Metacarpophalangeal analysis in Crouzon syndrome: Additional evidence for phenotypic convergence with the acrocephalosyndactyly syndromes

Abstract

Crouzon syndrome (CS) is characterized by premature craniosynostosis, orbital proptosis, and midfacial hypoplasia and is related to the acrocephalosyndactylies (ACS) with limb abnormalities. In CS the hands are considered to be normal, but a previous report indicated that there is consistent alteration in the proportions of the bones of the hands, as shown by metacarpophalangeal analysis (MCPP), in at least some cases of CS. The purpose of this study was to extend these findings by examining affected individuals and their supposedly unaffected first degree relatives. If CS does have an effect on hands, then this should only be evident in the affected individuals and, presuming complete penetrance, not present in their unaffected relatives. PA hand films were taken on 12 CS subjects and 16 of their normal relatives. The lengths of the metacarpals and phalanges were measured and the measurements standardized for age and sex by conversion to z-scores using published normal standards. Mean pattern profiles for the 2 groups were plotted. In CS the phalanges, especially the first and second proximal phalanges and the first distal phalanx, were shorter than average, and shorter than those of unaffected relatives. The metacarpals were not significantly smaller than the reference means in CS. The 19 hand measurements were entered into a stepwise forward discriminant function analysis (DFA) to develop a model that would discriminate between CS subjects and their normal first degree relatives. The function generated used the measurements of 8 hand bones to classify correctly CS subjects and their normal relatives 100% of the time. This study confirmed that there is a radiographically detectable abnormality of the hands in CS and that, at least in this sample, relatives did not display such abnormalities. Therefore, it seems that CS shares postcranial effects with true ACS and that these effects are, like the other aspects of CS, fully penetrant.