition. In several
cases, it had been treated with tooth extrac-
tions. Another frequent abnormality was hy-
podontia of the second praemolars. Many of
the patients had proclination of the upper
incisors. ,
FIGURE 1. The measurement points and planes em-ployed.
TABLE 1. Traits of dental occlusion in 16 patientswith mulibrey nanism
Characteristic Proportion
Class I occlusion 16/16Normal overbite 16/16Crowding of upper dental arch, 9/16>»4mm
Crowding of lower dental arch, 6/16>»4mm
Proclined permanent upper incisors 6/15(>18D)
Hypodontia of one or several second 5/16bicuspids
Overjet >3mm 4/14Lateral cross bite 2/16Lateral scissor bite 1/16
Visual inspection of the mulibrey patientsrevealed a characteristic facies: triangular fa-cial shape, ocular hypertelorism, and a broadand deep nasal bridge (Figures 2 and 3).
In lateral cephalograms (Figure 4), theskulls appeared long in relationship to thedelicate facial structures. Frontal "bossing"was evident. The nuchal plane of the occipitalbone seemed to lie horizontally, but the an-gulation of the lambdoid suture to the cranialbase structures appeared normal.
Myllarniemi et al., Murisrey Nanism SynpromE 371
In most of the patients the frontal andsphenoidal sinuses were either totally absentor were clearly smaller than what was consid-ered normal for age (Table 2). In six of the 16cephalograms the nasal bones were found tobe in a vertical position and close to themedial orbital wall. Both the position and theappearance of the sella turcica were abnor-mal. The posterior cranial base seemed to beshort and the cranial base angle large.
The tongue appeared small in relationship
FIGURE 2. Facial appearance of patients with mulibrey nanism aged 24, 17, 14, 8, 7 and 5.
372 Cleft Palate Journal, October 1978, Vol. 15 No. 4
FIGURE 3. Profile appearance of the same patients.
Myllarniemi et al., Murisrey Nanism Synproms 373
FIGURE 4. Lateral cephalograms of the same mulibrey patients as in Figures 2 and 3. Note characteristic formofsella, short clivus, long foramen magnum, frontal bossing, small frontal and sphenoidal sinuses, obtuse gonial angleand horizontal nuchal plane. Vertical nasal bones in the patients at top right and middle left.
374 Cleft Palate Journal, October 1978, Vol. 15 No. 4
TABLE 2. Characteristics of skull structure in nor-
mal lateralis of 16 patients with mulibrey nanism
Characteristic Proportion
Long, shallow sella turcica 15/16Missing or small frontal sinus 13/16Missing or small sphenoidal sinus 14/16Horizontal nuchal plane 12/16
Frontal "bossing" 11/16Relatively small tongue 10/16Vertical nasal bone 6/16
Small maxillary sinus 4/16
to the oral cavity in most instances. The hyoid
bone could not be detected in all of the films,
but in several patients, it was abnormally
high, close to the mandibular border.
Results of linear and angular measure-
ments are presented graphically in Figure 5.
The linear dimensions were generally smaller
than the age- and sex-specific means for Fin-
nish children and young adults (Koski 1960,
Aantaa and Koski 1962, Koski 1965, Koski-
nen and Koski 1965). The only exceptions
were the lengths of the skull and foramen
magnum. The clivus, b-s, was relatively the
shortest dimension measured. The ratio be-
tween the two cranial base components, n-
s/b-s, was clearly abnormal. Its range in these
patients was 1.5 to 2.5, whereas, in a normal
population, the value is close to 1.5 at all age
levels (Koski, 1960).
In contrast to the linear dimensions, the
angular measures tended to be larger than the
reference means. The ranges for the angles
foramen plane/clivus, nasal floor/mandibu-
lar base plane, and mandibular base/ramus
tended to be large. On the other hand, the
distribution of the angles clivus/sphenoidal
plane and foramen plane/nasal floor were
fairly close to normal.
Discussion
The recentlydiscovered new form of pre-
natal growth failure which has been named
mulibrey nanism (Perheentupa et al., 1970)
appears to entail several peculiar cranio-facial
features. So far the number of known affected
individuals is rather small, and the cranio-
facial features observed in these individuals
are so diversified that clear-cut typification in
this respect is not yet possible. Nevertheless,
some of the findings seem to merit discussion.
From the purely dental point of view, the-
only abnormally frequent findings were
crowding of teeth and hypodontia of the sec-
ond bicuspid. The former finding may be
associated with the smallness of the jaws,
whereas the latter feature remains unex-
plained.
The absence or smallness of frontal sinuses
when correlated with the frontal "bossing"
can perhaps be explained in terms of "func-
tional craniology" (Moss and Young, 1960).
