American Journal of Medical Genetics 36:l-6 (1990)

Autosomal Dominant Tibial Hemimelia-Polysyndactyly-Triphalangeal Thumbs Syndrome: Report of a Brazilian Family

A. Richieri-Costa, E. de Miranda, T.Y. Kamiya, and D.V. Freire-Maia LaboraMrio de Gene'tica Humana, Hospital de Pesquisa e Reabilita@o de LesBes Labio-Palatais, USP, Bauru, SP, Brazil.

We report on 3 persons in a 3-generation Bra- zilian family affected with complex limb de- fects. The spectrum of limb anomalies ranged from isolated toe syndactyly to severe bilat- eral tibial aplasia. Radioulnar synostosis was present in 2 of the 3 patients. Clinical and genetic aspects are discussed.

KEY WORDS: tibial hemimelia-polysyndac- tyly-triphalangeal thumbs syndrome, tibial developmen- tal field, autosomal dominant inheritance

INTRODUCTION Tibial hemimelia has been described as a teratologic

disruption [Lenz and Knapp, 19621; it has been seen in chromosomal aberrations [Christianson and Nelson, 19841 and in kinships or sibships with an autosomal dominant or recessive pattern of inheritance [Carraro, 1931; Takahashi et al., 1968; Eaton and McKusick, 1969; Sandrow et al., 1970; Fried et al., 1977; Temtamy and McKusick, 1978; Wiedemann and Opitz, 1983; Ma- jewski et al., 1985; Richieri-Costa, 1987; Richieri-Costa, 1988; Richieri-Costa et al., 1987a,bl.

Few cases of the autosomal dominant tibial hemime- lia-polysyndactyly-triphalangeal thumbs syndrome have been reported previously [Melde, 1892; Werner, 1915; Reber, 1967/1968; Eaton and McKusick, 1969; Pashayan et al., 1971; Yujnovsky et al., 1974; Lamb et al., 19831. Here we report on this syndrome in 3 mem- bers of a Brazilian family. Clinical and genetic aspects of the tibial hemimelia-polysyndactyly-triphalangeal thumbs syndrome are discussed.

Received for publication September 8, 1987; revision received September 13, 1989.

Address reprint requests to A. Richieri-Costa, Laboratorio de Genetica Humana, Hospital de Pesquisa e Reabilitaqko de Lesiies Labio-Palatais, USP, PO Box 620, 17043 Bauru, SP, Brazil.

0 1990 Wiley-Liss, Inc.

CLINICAL REPORTS Patient 1 KFI (IV-8) (Figs. 1, 21, the proposita, was

born in 1981. She was the first child of a 24-year-old mother and a 26-year-old father. Pregnancy was normal. Delivery was through cesarean section at term. Birth- weight (BW) was 3,200 g, length (TBL) was 47 cm, and occipitofrontal circumference (OFC) was not recorded. Upper and lower limb anomalies were noted at birth. Neuropsychological development was normal.

At age 5 years, a supernumerary phalangeal comple- ment of finger IV, a proximal syndactyly between fin- gers I11 and IV at right, and supernumerary preaxial toes were surgically removed.

Examination at age 7 years showed an intelligent girl. Height was 118 cm (50th centile), weight 25.4 kg (75th centile), and OFC 51.5 cm (50th centile). She presented 5 triphalangeal fingers bilaterally; surgical scars be- tween fingers I11 and IV on the right (Fig. 3); limited pronation, supination, and extension a t the elbows; short and abnormally modeled right leg; and preaxial polydactyly of both feet.

The results of routine laboratory blood tests and of cytogenetic studies were normal. Roentgenograms showed bilateral radioulnar synostosis (Fig. 4), abnor- mally modeled carpal bones (hamate and capitate coali- tion), 5 triphalangeal digits (Fig. 51, hypoplastic right tibia represented by a proximal and a distal abnormally modeled bony fragment, laterally displaced fibula, ab- normally shaped tarsal bones (Fig. 61, and a broad meta- tarsal I a t right (Fig. 7).

