adult-syndrome: an autosomal-dominant disorder with pigment anomalies, ectrodactyly, nail dysplasia,...
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American Journal of Medical Genetics 45:642-648 (1993)
ADULT-Syndrome: An Autosomal-Dominant Disorder With Pigment Anomalies, Ectrodactyly, Nail Dysplasia, and Hypodontia
Peter Propping and Klaus Zerres Institut fur Humangenetik, Universitat Bonn, Germany
We describe a family with at least seven living persons who are affected by an hitherto unde- scribed autosomal-dominant syndrome with variable expression, bearing close resem- blance to the EEC syndrome and related dis- orders. The main manifestations are hypo- dontia and/or early loss of permanent teeth, ectrodactyly, obstruction of lacrimal ducts, onychodysplasia, and excessive freckling. We propose the acronym ADULT (acro-der- mato-ungual-lacrimal-tooth)-syndrome for this condition. o 1993 wiley-~iss, Inc.
KEY WORDS: EEC syndrome, ectodermal dysplasia, ADULT syndrome
INTRODUCTION We report on a family with a disorder characterized by
excessive freckling, ectrodactyly, nail dysplasia, hypo- dontia and/or early loss of permanent teeth, neuroder- mitic signs, obstruct lacrimal ducts, and hypoplastic nipples. As an acronym we propose ADULT-syndrome: acro-dermato-ungual-lacrimal-tooth-syndrome (Fig. 1).
CLINICAL DESCRIPTION Skin and Hair
Intensive freckling is a regular sign of the syndrome (Table I, Figs. 2-11), convincingly reported also in most of the deceased relatives who were affected, but not in the unaffected family members. The freckles are typ- ically shaped in most affected individuals but may also be unusually large (IV/2, IV/6, and V/2). Several af- fected males (III/lO, IV16, IV/lO, and V/1) as well as the female index case of the family (IV/2) have hypoplastic nipples and breasts, respectively. Axillary hair tends to be sparse (IV/2). The hair of the head is thin and is lost from the thirties on, even in female IV/8. All the affected
Received for publication May 28, 1992; revision received Au- gust 23, 1992.
Address reprints request to Prof. Dr. P. Propping, Institut fur Humangenetik, Universitat Bonn, Wilhelmstrasse 31, D-5300 Bonn 1: Germany.
0 1993 Wiley-Liss, Inc.
individuals show typical neurodermitic signs, including exfoliative dermatitis of fingers and toes.
Hands and Feet The degree of malformation of hands and feet varies
largely. It ranges from typical ectrodactyly (111110, Fig. 12) to absence of one finger (IV12) and osseous or cutane- ous syndactyly (111/3, IV/6, and V/1) to normally formed fingers and toes. Most affected members of the family have dysplasia of finger and toe nails; IV12 and V12 have only watch glass nails.
Teeth Some patients reported primary hypodontia of perma-
nent teeth and others had a normal number of teeth. Beginning in teenage, permanent teeth are being lost probably due to weak fixation. Enamel is normal.
Body proportions, sweating, vision, and hearing of the affected individuals are normal. Skin pigmentation upon sun exposure is normal. There is no CNS dysfunc- tion and intelligence is normal.
DISCUSSION Despite striking similarities to the EEC-syndrome
and related conditions, major phenotypical differences in this family allow us to define an hitherto undescribed new syndrome.
Table I1 shows the characteristic manifestations in the EEC syndrome and in the described family. Common manifestations to both conditions are ectrodactyly, which shows a relatively mild expression in most af- fected persons in this family; fine, thin, dry, smooth skin; sparse, thin hair; and onychodysplasia. Both con- ditions share hypodontia which is markedly expressed in this family. Hypoplastic or absent nipples as well as tear duct abnormalities can also be found in both condi- tions. Despite these similarities marked differences are also present. In the EEC syndrome cleft lip/palate is a main manifestation which can be found in more than 70% of patients [Rodine and Richieri-Costa, 19901. None of our patients showed a cleft lip or palate or any related microsymptom.
