American Journal of Medical Genetics 36:161-166 (1990)

Brief Clinical Report

New Cases of Dermoodontodysplasia? Marta Pinheiro, Floriano Peixoto Gomes-de-Sa-Filho, and Newton Reire-Maia Department of Genetics (MP. , N.F.-M.) and Department of Pharmacology (FP.G.-S.-F.), Federal University of Parana, Curitiba, Parana, Brasil

We report on 2 sisters and one brother with severe dental anomalies, trichodysplasia, on- ychodysplasia, and slight skin alterations. Four other relatives have only mild dental anomalies. Differential diagnosis includes 3 other ectodermal dysplasias: hypodontia and nail dysgenesis, dermoodontodysplasia, and trichodermodysplasia with dental altera- tions. Cause is unknown.

KEY WORDS: ectodermal dysplasia, dental anomalies, trichodysplasia, onychodysplasia, skin alter- ations

INTRODUCTION Contrary to a generalized opinion held up to the end of

the 1960s when the term ectodermal dysplasia desig- nated either one or a few conditions, ectodermal dyspla- sias are now known to encompass a large number of conditions. About half of them have a genetic cause; in some of these conditions, the genetic cause is well estab- lished, whereas for others the hypotheses derive from suggestions. For a full analysis of the problem, see Freire-Maia [1971, 19771 and Freire-Maia and Pinheiro [1984, 1987, 19881.

Here we describe a pure ectodermal dysplasia of the tricho-odonto-onychial subgroup. Differential diagnosis between this condition and 3 others will be discussed.

FAMILY HISTORY The father is of German origin whereas the normal

mother is of mixed Danish and German origin. They deny consanguinity. The couple had 3 children (F, M, F). The parents’ ages at the birth ofthe children were 26,28, and 29 years (mother) and 29,31, and 32 years (father), respectively.

The father lacked one upper lateral incisor. The pater- nal grandmother had extranumerary teeth (not spe- cified). One paternal cousin (a woman) had no upper

Received for publication November 14, 1988; revision received October 19, 1989.

Address reprint requests to Dr. Marta Pinheiro, Depto. de Ge- netica, UFPR, Caixa Postal 19071, 81504 Curitiba, PR, Brasil.

0 1990 Wiley-Liss, Inc.

lateral incisors, and her brother had extranumerary teeth. One paternal first cousin once removed (a woman) was reported as having had only deciduous teeth. (At age 18 years they were replaced by dentures.) With the exception of this woman, all the other differentially af- fected persons belong to the same family line.

CLINICAL REPORTS Patient 1

P.A. (Fig. 1) is a girl born a t term on April 12, 1971, after a normal pregnancy and delivery. She is the first- born. Birth weight and length (not recorded) were ac- cepted as within normal ranges.

At birth, she was noted to have hip dislocation; thin, dry, and brittle scalp hair; and dry skin.

On examination at age 1510/i2 years she was a healthy girl with a height of 1.70 m and a weight of 58.5 kg. Her scalp hair was thin, dry, and brittle, with several structural alterations (longitudinal grooves and depres- sions, scalings and bead-like swellings) as shown by SEM analysis of hair shafts (Fig. lb-d); fragile and brittle finger- and toenails; dry skin with scaling (mostly on arms and legs), and splittingon heels (mainly during winter). Her teeth were analysed both clinically and on the basis of an orthopantomogram (Fig. la) a t age l6%2 years. She had persistence and hypodontia of deciduous teeth, lower peg-shaped incisors, apparent anodontia of permanent teeth, presence of a peg-shaped extranumerary tooth in 2 or (the mother reports that a deciduous tooth was present a t this place), hypo- plastic maxilla and mandible, and total crossbite. It is not known whether the extranumerary tooth is a de- ciduous or a permanent one. Dental formula, assuming the extranumerary tooth is a deciduous one in D:

Letters denote primary teeth present.

Patient 2 M.A. (Fig. 2) is a boy born a t term on June 13, 1973,

after a normal pregnancy and delivery. At birth, he was similar to his sister (Patient 11, except for hip disloca- tion.

At 138/i2 years examination showed a healthy boy with a height of 1.69 m and a weight of 60.0 kg. SEM

162 Pinheiro et al.

--- A B C - - -- 3 0 T 2 8 R Q P

Fig. 1. Orthopantornogram and SEM analysis of hair shafts of Patient 1. For details, see text.