Patient 2 FA1 (111-7) (Fig. 8), the proposita's father, was 26 years old. Pregnancy, gestational antecedents, and delivery were stated as normal. BW, TBL, and OFC were not recorded. Upper and lower limb anomalies were noted at birth. Neuropsychological development was normal. A left supernumerary preaxial triphalan- geal finger was removed a t an early age.

Examination at age 26 years showed an intelligent man with hypoplastic and syndactylous right fingers I and 11, hypoplastic left finger I with absent nail, se- verely hypoplastic left toe I, and medially deviated right toe I with increased distance between toes I and 11.

The results of routine laboratory blood tests were nor- mal. Roentgenograms showed hypoplastic radii; dhypo-

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Fig. 1. Pedigree. ., Tibial hemimelia-polysyndactyly-triphalan- geal thumbs syndrome; 0 , preaxial polysyndactyly of feet.

Fig. 2. Patient 1

plasia of the styloid apophysis; bilaterally abnormally modeled carpal bones with coalition between lesser mul- tangular, greater multangular, hamate, and capitate; synostosis between the greater multiangular and meta- carpal I a t left; abnormally modeled left metacarpal I and I1 with hypoplastic and fused phalanges of finger I; and long and hypoplastic right metacarpal I with a hy-

poplastic triphalangeal complement (Fig. 9). He also had a broad and abnormally modeled left metatarsal I with 3 undifferentiated and rudimentary bone comple- ments distally placed, and broad metatarsal and proxi- mal phalanx of right toe I with one undifferentiated bone distally placed to the distal phalanx (Fig. 10).

Patient 3 AD1 (111-10) (Fig. 111, the proposita’s uncle, was 19 years old. Pregnancy, gestational antecedents, and delivery were normal. BW, TBL, and OFC were not recorded. Upper- and lower-limb anomalies were noted at birth. Neuropsychological development was normal.

Examination at age 19 years showed an intelligent young man with bilateral 5-finger hands; hypoplastic and syndactylous fingers IV and V a t right (Fig. 12); limited pronation, supination, and extension of the el- bows, markedly at left; short and grossly abnormally modeled legs with both fibulae laterally placed through the knee; abnormally modeled feet; and bilateral foot polydactyly (Fig. 13).

The results of routine laboratory blood tests were nor- mal. Roentgenograms showed proximal radioulnar syn- ostosis a t left (Fig. 141, bilateral multiple coalitions be- tween the carpal bones and bilateral synostosis between the greater multangular and metacarpal I, bilaterally abnormally placed triquetrum, bilaterally hypoplastic metacarpal I with hypoplastic triphalangeal comple- ment, and syndactyly between right fingers I and I1 (Fig. 15). Bilateral tibial aplasia with bowed and superi- orly placed fibulae, bilateral medially and vertically deviated calcaneus, bilateral abnormally modeled tar- sal bones with multiple coalitions, long and hypoplastic metatarsals; left metatarsals I and I1 were fused, and there were 5 proximal phalanges in the right foot and 6 in the left foot (Figs. 16, 17).

Familial Antecedents Patient 111-5 was personally examined and presented

preaxial polysyndactyly of both foot. Radiological exam- ination was not performed. Patient 11-2 was referred by several members of the family as having “triphalangeal thumbs” and short lower limbs. No radiological data was available. Patients 1-1, 1-2 and 11-3 were referred as having no related abnormalities. No radiological data were available.

DISCUSSION Tibial hemimelia-polysyndactyly-triphalangeal

thumbs syndrome was first reported by Melde 118921. Reber [196711968] reported the first instance of autoso- ma1 dominant inheritance with incomplete penetrance. Since then, 5 other families have been reported [Eaton and McKusick, 1969; Pashayan et al., 1971; Yujnovsky et al., 1974; Temtamy and McKusick, 1978; Lamb et al., 19831.

