CEPHALOMETRIC ANALYSIS OF FAMILIES WITH DOMINANTLY INHERITED CROUZON-SYNDROME - AN AID TO DIAGNOSIS IN FAMILY STUDIES

Crouzon syndrome (CS) is an autosomal dominant condition comprising or bital proptosis, midfacial hypoplasia, premature sutural synostosis, a nd altered proportions of bone lengths in the hands. In families the C S trait is highly variable. Several cases of affected sibs born to una ffected parents have been explained by germinal mosaicism. We hypothes ized that cephalometric and metacarpophalangeal analysis may help to c lassify affected and unaffected subjects within families when clinical diagnosis is difficult. Posterior-anterior and lateral cephalometric radiographs and hand films were taken of 10 CS patients and 18 unaffec ted relatives. Sixty-two craniofacial and 19 hand linear and angular m easurements were made on each subject and standardized by conversion t o z-scores using published normal standards. Ten craniofacial variable s were selected for use in a stepwise forward discriminant function an alysis to develop an equation which could be used to discriminate CS p atients from normal subjects. A two-group discriminant function using four craniofacial variables and one hand variable correctly classified the CS patients and relatives 100 % of the time. The results suggest that relatively few facial variables are needed to differentiate most cases of CS but the addition of one or more hand variables may increas e the sensitivity. DNA testing is necessary to adequately demonstrate incomplete penetrance in CS, but pretesting subjects for molecular stu dies using these methods may improve results. (C) 1998 Wiley-Liss, Inc .