- -H I J --16L O N M 2 l K l 9 - -

analysis of scalp hair shafts showed dystrophic bulbs, scaling, and longitudinal depressions (Fig. 2b-e); the finger- and toenails were fragile and brittle (bilaterally dysplastic on fingers I1 and toes V). His teeth were also analysed both clinically and on the basis of an orthopan- tomogram at age 1 4 / 2 years (Fig. 2a). There was a persistence of deciduous teeth, hypodontia of deciduous and permanent teeth, rudimentary tooth bud in 2- 116, taurodontism in w, and hypoplastic maxilla and mandible. Dental formula, assuming the presence of the rudimentary tooth bud in 16:

Letters denote primary teeth present; numbers denote permanent teeth present.

Patient 3 J.A. (Fig. 3) is a girl born at term on December 16,

1974, after a normal pregnancy and delivery. At birth she was similar to her sibs (except for hip dislocation, present only in Patient 1).

At 1 2 % ~ years she was a healthy girl with a height of 1.49 m and a weight of 45.0 kg. Her scalp and body hair were similar to those of her sibs except for frizzy scalp hair. SEM analysis of hair shafts showed longitudinal depressions and grooves, dystrophic bulbs, and scaling (Fig. 3b-d).

Her toenails were fragile and brittle (the fingernails were normal); the skin alterations were similar to those of patients 1 and 2. Dental analysis (also on the basis of a clinical examination and an orthopantomogram) at age 13 years documented persistence of deciduous teeth, hypodontia of deciduous and permanent teeth, and hy-

New Cases of Dermoodontodysplasia? 163

-L- A B C D - --- T 2 8 R - P R

Fig. 2. Orthopantornogram and SEM analysis of hair shafts of Patient 2. For details, see text.

-- H I J - - - DISCUSSION - N M 2 l K - - - The condition here described presents similarities to 3

other ectodermal dysplasias among 36 conditions

poplastic maxilla and mandible (Fig. 3a). Dental for- mula:

Normal findings (all 3 patients): general health, body hair, sweating, skeletal system, genitalia, psychomotor development, dermatoglyphics, hearing, eyes and face.

164 Pinheiro et al.

Fig. 3. Orthopantomogram and SEM analysis of hair shafts of Patient 3. For details, see text.

[F’reire-Maia and Pinheiro, 19871 belonging to the same (tricho-odonto-onychial) subgroup of F’reire-Maia’s [1971, 19771 classification. They are hypodontia and nail dysgenesis [Witkop, 1965; Hudson and Witkop, 19751, dermoodontodysplasia [Pinheiro and Freire- Maia, 19831, and trichodermodysplasia with dental al- terations [Pinheiro et al., 19861. Table I shows a sum- mary of the signs of the above-mentioned dysplasias

(including the present one). An analysis of Table I shows that conditions 2 and 4 present the highest degree of similarity (0.801, whereas the others show degrees of similarities equal to or lower than 0.60, as follows: 1-3- 0.32, 1-2-0.36, 1-4-0.48, 2-3-0.56, and 3-4-0.60. [The degree of similarity between 2 conditions is ob- tained by dividing the number of concordantsimilar or identical-signs by the total number of investigated

New Cases of Dermoodontodysplasia? 165

TABLE I. Comparison Among Previously Described Similar Conditions and the Present One*

Hypodontia and nail dysgenesis [Witkop, Dermoodontodysplasia Trichodermodysplasia 1965; Hudson and [Pinheiro and Freire- with dental alterations

Witkop, 19751 Maia, 19831 [Pinheiro et al., 19861 This paper Findings ~~~~ 1 2 3 4 Synonyms McK No. No. of families No. of cases Sex Hair

Fine Thin and brittle scalp

hair Irregular and sparse

eyebrows and lashes Sparse axillary and

pubic hair Slow growing Dry Structural changes Circumscribed &ea of

alopecia a t the top of the head

Craniofacial Hypodontia Cone-shaped teeth Supernumerary teeth Microdontia Hypoplastic maxilla

and mandible Everted lower lip Frontal bossing Straight nasal bridge Recurrent epistaxis

Dry and thin espe- Skin

cially on palmoplan- tar regions

Dry with scaling and splitting

Palmoplant ar keratoses

Simian crease Sparse and small caf6-

au-lait spots Nails

Small, thin, and spoon shaped

Longitudinal ridging Slow growth Dysplastic and brittle

Cause

Tooth and nail dysplasia 18,950

6 29

11 F, 18 M

+ -

+ ? - -

+ + + + -

+ + + -

+ + + - AD

*The reasons for not including Weech [1929; second case], Redpath and Winter [1969l, and Giansanti et al. [1974] in hypodontia and nail dysgenesis are referred to in Hudson and Witkop [1975] and Freire-Maia and Pinheiro [19841. AD = autosomal dominant; XD = X-linked dominant.

signs (in our case, 25). This is a simple procedure since a more complex one-ascribing different weights to differ- ent signs-would require a better clinical knowledge of all the conditions.]