The clinical spectrum of the tibial hemimelia-poly- syndactyly-triphalangeal thumbs syndrome shows marked inter- and intrafamilial variation, ranging from isolated triphalangeal thumbs to triphalangeal thumbs, handlfoot polysyndactyly, and absentlhypoplastic tib- iae. Triphalangeal thumbs and foot polydactyly were the most frequent findings in upper and lower limbs, respec- tively, while hand oligodactyly was least common [Re-

Fig. 4. Radiological aspects of the elbows of patient 1.

Fig. 3. Hands of patient 1.

Fig. 5. Radiological aspects of the hands of patient 1.

Fig. 6. Radiological aspects of the lower limbs of patient I Fig. 7. Radiological aspects of the feet of patient 1.

4 Richieri-Costa et al.

Fig. 8. Patient 2.

Fig. 9. Radiological aspects of the hands of patient 2.

ber, 1967/1968]. Radioulnar synostosis was reported in one instance [Pashayan et al., 19711; patient IX/8 of Reber's report also had this type of involvement, show- ing limitation of elbow movement. In the present report, radioulnar synostosis was present in patients 1 and 3 and can be accepted as a valuable sign of this syndrome.

Autosomal dominant inheritance was demonstrated in all familial cases; skipping of a generation was ob- served in 4 instances [Reber, 196711968; Temtamy and McKusick, 1978; Lamb et al., 1983; present case], favor- ing incomplete penetrance. Males and females are af- fected similarly. Male-to-male transmission was ob- served in 2 instances [Reber 1967/1968; Lamb et al., 19831.

As for genetic counseling purposes, the risks can be stated as follows: (1) maximally 50% to the offspring of affected patient (considering K ranging from 0.5 to 1.0); (2) maximally 8.6% at a penetrance of 60% to the un- affected person with one affected parent (or assumed carrier) [Aylsworth and Kirkman, 1979; Otto and F'rota- Pessoa, 19791; and (3) maximally 12.5% a t a penetrance of 50% after an isolated case [Frota-Pessoa et al., 19761.

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Carraro A (1931): Assenza congenita delle tibia e sordomutismo nel quatro fratelli. Chir Organi Mov 16:429-438.

Christianson AI, Nelson MM (1984): Four cases oftrisomy 18 syndrome with limb reduction malformations. J Med Genet 21:293-297.

Eaton GO, McKusick VA (1969): A seemingly unique polydactyly-syn- dactyly syndrome in four persons in three generations. The First Conference on The Clinical Delineation of Birth Defects. Part 111: Limb Malformations. Baltimore: Alan R. Liss, Inc., for the National Foundation-March of Dimes. BD:OAS V (3):221-225.

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Fig. 10. Radiological aspects of the feet of patient 2.

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Fig. 16. Radiological aspects of the right leg of patient 3. Fig. 17. Radiological aspects of the left leg of patient 3.

Frota-Pessoa 0, Otto PA, Olivares Plaza H J r (1976): The variation of recurrence risks with penetrance for isolated cases of autosomal dominant conditions. J Hered 67:256.

Lamb DW, Wynne-Davies R, Whitmore JM (1983): Five-fingered hand associated with partial or complete tibial absence and pre-axial polydactyly. A kindred of 15 affected individuals in five genera- tions. J Bone Joint Surg 65B:60-63.

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Wiedemann HR, Opitz JM (1983): Unilateral partial tibial defect with preaxial polydactyly, general micromelia and trigonomacrocephaly with a note on “developmental resistance.” Am J Med Genet 14:467-472.

Yujnovsky 0, Ayala D, Vincitorio A, Viale H, Sakate N, Nyhan WL (1974): A syndrome of polydactyly-syndactyly and triphalangeal thumbs in three generations. Clin Genet 6:51-59.