Protection of the eye-balls from above does
not, in these individuals, depend on the out-
ward growth and concomitant pneumatiza-
tion of the frontal bone immediately above
the orbits. On the other hand, the deficiency
of the sinuses, including the sphenoidal sinus,
may be an infantile trend (vide infra). 'A depressed nasal bridge is a feature of
several craniofacial malformations involvingcartilage disorders. Whether its occurrence insome of these patients can be similarly ex-plained cannot be determined at the presenttime.The relatively high position of the hyoid
bone in many of these patients, in conjunctionwith the horizontally positioned nuchal plane,prompts the question as to whether it indi-cates relative shortness of the neck region and,if so, whether this contributes to the typicalhigh-pitched voice of the mulibrey-patients(Perheentupa et al., 1970). Further studies are
needed to answer these questions.Among the generally smaller than normal
cranial dimensions, the lengths of the skulland the foramen magnum are interesting ex-ceptions. The normality of the latter dimen-sion can be taken as an indication of normalgrowth at the circumforaminal synchon-droses. Thus a generalized growth disturbancein the chondrocranial cartilage tissues, as seenin achondroplasia, appears to be ruled out.The normal length of the brain capsule incontrast to the subnormal lengths of the com-ponents of the skull base and the face seemsto indicate that adequate space for the brainhas been obtained by compensatory growthof the calvarium, which bulges in both thefrontal and occipital regions.The peculiar shape of the sella turcica is
typical of this syndrome (Perheentupa et al.,1970). It resembles the shape of the bonysphenoid before the cartilaginous dorsum sel-lae has ossified, a process which normally .
F/C
- 5 -~4 - 3-2-1 - 1 +41 +2 +3 +4 +5
- 71- 6 - 5 - 4 - 3 - 2 - 4 +1 +2 e e-1 +1 + 2 +3 + 4 + 5
ns/sb
+ 1 +2 - 1 + 1 + 2 + 3 + 4 + 5
& oie-7- 6 - § -4 - 3 - 2-1 - 100 +1 +2+3 +4 +5
-7- 6-5-4 - 3 - 2-4 - 10 +1 +2+3 +4 +5
o-id
-7-6-5-4 +2 -1 [+1 +4 +5
gl - op
|___]- 2-1 +1+2+3+4 +5
-T-6-5-4 - 3 - 2 -d
FIGURE 5. Deviation of the linear and angular cephalometric measurements from the normal mean in SD units.The lowest columns represent one patient.
375
376 Cleft Palate Journal, October 1978, Vol. 15 No. 4
takes place gradually after five years of age
(Latham, 1972). If ossification is delayed in
these patients, the shortness of the clivus is
also explained by another infantile feature,
the low position of the sellar fossa.
Some of the angular relationships also in-
dicate a lag in development. At birth, the
angle between the foraminal plane and the
clivus is large, and the clivus normally
straightens up during postnatal growth
(Kummer, 1952; Koski, 1960). The skull base
angle, nasio-sella-basion, is large during late
fetal life (Kvinnsland 1969), and its abnor-
mally skewed distribution towards the large
side in the present series could be viewed as
due to persistence of an early structural fea-
ture.
The facial appearance of the mulibrey pa-
tients resembles patients affected with another
prenatal growth disorder, the Silver-Russell
syndrome (Silver et al., 1953; Russell, 1954;
Tanner et al., 1975). In this condition, the
face is also triangular, and the neuro-cranium
appears large. Teeth erupt normally and form
severely crowded dental arches (Silver and
Gruskay, 1957; Silver, 1959; Rossier, 1962;
Silver, 1964). No cephalometric descriptions
are available of the craniofacial features of
Silver-Russell patients. Inspection of pub-
lished pictures (Lassker and Reich, 1969) and
our own observations on three patients show
normal sella and normal cranial base struc-
tures while the discrepancy between the facial
and cranial parts is even more pronounced.
In progeria, a growth disorder in which the
affected child resembles an aged person, the
characteristic facies results from retardation
of facial growth in the presence of normal
growth of the neurocranium (Rosenthal et al.,
1956).
Looked upon as a whole, in mulibrey pa-
tients, the shape of the skull and the size
relationship between the skull and the face
resemble those seen normally in newborn and
young infants A tempting interpretation,
therefore, is that the characteristic facies is the
result of lagging development of the craniofa-
cial skeleton. This interpretation would at
least be in accord with the generalized growth
disturbance seen in this syndrome (Perheen-
tupa et al., 1973). We hope that longitudinal
studies of young patients will clarify the na-
- ture of the craniofacial abnormalities.
References
AANTAA, S. aAnp Kosk1, K. Rontgenologis-kefalometrinentutkimus eraiden kallonpohjan ja kitalaen tasojen kes-kinaisista suhteista ikavuosina 6-16 poikkeleikkausai-neiston valossa, Suom Hammaslaak Toim, 58, 145-151,1962. .
