AUTOSOMAL-DOMINANT TETRAMELIC POSTAXIAL OLIGODACTYLY

Postaxial limb deficiencies are most frequently unilateral and sporadi c with deficiencies of the ulnar ray about one-third as common as thos e affecting the radial ray. Postaxial deficiency occurs in a number of genetic and sporadic syndromes, but isolated inherited tetramelic, po staxial oligodactyly has to our knowledge not been described. We repor t an affected mother and her 3 affected children from a 4-generation f amily with apparent autosomal dominant, non-syndromic, tetramelic, pos taxial oligodactyly. The affected individuals manifest a very uniform pattern of postaxial deficiency ranging from complete absence of the 5 th metacarpals, metatarsals, and phalanges to complete absence of the 5th metacarpals and metatarsals, but with some residual distal 5th pha langes. Limb buds may be considered a single developmental field with development proceeding rostral to caudal. Digit formation is apparentl y controlled by the zone of polarizing activity which releases a diffu sible morphogen specifying positional information along the anterior/p osterior axis. Recent investigations using chick and mouse embryo mode ls suggest that 5' members of the Hox-4 gene cluster are responsible f or interpreting this positional information to effect digit formation. The present family may represent a defect in Hox-4 gene patterning of hand and foot formation, an abnormality in morphogen gradient formati on or alternately an inability of the most ulnar rays to respond to mo rphogen (receptor defect).