American Journal of Medical Genetics 3:35-41 (1979)

Autosomal Dominant Inheritance of Scalp Defects With Ectrodactyly R.P. Bonafede and P. Beighton

Department of Human Genetics, Medical School, University of Cape Town, South Africa

Nine members of four generations of a kindred had an autosomal dominant syndrome in which congenital scalp defects were associated with abnormali- ties of the hands and feet. Radiographically apparent, circumscribed defects of the skull were an additional inconsistent feature. Genetic counseling is made difficult by varying phenotypic expression of the gene.

Key words: scalp defect, digital hypoplasia, ectrodactyly

INTRODUCTION

Kindreds with a dominantly inherited syndrome in which congenital scalp defects were associated with anomalies of the distal portions of the limbs have been reported by Adams and Oliver [1945], Scribanu and Temtamy [1975], and Burton, Hauser and Nadler [1976].

African family, and our findings have been documented in order to provide a perspec- tive of the range of manifestations of this disorder. The variability of expression of the gene poses difficult problems in genetic counseling.

We have investigated nine affected individuals in four generations of a South

CASE REPORT

The proband, a 26-year-old female, sought genetic counseling in 1976 because she had congenital malformation of the feet. The second to fifth toes were very hypoplastic, being represented by residual stumps of soft tissue. The first toes were shortened and laterally deviated and bore dystrophic curved nails (Fig 1). Gait was virtually normal, but the patient had never been able to indulge in dancing or athletics. The fingers were

Received for publication January 13, 1978; revision accepted and edited by Dr. Holmes,May 31,1978.

Address reprint requests to Professor P. Beighton, Dept of Human Genetics, Medical School, Observa- tory 7925, CapeTown, South Africa.

0148-7299/79/0301-0035$01.70 @ 1979 Alan R . Liss, Inc.

36 Bonafede and Beighton

Fig 1. The feet of the proband (right) and her affected brother (left).

shortened and tapered but function of the hands was not impaired (Fig 2). The crown of the head bore a bald patch of white, hard scar tissue, 2 cm in diameter. Physique and in- telligence were normal and no abnormalities were detected in any other system.

or absent and that the metatarsals were hypoplastic (Fig 3). In the hands, shortening was especially evident in the terminal phalanges, although the others were affected to a lesser extent (Fig 4). The skull and the rest of the skeleton were unremarkable.

Radiographic studies confirmed that the phalanges of the toes were rudimentary

Fig 2. The hands of the proband (right) and her affected brother (left).

Inheritance of Scalp Defects With Ectrodactyly 37

Fig 3 . Anteroposterior radiograph of the proband’s feet. The phalanges of the 2nd-5th toes are rudi- mentary and the metatarsals are hypoplastic.

Fig 4. Anteroposterior radiograph of the hands of the proband. The terminal phalanges are shortened.

38 Bonafede and Beighton

Cytogenetic investigations and routine laboratory screening of blood and urine yielded normal results.

THE KINDRED

The proband’s maternal grandfather, who died at the age of 80, had similar abnor- malities of the hands and feet. In addition, an area of the scalp on the vertex, approxi- mately 10 cm in diameter, was composed of hairless scar tissue. These hand and scalp changes were evident in old family photographs. This individual, who was of British stock, had emigrated to South Africa at the turn of the century. His own parents and seven older siblings were said to have been normal.

Her toes were stubby but her scalp was normal. The brother of the proband (111-4), age 23, had gross malformation of the forefeet and short fingers. His scalp was normal.

An uncle (11-4), who had died at the age of 48 from myocardial infarction, was said to have had short fingers and toes, with dystrophic nails, and a large scalp defect. His 17- year-old daughter (111-9) was found to be similarly affected.

An affected aunt (11-l), age 58, had mild shortening of the fingers and toes, with a normal scalp. The granddaughter, aged one year (IV-3), had changes of greater severity in the extremities, together with an irregular scar-like scalp defect 5 X 7 cm in diameter over the vertex.

Radiographs of the hands and feet were obtained in each of the six living affected kin. The changes conformed to the clinical appearances; some degree of hypoplasia or absence of the phalanges of the toes, defective modeling of the metatarsals, and shorten- ing of the terminal phalanges of the fingers was evident in every individual (Fig 5).

Skull radiography in patient 11-2 revealed an irregular calvarial defect, approxi- mately 2 X 3 cm in diameter, in the midline of the vertex (Fig 6). However, her scalp was normal. (By contrast, the proband had a scarred scalp and a normal calvarium.) Patient IV-3, the proband’s infant cousin, had an abnormally large anterior fontanelle and an overlying scalp defect. The skull of the proband’s aunt, patient 11-1, was normal, as was her scalp.