Close similarities between conditions are not an indi- cation of identity. Even clinically identical patients may have different (causally) entities, while patients with somewhat different constellations of signs may have the same condition due, for instance, to a gene with variable expressivity (cf. F’reire-Maia and Pinheiro, 1984, pages

15-19; McKusick, 1989, page xx). With these basic principles, only clinical similarities between patients within the same family may serve as a guarantee that we are dealing with the same (causal) condition. Therefore, the act of jumping or splitting conditions may reflect much more a “philosophy” of the investigator than something coming obligatorily from the facts.

With the above degrees of similarity, we can only repeat what these degrees reveal: dermoodontodys- plasia and the present condition are very similar (in 80%

166 Pinheiro et al.

of the analysed signs) as compared with the other con- sidered conditions (whose similarity varies from 32% to 60%). So, we may either assume that all of them are different entities or identify our present dysplasia with dermoodontodysplasia. However, note 1) that dermo- odontodysplasia is clearly due to a fully penetrant auto- soma1 dominant gene whereas the cause of our present dysplasia is unknown and 2) that the 4 relatives of the 3 above-described patients present only dental alter- ations; these dental alterations could be due to a differ- ent cause.

If the present dysplasia proves later to be a different condition, we would suggest the name hair-tooth-nail (HATOONA) dysplasia for it.

ACKNOWLEDGMENTS We are most grateful to Prof. Robin Mario Hofmeister

(Center of Electronic Microscopy; our University) and Dr. Guaraci A. Furtado Robert, from the Institute of Technology of Parana (TECPAR), for the SEM analysis of hair shafts; two anonymous reviewers for their excel- lent criticisms; Miss Irene Sedoski for typing the manu- script; and CNPq (Brasilia) and WHO (Geneva) for f i - nancial assistance. M.P. and N.F.-M. are research fellows of CNPq.

REFERENCES Freire-Maia N (1971): Ectodermal dysplasias. Hum Hered 21:

309-312.

Freire-Maia N (1977): Ectodermal dysplasias revisited. Acta Genet Med Gemellol (Roma) 26:121-131.

Freire-Maia N, Pinheiro M (1984): “Ectodermal Dysplasias: A Clinical and Genetic Study”. New York: Alan R. Liss, Inc.

Freire-Maia N, Pinheiro M (1987): Ectodermal dysplas iasA review of the conditions described after 1984 with an overall analysis of all the conditions belonging to this nosologic group. Rev Bras Genet 10:403-414.

Freire-Maia N, Pinheiro M (1988): Selected conditions with ectodermal dysplasia. In Salinas CF, Opitz JM, Paul NW (eds): “Recent Ad- vances in Ectodermal Dysplasias.” BD:OAS XXIV(2):109-121.

Giansanti JS, Long SM, Rankir, J L (1974): The “tooth and nail” type of autosomal dominant ectodermal dysplasia. Oral Surg Oral Med Oral Pathol 37:576-582.

Hudson CD, Witkop CJ, J r (1975): Autosomal dominant hypodontia with nail dysgenesis. Oral Surg Oral Med Oral Pathol39:409-423.

McKusick VA (1989): “Mendelian Inheritance in Man. Catalogs of Autosomal Dominant, Autosomal Recessive. and X-Linked Phe- notypes.” 8th ed. Baltimore: The Johns Hopkins University Press.

Pinheiro M, Freire-Maia DV, Miranda E, Silva-Filho OG, Freire-Maia N (1986): Trichodermodysplasia with dental alterations: An appar- ently new genetic ectodermal dysplasia of the tricho-odonto- onychial subgroup. Clin Genet 29:332-336.

Pinheiro M, Freire-Maia N (1983): Dermoodontodysplasia: An eleven- member, four generation pedigree with an apparently hitherto un- described pure ectodermal dysplasia. Clin Genet 24:58-68.

Redpath TH, Winter GB (1969): Autosomal dominant ectodermal dys- plasia with significant dental defects. Br Dent J 126:123-128.

Weech AA (1929): Hereditary ectodermal dysplasia (congenital ecto- dermal defect). A report of two cases. Am J Dis Child 37:766-790.

Witkop CJ, Jr (1965): Genetic disease of the oral cavity. In Tiecke RW (ed): “Oral Pathology.” New York: McGraw-Hill, p 786.