Limb anomalies in chromosomal aberrations

This survey shows that there are at least 6 autosomal and 2 gonosomal aberrations which may produce specific types of limb anomaly in 30%-80% of cases. The "expressivity" of these anomalies covers a wide range within the morphogenetic pattern. No entirely specific malformation type is seen. The most unusual malformation, aplasia of the thumbs with proximal synostosis of the 4th aand 5th metacarpals, is seen in 13q- (13r) but the precise cytogenetic basis is not clear. Aplasia of the thumb associated with synostosis of the 4th and 5th metacarpals was occasionally described before (unilateral [105], bilateral [106] while synostosis only (V or Y shaped) may be due to a dominant [107] or an X-linked recessive gene [108]. Reduction malformations limited to radial heminelia have been noted in 4q- (4r) and in trisomy 18. Although the number of cases is still small the pattern is similar to that of thalidomide embryopathy, radial hemimelia (AD, 17910), cardiodigital syndromes (AD, 14290), and even Fanconi panmyelopathy (AR, 22790). It ranges from hypoplasia of the thenar muscles and thumb to pseudophocomelia which should be clearly distinguished from phocomelia because of the absence of the thumb and frequently of the 2nd and 3rd fingers. Nothing has to be added to the teratologic series published by Müller [58] and, more recently, Willert and Henkel [109], but the distribution of the various manifestations may diverge. Asymmetry in 4q- (4r) is noteworthy. Postaxial polydactyly which is noted in trisomy 13 and trisomy of the terminal portions of the long arm of No. 13 is as variable in distribution and morphology as is observed in families in which the gene (AD, 17420) is transmitted. The question cannot yet be answered whether infrequent anomalies of the limbs which do not fit into the morphologic pattern of these types, eg postaxial polydactyly in + 18 or absence of the radius in + 13 are random. Syndactyly of the 3rd and 4th but also of other digits is a frequent but variable anomaly in triploidy. It is very similar to hereditary zygodactyly (AD, 18590). Peripheral hypoplasia of several digits accompanied by onychodysplasia seems to be a frequent anomaly in 9p+ syndrome. It is similar to that seen in a syndrome with mental deficiency, peculiar facies, and stunted growth [110] in which no chromosomal aberration has been found up to the present. Dysostoses have been frequently noted in gonosomal aberations. Brachymetopodia in XO females maybe confused with pseudo-pseudohypoparathyroidism (XR, 30080) or brachydactyly type E (AD, 11330) when only the lateral metacarpals and/or metatarsals are shortened. However, further studies are needed in order to delineate these syndromes on the basis of different frequencies and radiologic patterns. The radioulnar synostosis noted in cases with supernumerary X chromosomes cannot be distinguished from the inherited anomaly (AD, 17930), but associated anomalies of the hand are uncommon.