None of the affected individuals had any other abnormalities of the skin, lips, palate, or lacrimal ducts. Each enjoyed good general health and had a normal physique.

All living members of the kindred were examined and investigated. In addition to the proband, six of the individuals in three generations were found to be affected. Objec- tive evidence permitted confirmation of the diagnosis in two other deceased relatives. The pedigree is shown in Figure 7.

The proband’s mother (11-2), age 50, had short tapering fingers with hooked nails.

DISCUSSION

The syndrome consists of abnormalities of the extremities, together with defects of the scalp and calvarium. The affected kindred had neither platolabial involvement nor changes in the lacrimal ducts, and the condition is clearly distinct from the dominantly inherited ectrodactyly-ectodermal dysplasia syndromes, in which these features are additional components [Temtamy and McKusick, 1969; Weigmann and Walker, 1970;

Inheritance of Scalp Defects With Ectrodactyly 39

Fig 5 . Anteroposterior radiograph of the feet of the proband’s brother.

Fig 6. Anteroposterior radiograph of the skull of the proband’s mother. A small irregular defect is evi- dent in the calvarium, but the overlying scalp was normal.

40 Bonafede and Beighton

I

I

II 3

Fig 7. The pedigree of the kindred.

Bixler et al, 19721 . The isolated split-hand and split-foot syndromes, which may be in- herited as autosomal dominants or autosomal recessives [Verma et al, 19761, are distin- guishable by the lack of skull and scalp involvement and by the different pattern of the anatomical defect in the extremities. In the patients with severe abnormalities in the feet, the presence of rudimentary digits permitted differentiation from the Streeter amniotic band deformity.

The pattern of distribution of the syndrome in the kindred which we studied is consistent with autosomal dominant inheritance and, as the affected grandfather was the youngest of a large sibship, it is possible that he represented a new mutation of the abnor- mal gene. The clinical features were very variable and, although the changes in the feet were always more severe than those in the hands, the size of the scalp lesions bore no relationship to the degree of involvement of the extremities. Defects of the calvarium were an additional inconsistent feature, recognizable only on radiographic study. These latter changes were not necessarily related to overlying scalp defects, and these r b nor- malities were each encountered independent of one another.

The association of scalp defects and distal limb anomalies had been previously re- corded in eight individuals in three generations of a hndred in Minnesota [Adams and Oliver, 19451 , in three individuals in two generations [Scribanu and Temtamy, 19751 , and in four members of three generations of a Spanish-American family [Burton, Hauser and Nadler, 19761 . In each of these kindreds, expression was variable, and in the family studied by Scribanu and Temtamy [ 19751 a generation had been skipped. However, an isolated scalp defect did not occur as the sole manifestation of the abnormal gene in any of these reported families, or in the subjects whom we studied. The kindred investigated by Adams and Oliver [ 19451 was noteworthy for the severity of the changes; several individuals had gross abnormalities of the hands, and at least three had absence of the feet.

countered by Scribanu and Temtamy [ 19751 , makes genetic counseling of such families a difficult matter. The problem is compounded by the gross malformations present in the family studied by Adams and Oliver [ 19451. If it is accepted that the conditions in these

The variability of clinical expression and the possibility of nonpenetrance ~ as en-

Inheritance of Scalp Defects With Ectrodactyly 41

families are genetically identical, a risk exists that any infant inheriting the abnormal gene will have severe abnormalities of the extremities. Although none of the affected indi- viduals in the kindred that we studied was seriously handicapped, guidance concerning further generations must necessarily be circumspect. In the future, it is possible that feto- scopy may have a part to play in the management of the situation.

ACKNOW L E DGM EN TS

We are grateful to Mr. C. Clow and Mrs. S. Henderson for the illustrations and to

The investigation was supported by grants from the University of Cape Town Staff Mrs. Gillian Shapley for typing the manuscript.

Research Fund and the South African Medical Research Council.

REFERENCES

Adams H, Oliver CP (1945): Hereditary deformities in man due to arrested development. J Hered

Bixler D, Spivack J , Bennett J, Christian JC (1972): The ectrodactyly-ectodermal dysplasia clefting

Burton BK, Hauser L. Nadler HL (1976): Congenital scalp defects with distal limb anomalies. J Med

Scribanu N, Temtamy SA (1975): The syndrome of aplastic cutis congenita with terminal, transverse

Temtamy S, McKusick VA (1969): Synopsis of hand malformations with particular emphasis on

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(EEC) syndrome. Clin Genet 3:43-51.

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Verma IC, Joseph R, Bhargava S, Mehta S (1976): Split-hand and split-foot deformity inherited as an

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