American Journal of Medical Genetics 124A:407–410 (2004) Clinical Report A Family With X-Linked Recessive Fusion of Metacarpals IV and V Fortunato Lonardo, 1 Matteo Della Monica, 1 Giovanni Riccardi, 2 Ilaria Riccio, 2 Vincenzo Riccio, 2 and Gioacchino Scarano 1 * 1 Division of Medical Genetics, Gaetano Rummo Hospital, Benevento, Italy 2 Department of Paediatric Orthopaedics, 2nd University of Naples, Naples, Italy We describe a family with a distinctive malformation of the hand consisting of the fusion of the 4th and the 5th metacarpal bones. Usually this anomaly is clinically recognizable by an ulnar deviation of the 5th finger; moreover, the 5th metacarpal is usually hypoplastic and the 5th ray is con- sequently short. There is, however, great variability in expression, so the degree of fusion may range from minimal to complete and also the external aspect of the hand may vary. This anomaly can be either isolated or part of a syndrome. For the isolated form, two possible hereditary mechanisms have been proposed: autosomal dominant and X- linked recessive. Our family is consistent with the latter, with only affected males and no instances of male-to-male transmission. Of note, there are very few X-linked recessive disorders that affect the hand in a such a specific way. ß 2003 Wiley-Liss, Inc. KEY WORDS: metacarpal 4–5 fusion; metacarpal synostosis; hand malformation; X-linked inheritance INTRODUCTION Metacarpal synostosis is a rare malformation, clini- cally variable, and causally heterogeneous [Miura, 1988; Buck-Gramcko and Wood, 1993; Ogino and Kato, 1993]. It usually affects the 4th and the 5th metacarpal bones, and can be observed as an isolated anomaly in otherwise normal individuals or associated with other malformations. In a few families, the fusion between IV and V metacarpals has been described as an inherited trait. Lerch [1948] and Habighorst and Albers [1965] sug- gested an autosomal dominant inheritance because of affected females and male-to-male transmission. Four other pedigrees, in which only males were affected with no instances of male-to-male transmission, were con- sistent with X-linked recessive inheritance [Orel, 1928; Holmes et al., 1972; Hooper and Lamb, 1983; Anneren and Amilon, 1994]. Holmes et al. [1972] raised the possibility of a kinship between the family they reported and a Russian child reported earlier by Shiryak [1961] as an isolated case. We report another family with five males affected in three generations, consistent with X-linked inheritance. CLINICAL REPORT Our propositus is the first child of healthy, non- consanguineous parents. He was born at term after an uneventful gestation with a weight of 3,250 g. At the age of 4 years, he underwent surgical correction of a right- sided inguinal hernia. When he was 15 years old, the parents noted some problem in his spine. An orthopedic evaluation ascertained a thoracolumbar scoliosis and noted also a short 5th ray in both hands. Radiographs of spine and hands confirmed the scoliosis from T6 to L2 (308) and showed a fusion between IV and V metacar- pals, with brachyphalangia of the 5th ray. When referred to us, at 15 9/12 years, he had a Marfanoid habitus. His height was 178.5 cm (75th – 90th centile), the span was 187.5 cm, the left hand measured 20.5 cm (75th–97th centile), the palm 11.5 cm (75th– 97th centile), the middle finger 9 cm (>97th centile), with a middle finger/total ratio of 0.44 (75th centile). He had a brachycephalic skull with mild bitemporal constriction and micro/retrognathia. The thoraco-lum- bar scoliosis and the bilaterally shortened 5th ray of the hands were also evident. The metacarpo-phalangeal profile (Fig. 1) was irregular because of a progressive *Correspondence to: Dr. Gioacchino Scarano, M.D., A.O.R.N. Gaetano Rummo, Unita ` Operativa Complessa di Genetica Medica, Via dell’Angelo, 1, I-82100 Benevento (BN), Italy. E-mail: gioacchino.scarano@ao-rummo.it Received 13 March 2003; Accepted 6 May 2003 DOI 10.1002/ajmg.a.20382 ß 2003 Wiley-Liss, Inc.