J Med Genet: first published as 10.1136/jmg.13.5.394 on 1 October 1976. Downloaded from Journal of Medical Genetics (1976). 13, 394-398. Family study of inherited syndrome with multiple congenital deformities: symphalangism, carpal and tarsal fusion, brachydactyly, craniosynostosis, strabismus, hip osteochondritis V. VENTRUTO, R. DI GIROLAMO, B. FESTA, A. ROMANO, G. SEBASTIO, and L. SEBASTIO From Dipartimento di Ematologia degli Ospedali Riuniti di Napoli, Servizio di Immunopatologia e Genetica Ematologica, Naples; and Dipartmento di Ematologia degli Ospedali Riuniti di Napoli, Divisione di Ematologia, Naples; Servizio di Radiologia degli Ospedali Riuniti di Napoli, Naples, Italy Summary. A syndrome of brachydactyly (absence of some middle or distal phalanges), aplastic or hypoplastic nails, symphalangism (ankylosis of proximal interphalangeal joints), synostosis of some carpal and tarsal bones, craniosynostosis, and dysplastic hip joints is reported in five members of an Italian family. It may represent a previously undescribed autosomal dominant trait. Brachydactyly and symphalangism are well- hands and feet (Fig. 2-5). They varied in severity, andcopyright. known hereditary anomalies of the hands and feet. the malformations were not symmetrical in all affected individuals The nails various In brachydactyly, digits or specific phalanges may (Appendix). presented degrees of dystrophy (including total absence), solely on be affected, sometimes in association with shorten- the brachydactylous fingers, while they appeared normal ing of metacarpal and metatarsal bones, and classi- where there was symphalagism without brachydactyly fication has been based on specific patterns (Bell, (IV.4). All five individuals showed craniosynostosis, 1951). The thumbs and big toes are not usually hip dysplasia, and pes planus, and had pain on walking. involved. There may be various degrees of dys- The least affected family member is IV.4 who had sym- http://jmg.bmj.com/ plasia of the nails (Cuevas-Sosa and Garcia-Segur, phalangism and clinodactyly, but lacked brachydactyly, 1971). Symphalangism is the result of failure of had normal nails, and showed partial craniosynostosis. differentiation of the interphalangeal joints, and Hip dysplasia in 11.7 caused a severe joint dislocation. The stature, weight, and intelligence are normal in all leads to ankylosis between proximal or, more subjects. III.1 and his daughter IV.1 showed stra- rarely, distal interphalangeal joints. Other con- bismus, but there was no defect of vision or hearing. genital anomalies may be associated with sym- Laboratory data were normal including serum calcium, phalangism, the most common ofwhich is synostosis serum phosphorus, and serum phosphatase. The of the carpal and tarsal bones. on September 28, 2021 by guest. Protected We report here five cases in three generations of a I syndrome of brachydactyly with symphalangism, 2 and other features including craniosynostosis. This may be a hitherto undescribed autosomal IIA O b dominant trait. 2 3 4 5 b 7 8 9 Family study The propositus, III.3, was first seen because of acute flAffected / P leukaemia, and the bone anomalies were observed in four other members ofher family in three generations (Fig. 1). Unaffected'U / The anomalies were in the hip, the and both IV Propositus cranium, 1 2 3 4 Received 11 December 1975. FIG. 1. 394 J Med Genet: first published as 10.1136/jmg.13.5.394 on 1 October 1976. Downloaded from Family study of inherited syndrome with multiple congenital deformities 395 I r T I IVr1 copyright. J3~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~..... http://jmg.bmj.com/ electroencephalogram was also normal, as were the Discussion pattem of the sensitive organs. A normal karyotype was The only syndrome in which symphalangism and seen on two affected individuals (II.7 and III.1) by occur is that described banding techniques. The markers brachydactyly together by following genetic Haws (1963), classified by McKusick (1975) as were examined: