American Journal of Medical Genetics l5:67-70 (1983)

Trichoodontoon ych ial Dysplasia-A New Meso-Ectodermal Dysplasia

Marta Pinheiro, Newton Freire-Maia, and Alcyone J. Roth

Department of Genetics (M. P., N.E-M.) and Department of Surgery (A.J. R.), Federal University of Parana, Curitiba, Brazil

We describe a hitherto apparently undescribed ectodermal dysplasia in four sib- lings. The condition combines severe hypotrichosis, hypoplasia of enamel leading to secondary anodontia, dystrophic nails, supernumerary nipples, nevus pigmen- tosus, bone deficiency of the fronto-parietal region, and other anomalies. This condition is probably due to an autosomal-recessive gene.

Key words: dysplasia, ectodermal dysplasia, trichoodontoonychial dysplasia, autosomal recessive inheritance, hypotrichosis, enamel hypoplasia, hypodontia, dystrophic nails, super- numerary nipples, skull deficiency

INTRODUCTION

Ectodermal dysplasias sensu lato form a large group of disorders with 11 subgroups [Freire-Maia, 1971, 19771. So far, a total of 99 different clinical conditions leading to a total of 108 entities due to heterogeneity have been classified into this group [Freire-Maia and Pinheiro, 19831. About 40% of them are pure ectodermal dy splasias, the remaining being dysplasia/malformation syndromes. This paper pre- sents an apparently hitherto undescribed ectodermal dysplasia of the trichoodonto- onychial subgroup.

FAMILY AND CLINICAL DATA

The condition was present in four women (one died at 3 years) belonging to a sibship of eight women and five men. The parents, who were normal, deny consan- guinity but they were born in the same small town (Espinosa) in the extreme north of the state of Minas Gerais, Brazil. Therefore, the possibility of distant consanguinity between them is plausible.

The pregnancies and births were normal. The 4th pregnancy among the 14 terminated as a spontaneous abortion. The pregnancy order of the patients is 3rd, 5th, 9th, and loth (the proposita).

Received for publication July 2, 1982; revision received December 18, 1982

Address reprint requests to Dr. Marta Pinheiro, Depto. de Genttica, UFPR, Caixa Postal 3357, 8oooO Curitiba, PR, Brazil.

0 1983 Alan R. Liss, Inc.

68 Pinheiro, Freire-Maia, and Roth

When the proposita was 16 years old, the following measurements were ob- tained: height-1.48 m, weight-49.0 kg, innercanthal distance-3.2 cm, outercanthal distance-8.7 cm, interpupillary distance-6.0 cm, head circumference-53 .O cm. With exception of shortness, the measurements are within normal limits.

The proposita had an extensive area of alopecia on the top of the head with only a peripheral fringe of hair in the temporal and occipital regions, where the hair was dry, brittle, and sparse. She had a skull deficiency measuring 6 X 8 cm in the fronto- parietal region (corrected by costal bone and skin grafts, and flap rotation of skin). This region was also traumatically altered. Eyebrows, lashes (Fig. l ) , and axillary teeth. Both finger- and toenails presented variable degrees of dystrophy (Fig. 2). They were brittle and did not require cutting; some toenails were yellowish or brownish. A large number of pigmented nevi were present on the skin (especially on face and back) (Fig. 1). She also had mild palmoplantar hyperkeratosis, and mild xeroderma on limbs, more pronounced on legs. Dermatoglyphics: right hand-five ulnar loops with extensive ridge dissociation; atd angle: 48"; Walker index: 16.7%; interdigital pattern 14; hypothenar pattern A"; thenar pattern 0. Left hand: three ulnar loops (11, IV, and V) and two arches (I and 111) also with extensive ridge dissociation; atd angle: 42" ; Walker index: 11.7 % ; absent interdigital pattern; hypothenar pattern A"; thenar pattern 0. Both palmar regions also showed ridge dissociation. Menarche, pubarche, and thelarche occurred at age 12.

Audiometric examination: normal hearing on the right but mixed hearing loss on the left ( - 55 decibels). Left external auditory meatus ended blindly.