Excessive freckling and loss of permanent teeth usu- ally before the age of 25 years in our family are not known in the EEC syndrome. Eczematous changes in
TAB
LE I
. C
linic
al S
ims
of t
he A
ffec
ted
Fam
ily M
embe
rs
Sex
Age
at
Frec
klin
g Fr
onta
l alo
peci
a N
ail d
yspl
asia
Neu
rode
rmiti
c sig
ns
Han
d m
alfo
rmat
ion
exam
inat
ion
(yea
rs)
Foot
mal
form
atio
n
Obs
truc
t lac
rim
al
Hyp
odon
tia
Loss
of
perm
anen
t
duct
teet
h
1111
3 II
I/10
IVl2
IV
l6
IV18
IV
110
VI1
v1
2 M
59
+ +++ + +++
Rig
ht o
sseo
us
synd
acty
ly
314 L1
left
: cu
tane
ous
synd
acty
ly
314
-
(+I
-
21 y
ears
M
44
+++
+++
++
++
Ect
roda
ctyl
y of
bo
th h
ands
Rig
ht:
synd
acty
ly
314
L, l
eft:
abse
nce
of
2nd
toe,
sy
ndac
tyly
31
4 + -
20 y
ears
F 28
+++
Watch
glas
s na
ils ++
R
ight
abs
ence
of
3rd
fing
er
Rig
ht:
cuta
neou
s sy
ndac
tyly
11
2
+ O
ngoi
ng L
, 14
te
eth
left
M 24
+++ + + -
-
Lef
t: cuta
neou
s sy
ndac
tyly
21
3
+ - O
ngoi
ng L, 5
F 33
++
+ + + -
Rig
ht: 2
nd t
oe
smal
ler + +
M
M
M
29
5 2
+ ++
-
++
+
-
- +
+ W
atch
gla
ss
++
+ +
- L
eft:
-
cuta
neou
s sy
ndac
tyly
3 I
4
nails
-
Lef
t: cuta
neou
s sy
ndac
tyly
3 I
4
25 y
ears
O
ngoi
ng L
1 10
N
ot a
pplic
able
N
ot a
pplic
able
G
et hl
eft
teet
h le
ft
*The
num
ber o
f the
cro
sses
( + t
o + +
+ ) i
s a ro
ugh
esti
mat
e of
the
seve
rity
of th
e re
spec
tive
sign
. In
Vl2
it c
ould
not y
et b
e de
cide
d w
heth
er h
e w
ill d
evel
op th
e sy
ndro
me.
644 Propping and Zerres
I
D O 6 m
11 12 13
1v
3 L 5 6 V
1 2
Fig. 1. Pedigree of the family. @, Pigment anomalies; @, Nail anomalies; Q, Malformations of hands and/or feet;O, Affected, details unknown; @, Hypodontia and/or early loss of permanent teeth;?, Question- able feature
Fig. 2. Hands of IIII3 with right syndactyly 314 and nail dysplasia.
Fig. 3. a. Hands of IIII10 with ectrodactyly. b. Feet of IIIllO with syndactyly 314 on both sides and absence of 2nd toe of the left foot. Note also nail dysplasia.
ADULT Syndrome 645
Fig. 4. a. Hands of IVI8 with nail dysplasia. b. Feet of IV/8 with nail dysplasia. Note the small 2nd toe of the right foot.
Fig. 5. Facial appearance of IVilO (29 years). Fig. 6. Feet of IVI6 with left syndactyly 2/3 and nail dysplasia.
Fig. 7. a. Hands of the proposita IV/2 with absence of 3rd finger of the right hand and watch glass nails. b. Feet of IV12 with right syndactyly 1/2 and nail dysplasia.
646 Propping and Zerres
Fig. 8. Feet of VI1 with left syndactyly 314 and nail dysplasia.
Fig. 10. Freckling in IVIG.
Fig. 9. Freckling and hypoplastic breasts in IVI2.
skin, which are markedly expressed in our family, have been observed in patients with hypohidrotic ectodermal dysplasia but not in the EEC syndrome.
