A LARGE FAMILY WITH TYPE IV RADIAL POLYDACTYLY From the A. SEYHAN, N. AKARSU and E KESKIN Department of Plastic and Reconstructive Surgery, CelalBayar University, Manisa, (TUBITAK) DNA/Cell Bank and Gene Research Laboratory, Hacettepe University, Ankara and the Municipality Hospital, Izmir, Turkey This study examines one of the largest pedigrees with radial polydactyly type IV (uncomplicated polysyndactyly) comprising a total of 69 individuals, of whom 26 have been affected over six generations. Typical manifestations of the pedigree were bilateral radial and ulnar digital duplications, as well as syndactyly between the middle and ring fingers and the second and third toes. There was no craniofacial anomaly in any of the 17 cases examined physically. This observation suggests that radial polydactyly type IV and Greig craniofacial-synostosis syndrome with similar digital manifestations are clinically-distinct entities. Journal of Hand Surgery (British and European Volume, 1998) 23B." 4:530-533 Polydactyly and syndactyly are common digital malfor- mations which occur alone or in combination with other malformations in a variety of syndromes (Upton, 1990). Efforts have been made to classify polydactyly and syn- dactyly, however no satisfactory classification has been made so far. According to a widely used classification (Temtamy and McKusick, 1978), polydactyly can be divided into two groups, preaxial and postaxial, now known as radial and ulnar. Radial polydactyly can be further classified into four subtypes. Among all of these subtypes, radial polydactyly type IV (uncomplicated polysyndactyly) is the only subtype which manifests polydactyly and syndactyly simultaneously (Temtamy and McKusick, 1978). Bilateral duplication of the thumb as well as syndactyly between the middle and ring fingers are the characteristic features of hands with uncompli- cated polysyndactyly. In the lower limbs, syndactyly can affect all toes, especially the second and third, and is associated with partial or complete duplication of the first and second toes. Some families exhibit fifth digit polydactyly in hands and feet. No craniofacial abnor- mality has been observed in this type. It is inherited in an autosomal dominant pattern with full penetrance (Temtamy and McKusick, 1978). The digital changes are identical to those of Greig cephalopolysyndactyly syn- drome, which demonstrates polysyndactyly with cranio- facial dysmorphism. It has therefore been suggested that Greig syndrome and radial polydactyly type IV might be due to the same genetic aetiology (Baraitser et al, 1983). The other isolated polysyndactyly phenotypes (i.e., syn- polydactyly, crossed polydactyly and complex polysyn- dactyly with triphalangeal thumb) should also be considered on differential diagnosis of radial polydactyly type IV (Nicolai and Hamel, 1988; Sayli et al, 1995). Genetic linkage and gene cloning techniques have provided a new approach to classifying poly- and/or syn- dactylies on a molecular level. Synpolydactyly (syn- dactyly type II) and Greig cephalopolysyndactyly syndrome have been mapped to chromosomes 2q31 and 7p13, respectively (Pettigrew et al, 1991; Sarfarazi et al, 1995). Further studies have revealed that the GLI3 gene is responsible for the Greig cephalopolysyndactyly phenotype and that synpolydactyly malformation is due to a mutation on the HOXD13 gene (Akarsu et al, 1996; Vortkamp et al, 1991). Familial complex polysyndactyly with triphalangeal thumb has been linked to the chromo- some 7q36 region, where the triphalangeal thumb locus has been mapped (Heutink et al, 1994; Tsukurov et al, 1994). To date, neither a chromosomal locus nor a gene has been identified for radial polydactyly type IV. We report a six-generation Turkish kindred manifest- ing typical digital changes of radial polydactyly type IV without craniofacial abnormality. In this family of 69 individuals, 26 were affected. MATERIALS AND METHODS The pedigree consists of 69 individuals of whom 26 were affected in six generations (Fig 1). Seventeen family members including six affected persons had died by the time of the study. We examined 30 family members (17 affected) and obtained X-rays from five affected indi- viduals, with approval from the Celal Bayar University Ethical Committee (Table 1). Physical examinations were completed with the emphasis on hand and foot manifes- tations as well as craniofacial findings. Three individuals, numbers 35, 59 and 66 on the pedi- gree in Figure l, have been operated on for syndactylies by the first or last authors using opposing triangular flaps and full-thickness skin grafts. Case 35 has also been treated for a double thumb on the left hand by the Bilhaut-Cloquet procedure. RESULTS Clinical findings are summarized in Tables 2 to 4. One person (number 43 on the pedigree in Figure 1) has been arbitrarily chosen for a detailed description of the clini- cal findings (Fig 2). The proband was a 28-year-old man who was affected by radial as well as ulnar polydactyly in both hands. Rudimentary, boneless extra skin tags next to the little fingers were removed when he was young. On the left hand, there was a partial soft tissue syndactyly between the middle and ring fingers, and the thumb was incompletely duplicated (Fig 2a). The latter is seen as a central hole in the X-ray, which is the most consistent 530