ALVvESALO, L., The influence of sex chromosome genes ontooth size in man, Proc. Finn. Dent. Soc., 67, suppl. IV,1971.
Cumminc, G. R., Kerr, D., anp Fercuson, C. C., Con-strictive pericarditis with dwarfism in two siblings(mulibrey nanism),J. Pediatr., 88, 569-572, 1976.
Gorm, R. J., PmmpBorc, J. J., anp ConEn, M. M., JR.,Syndromes of the head and neck. 2nd edition. NewYork; McGraw-Hill, 1976, 757-758.
Haavikko, K., The formation and the alveolar andclinical eruption of the permanent teeth., Proc. Finn.Dent. Soc., 66, 103-170, 1970.
Kosk1, K., Some aspects of the growth of the cranial base'and the upper face, Odont. Tidskr., 68, 344-357, 1960.
Kosk1, K., Roentgen-cephalometry on anatomical basis,Studieweek, 1965, 73-80, 1965.
KoskinEn, L., anp Kosk:, K., Ortodontiassa kaytetta-vaksi soveltuva diagnostinen rontgenkefalometrinenanalyysimenetelma, -Suom -Hammaslaak -Toim, 61,409-416, 1965.
KummEr, B., Untersuchungen liber die ontogenetischeEntwicklung des menschlichen Schadelbasiswinkels, ZMorphol Anthrop., 43, 331-360, 1952.
KvinnsLAND, S., The profile of the foetal facial skeleton,Doctoral thesis, University of Bergen, 1969.
LaTHAM, R. A., The sella point and postnatal growth ofthe human cranial base, Am. ]. Orthod., 61, 156-162,1972.
LasskEr, G., anp RreicH, J., Das Russell-Sydrom-eineForm des kindlichen Zwergwuchses, Arch. Kinderheilk,178, 303-315, 1969.
Moss, M., anp Younc, R. A., Functional approach tocraniology, Am. J. Phys. Anthrop., 18, 261-292, 1960.
PERHEENTUPA, J., AutiO, S., Leist:, S., Anp Rata, C.,Mulibrey nanisms: dwarfism with muscle, liver, brainand eye involvement, Acta. Paediatr. Scand., 59, suppl.206, 74-75, 1970.
PErHEENTUPA, J., Autio, S., LEist1, S., RartTa, C., ANDTuuTER1I, L., Mulibrey nanism, an autosomal recessivesyndrome with pericardial constriction, Lancet ZI,351-355, 1973.
RANTANEN, A., Suomalaisten hampaiden suuruussuht-eesta, Suom Hammaslaak Toim, 60, 250-262, 1964.
RosEntHaAr, I. M., BronstEm, P., DarrenBachH, F. D.,Pruzansxy, S., anp RosEnwaLp, A. K., Progeria, Re-port of a case with cephalometric roentgenograms andabnormally high concentrations of lipoproteins in theserum, Pediatrics, 18, 565-577, 1956.
RossiEr, A., Nanisme '"intra-uterin'" avec dysostosecranio-facio mandibulaire, Arch. Fr. Pediatr., 19,561-579, 1962.
RussELL, A., Syndrome of "intra-uterine" dwarfism rec-ognizable at birth with cranio-facial dysostosis, dispro-portionately short arms, and other anomalies (5 ex-amples), Proc. R. Soc. Med., 47, 1040-1044, 1954.
Siver, H. K., Kivasu, W., GroroE, J., anp DEamER, W.C., Syndrome of congenital hemihypertrophy, short-ness of stature, and elevated urinary gonadotropins,
Myll@rniemi et al., MuuriBrEy Nanism Synproms 377
1964. '
TannEr, J. M., Lejarraca, H., anp CAMERON, N., The
natural history of the Silver-Russell syndrome: a lon-
Pediatrics, 12, 368-375, 1953.
Siver, H. K., anp GruskAy, F. L., Syndrome of congen-
ital hemihypertrophy and elevated gonadotropins: Oc-
currence in a seven-year-old boy, Am. J. Dis. Child., 93, gitudinal study of thirty-nine cases, Pediatr. Res., 9,
611-623, 1975.559-560, 1957. .Siver, H. K., Congenital asymmetry, short stature, and THOREN, L., The so-called mulibrey nanism with pericar-
elevated urinary gonadotropin, Am. J. Dis. Child., 97, dial constriction, Lancet II, 731, 1973.768-773, 1959. Voornrss, M. L., Husson, G. S. anp Brackman, M. S.,
Growth failure with pericardial constriction, Am. J.SirveEr, H. K., Asymmetry, short stature, and variationsin sexual development, Am. J. Dis. Child., 107, 495-515, Dis. Child., 130, 1146-1148, 1976.