In addition, there are several descriptions of single families sharing certain features with our family: Robinson et al. [19621 described five individuals from three generations of a family with delayed primary and secondary dentition, missing or misshapen teeth, small dystrophic nails, syndactyly of toes 1,2,3, and 4, postax- ial polydactyly, and sensorineural deafness.
Freire-Maia [19701 described brother and sister with hypotrichosis of scalp and body hair, absent or small, abnormally shaped teeth, hypoplastic or absent nails,
Fig. 11. Freckling and hypoplastic nipples in VI1.
hypohidrosis, prominent lips with an incomplete cleft in one case, prominent simple ears and limb reduction as well as dry, shiny, wrinkled skin, and hypoplastic nipples.
Tsakalakos et al. [19861 reported mother and daugh- ter from a large autosomal-dominant pedigree. The main findings were hypotrichosis (with trichorrhexis
ADULT Syndrome 647
Fig. 12. a. Radiograph of right hand of III/lO. Hypoplastic 3rd metacarpal bone, absence of 3rd phalange. Syndactyly 1/2. b. Radiograph ofleft hand ofIII/lO. Hypoplastic 3rd metacarpal bone, absence of 3rd phalange. c. Radiograph of right foot of IIUlO. d. Radiograph of left foot of IIUlO. Hypoplastic 2nd metatarsal bone, absence of 2nd toe. Syndactyly 3/4.
648 Propping and Zerres
TABLE 11. Main Findings in the EEC Syndrome and the Present Familv
Ectrodact ylyl syndact yly
Nail dysplasia Sparse, thin hair Fine, thin, smooth
Excessive freckling Eczematous skin
changes Hyperkeratosis Tear duct
abnormalities Early loss of
permanent teeth Abnormal nipples Deafness Cleft lip/palate Hypodontia Mental retardation Small or malformed
auricles Genitourinary
anomalies
skin
EEC syndrome
+ + + +
+ +
Present family
+ + + + + +
+
nodosa) hypodontia, focal linear dermal hypoplasia of the nose, hyperpigmentation of the skin, absent breasts, ridged finger-nails and dysplastic toe-nails, and mild sensorineural deafness.
Boudghene-Stambouli and Merad-Boudia [19911 re-
ported a family with five affected sibs of consanguineous parents (first cousins) with manifestations of hypohidro- tic ectodermal dysplasia (e.g., hypotrichosis, hyper- keratosis, onychodysplasia, and “spread pointed small teeth”). All affected children as well as one maternal aunt showed syndactylies of varying degree. One pa- tient showed freckling, which was not mentioned in other affected persons.
In spite of some similarities with previously described conditions, this family has sufficiently distinctive mani- festations to warrant the definition of a new syndrome.
ACKNOWLEDGMENTS The authors are grateful to Ismet Ovuc for excellent
photographical work. The valuable suggestions of Pro- fessor Frank Majewski/Diisseldorf and Dr. Wolfgang Kuster/Marburg are highly appreciated.
REFERENCES Boudghene-Stambouli 0, Merad-Boudia A (1991): Association dyspla-
sie ectodermique et syndactylie. Ann Dermatol Venereol 118: 107-110.
Freire-Maia N (1970): A newly recognised genetic syndrome of tetra- melic deficiencies, ectodermal dysplasia, deformed ears, and other abnormalities. Am J Hum Genet 22:370-377.
Robinson GC, Miller JR, Bensimon JR (1962): Familial ectodermal dysplasia with sensorineural deafness and other anomalies. Pedi- atrics 30:797-802.
Rodini ESO, Richieri-Costa A (1990): EEC syndrome: Report on 20 new patients, clinical and genetic considerations. Am J Med Genet 37:42-53.
Tsakalakos N Jordaan FH, Taljaard S, Hough SF (1986): A previously undescribed ectodermal dysplasia of the tricho-odonto-onychial subgroup in a family. Arch Dermatol 122:1047-1053.
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