adenylate kinase, malate dehydrogenase, on September 28, 2021 by guest. Protected phosphohexose isomerase, phosphoglucomutase, adeno- type C brachydactyly; in that instance affected indi- sine deaminase, phosphoenolpyruvate, aspartate trans- viduals showed deformity of the middle and proxi- aminase, alanine transaminase, diaphorase. Unfor- mal phalanges of the second and third fingers, tunately, no information regarding linkage was obtained hyperphalangy (hypersegmentation of the proximal from these data. phalanx), brachymetapody, and symphalangism; Dermatoglyphic patterns showed some unusual they lacked anomalies of the hips and cranium. features, including: absence of some digital triradii and Robinson et al (1968) reported a kindred con- an increase in the axial triradius angle; a type 'epsilon' sidered the authors to show C configuration by D-line exit in III.3; characteristic pat- by type brachydac- terns on the brachydactylic fingers; the absence of flexion tyly, in which affected individuals had brachy- creases at interphalangeal joints; the presence of tri- dactyly and Legg-Perthes disease of the hip, but no radius in some of these areas; and the high incidence of symphalangism or craniosynostosis. whorls. There were no patterns in the thenar or hypo- The syndrome described here shows more wide- thenar areas. spread bony anomalies than others of this general J Med Genet: first published as 10.1136/jmg.13.5.394 on 1 October 1976. Downloaded from 396 Ventruto, Di Girolamo, Festa, Romano, G. Sebastio, and L. Sebastio copyright. i r ... FIG. 3. http://jmg.bmj.com/ on September 28, 2021 by guest. Protected FIG. 4. J Med Genet: first published as 10.1136/jmg.13.5.394 on 1 October 1976. Downloaded from Family study of inherited syndrome with multiple congenital deformities 397 great toes are unaffected. To our knowledge, strabismus and craniosynostosis have not been de- scribed before in connexion with symphalangism and/or brachydactyly. As for the dysplasia of hip joints, it is noteworthy that the femoral heads appeared to be normal; the anomaly involved the acetabular structure (osteochondritis). The hip abnormality is, therefore, distinct from that de- scribed by Robinson et al, in which the changes were similar to those of Perthes' disease (osteochon- dritis of the capital femoral epiphysis). The distribution in the pedigree is consistent with an autosomal dominant trait, with some varia- tion in gene expressivity. It may have arisen as a new mutation in generation I. The authors thank Dr Silvana Santachiara, Laboratorio di Genetica Biochimica ed Evoluzionistica di Pavia, for her help in the study of genetic markers, and Dr D. M. Bannerman, Division of Medical Genetics, State Uni- versity of New York at Buffalo, for his advice and criti- cism of the manuscript. REFERENCES Bell, J. (1951). On brachydactyly and symphalangism. In Treasury of Human Inheritance, Vol. 5, p. 1. Cambridge Uni- versity Press, London and New York. Cuevas-Sosa, A. and Garcia-Segur, F. (1971). Brachydactyly with absence of middle phalanges and hypoplastic nails. Journal of copyright. Bone andJ7oint Surgery, 53, 101-105. Haws, D. V. (1963). Inherited brachydactyly and hypoplasia of the bones of the extremities. Annals of Human Genetics, 26, 201-211. 1,. 5. McKusick, V. A. (1975). Mendelian Inheritance in Man, 4th ed., p. 43. The Johns Hopkins Press, Baltimore. type reported The disorder is Robinson, G. C., Wood, B. J., Miller, J. R., and Baillie, J. (1968). previously. located Hereditary brachydactyly and hip disease. journal of Pediatrics, both in hands and feet, though the thumbs and 72, 539-543. http://jmg.bmj.com/ Appendix overleaf. on September 28, 2021 by guest. Protected J Med Genet: first published as 10.1136/jmg.13.5.394 on 1 October 1976. Downloaded from 398 Ventruto, Di Girolamo, Festa, Romano, G. Sebastio, and L. Sebastio .4 I.. 0 .4 4I 0 .44 ^. 0 E 0 0! 04 0 0 0 Co O 13 ,;a 00e 0 .CF 0 0 W >. a44 0 0.0- IE >4 >4 >4 >4 0 U ) (Au. 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