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.