Original article 161 Ulnar/fibular ray defect and brachydactyly in a family: a possible new autosomal dominant syndrome E ´ va Morava a , Marta Czako ´ b , Judit Ka ´ rteszi a , Beatrix Cser a , Karen Weissbecker c and Karoly Me ´ hes a,b The ulnar-mammary syndrome (MIM 181450) includes postaxial ray defects, abnormalities of growth, delayed sexual development, and mammary and apocrine gland hypoplasia. Brachydactyly type E (MIM 113300) presents with shortening of the metacarpals and phalanges in the ulnar ray in association with moderately short stature. We describe a three-generation family with variable expression of ulnar/fibular hypoplasia, brachydactyly, ulnar ray defects and short stature. The proband had ulnar hypoplasia with missing IV-Vth fingers, fibular hypoplasia on the right, bilateral club feet, growth retardation, a hypoplastic mid- face, an ASD and hemangiomas. She had normal mam- mary tissue and normal sweating. The mother had short stature, midfacial hypoplasia, a hypoplastic ulna and hypoplasia of the IVth metacarpal (brachydactyly) on the right without other associated malformations. The maternal grandfather had mild bilateral fibular hypoplasia and midphalangeal brachydactyly of the IV-Vth toes. His sister had mild short stature and shortening of the IVth metacarpal of the left hand. Two-point linkage analysis with microsatellite markers spanning the Ulnar-Mammary locus at 12q24.1 did not confirm linkage. The patients may have a previously undescribed syndrome. Clin Dysmorphol 12:161–165  c 2003 Lippincott Williams & Wilkins. Clinical Dysmorphology 2003, 12:161–165 Keywords: ulnar ray defect, brachydactyly, oligodactyly, ASD, autosomal dominant a University of Pe ´ cs, Medical Faculty, Department of Medical Genetics and Child Development, Pe ´ cs, Hungary, b University of Pe ´cs, MTA-PTE Clinical Genetics Research Group, Pe ´ cs, Hungary and c Tulane University, Department of Psychiatry and Department of Human Genetics, Hayward Genetics Center, New Orleans, LA, USA. Correspondence and request for reprints to Eva Morava MD PhD, Department of Medical Genetics and Child Development, University of Pe ´ cs, Medical Faculty, Pe ´cs, 7623 Jo ´zsef Attila u. 7, Hungary. Tel: + 36 7253 5977;fax: + 36 7253 5972; e-mail: emorava@yahoo.com Received 13 August 2002 Accepted 8 February 2003 Introduction The ulnar mammary syndrome (UMS; MIM 181450) is an autosomal dominant condition with a characteristic face, ulnar and fibular ray defects, oligodactyly, postnatal growth deficiency, abnormal sexual development, nipple hypoplasia and decreased ability to sweat (Gonzales et al., 1976; Schinzel et al., 1987). Several other malformations but no cardiac defects have been associated with the syndrome (Bamshad et al., 1996; Gonzales et al., 1976; Schinzel et al., 1987; Tyler, 1985). Reported families have shown high penetrance with significant intrafamilial variability (Bamshad et al., 1999). Mutations in the gene TBX3 (MIM 601621) mapped to chromosome 12q24.1 have been demonstrated. Mutation in the gene are hypothesized to interfere with limb patterning of the posterior elements of forearm, wrist and hand. The exact mechanism of malformation of the other organs is not yet known (Bamshad et al., 1996; 1999, Killoran et al., 2000). In Holt-Oram syndrome (HOS; MIM 142900) mostly symmetrical radial ray defects are associated with atrial septum defect (ASD), without lower limb malformations and with normal stature. Mutations of the TBX5 gene (MIM 601620) proximal to TBX3 on chromosome 12 have been detected in different families. We report on a patient with an unilateral ulnar ray defect and oligodactyly, a fibular ray defect with bilateral club feet, postnatal growth retardation and an ASD. Her mother had an unilateral ulnar ray defect, brachydactyly, short stature and no other malformations. One maternal family member had short stature and brachydactyly, another had fibular and metacarpal/phalangeal hypoplasia. Clinical report Patient 1 (IV/1) Our proband is the only child of healthy, non-consangui- neous parents (mother was 28, father was 29 years old at birth). The female child was born at term by spontaneous vaginal delivery with a birth weight of 2.7 kg. She was noted to have bilateral club feet. The right leg was 1.5 cm shorter, partial syndactyly of the IV-Vth toes was found. Hypoplasia of the lower segment of the right arm and postaxial oligodactyly (missing IV–Vth fingers) were present (Figure 1A). Her face was round with midface hypoplasia and a prominent forehead (Figure 2A). Hemangiomata of 2 cm in diameter were observed on the forehead and the neck. No pigmentary changes, perspiration abnormality or mammary hypoplasia were present. An echocardiogram revealed an atrial septum 0962-8827  c 2003 Lippincott Williams & Wilkins DOI: 10.1097/01.mcd.0000072164.33788.0a Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.