Syndrome of the month Cleft hand / foot : clinical and developmental aspects

Isolated limb reduction defects occur in approximately 1 in 2000 live births within which central ray anomalies are an important subgroup. Most affected persons have mild or moderate functional impairment. Considerable psychological morbidity may also occur. While there have been major strides forwards in our understanding of vertebrate limb development, the mechanisms responsible for central ray deformities remain poorly understood. Several case reports ofcentral clefting anomalies associated with chromosomal rearrangements or interstitial deletions of 7q21.2-q21.3 suggest that this chromosomal region is important for limb development. (J Med Genet 1994;31:726-730) While the term ectrodactyly literally means "missing digits", it is now used as a descriptive term for a central ray anomaly that presents clinically as a central cleft of the hands or feet.' Historically, terms such as "lobster claw"2 and split hand3 have been used to describe this defect which results from absence, or reduction, of one or more of the three central digits (fig 1). The earliest known description of cleft hand was that by Pare4 although Barsky5 suggested that this report represented two fingered hemimelia rather than true cleft hand. Central ray defects, according to Swanson's modified classification, represent terminal longitudinal limb anomalies.6 Cleft limb has a number of associations and as a result it can be Department of Neonatal Medicine, University of Bristol, Bristol BS2 8EG, UK P W Buss Correspondence to Dr Buss, Department of Paediatrics, Royal Gwent Hospital, Newport, Gwent NP9 2UB, UK. a useful major feature for syndrome diagnosis. Large families with isolated cleft limbs have been described which usually show autosomal dominant inheritance and marked variability in expression and penetrance, although several autosomal recessive pedigrees have also been reported.8'0 Birch-Jensen" estimated the incidence of cleft hand deformity at 1 in 90 000 births. More recent epidemiological studies suggest the incidence of central ray anomalies to be closer to 1 in 10 000 (approximately 0.7 per 10 000 live births).'2 '3 The data of Czeizel et all4 indicate that three-quarters (77%) of cases present with unimelic involvement. In 1960 Stevenson and Jennings'5 suggested an abnormal segregation pattern in families with isolated ectrodactyly (pedigree analysis showed an excess of affected sons of affected fathers). David,'6 when describing three pedigrees with isolated cleft limbs, suggested the possibility of germinal mosaicism. X linked inheritance has also been described in a seven generation Pakistani kindred.'7 Ford'8 hypothesised that "ectrodactyly" represented an anomaly that could be explained by a structural chromosomal defect although at that time it was acknowledged that techniques for chromosome analysis were poor. Since then a number of case reports have indicated that the 7q21.2-q21.3 region is a candidate site for cleft limbs. 19-26 These have resulted in considerable molecular interest in this region. Clinical features Clinical problems associated with isolated cleft hand and foot are usually cosmetic and psy-