Her affected sisters had similar manifestations, but, since their scalps were not traumatically altered, it was possible to verify more clearly that their usual changes are ephelides, actinic keratosis, papules, and crusts (Fig. 3). Both sisters had extra- numerary nipples: three very rudimentary ones in one patient (one below the left normal mamma and one near each axilla) and one below each mamma (one of them with areola) in the other patient. The two sisters were edentalous owing to enamel hypoplasia, were also short for their age (1.45 m and 1.48 m respectively at 22 and 24 years), and had normal hearing and fewer nevi than the proposita. The demato- glyphics of both affected sisters also showed an extensive palmar and digital ridge dissociation making it impossible to diagnose most finger patterns; they possibly had a high number of arches (low TRC). The eldest affected sister also presents fronto- parietal skull deficiency similar to that of the proposita.

Normal findings: face, eyes, sweating capacity, neurological status, intelligence, ECG, locomotor apparatus, genitalia, general health, and chromosomes (with G- banding technique).

DISCUSSION

The trichoodontoonychial subgroup to which this pure ectodermal dysplasia belongs now consists of 23 conditions [for a review of 18 of them, see Pinheiro et al, 19811. The others, not mentioned in that paper, are odontoonychodysplasia with alopecia [Pinheiro and Freire-Maia, 198 11, Schinzel-Giedion syndrome [Schinzel and Giedion, 1978; Donnai and Harris, 19791, dwarfism-alopecia-pseudoanodontia-cutis laxa [Epps et al, 1977; Wajntal et al, 1982; Da Silva, personal communication, 19821, ectodermal dysplasia with syndactyly [Wiedemann et al, 19781, and the present condition, for which we propose the name trichoodontoonychial dysplasia. It is certainly different from all the other 22 conditions.

As signs of the dysplasia now being described, the following may be accepted: generalized hypotrichosis, alopecia at the parietal region, enamel hypoplasia leading to

Trichoodontoonychial Dysplasia 69

Fig. 1 . The proposita at 16 years.

Fig. 2. The nails of the proposita.

Fig. 3 . Two sisters of the proposita.

70 Pinheiro, FreireMaia, and Roth

anodontia, onychodystrophy, fronto-parietal bone deficiency and skin manifestations (nevi, ephelides, papules, mild xeroderma on limbs, mild palmoplantar keratosis, ex- tranumerary nipples, abnormal dermatoglyphics). Studies on other patients are neces- sary for a better delineation of this meso-ectodermal dysplasia and to verify whether short stature and hearing loss are components or merely coincidental findings.

Cause is unknown but probably genetic. A gonial autosomal-dominant mutation in one of the parents or an autosomal-recessive gene present in heterozygous state in both of them are plausible hypotheses. However, the latter is more acceptable since, in spite of not being close relatives, the parents were born in the same small and certainly endogamic community of the interior of Brazil. The uncorrected segregation ratio (9:4) is closer to 3: l (x2 = 0.35) than to 1:l (x2 = 1.92), although the data agree with both ratios. The corrected segregation ratio (with exclusion of the propos- ita) (9:3) corresponds exactly to a 3: 1 ratio. The fact that only women are affected in a sibship of eight women and five men may be accepted as coincidental.

ACKNOWLEDGMENTS

We are very grateful to Dr Cecilia Le Bars for calling our attention to the proposita, and to Drs A.A. Gattermann Jr, and F. Laynes de Andrade, as well as to other members of the staff of University Hospital, for their valuable cooperation and for the care they gave the proposita. One of us (A.J.R.) performed four autoplastic grafts of skin and costal bone, and Dr Gattermann performed three dressings with amniotic membrane on the patient. We also thank Dr NCria A. Maia €or the analysis of the dermatoglyphics and Miss Irene Sedoski for expert secretarial assistance.

This research was supported by the Conselho Nacional de Desenvolvimento Cientifico e TecnoMgico (CNPq and PIG-FINEP) and by the World Health Organi- zation. The authors are Research Fellows of CNPq.

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Edited by John M. Opitz