ANALYSIS OF VARIABILITY OF CLINICAL MANIFESTATIONS IN WAARDENBURG SYNDROME

Expression of clinical findings of Waardenburg syndrome type 1 (WS1) a nd type 2 (WS2) is extremely variable. Using our collection of 26 WS1 and 8 WS2 families, we analyzed the occurrence, severity, and symmetry of clinical manifestations associated with WS. We found significant d ifferences between WS1 and WS2 in deafness, and in pigmentary and cran iofacial anomalies. Factor analysis was used to identify manifestation s which covaried, resulting in 2 orthogonal factors. Since mean factor scores were found to differ when compared between WS1 and WS2, we sug gest that these factors could be useful in distinguishing WS types. We found that the WS gene was transmitted from mothers more often than f rom fathers. We also extensively examined the W-Index, a continuous me asure of dystopia canthorum. Our data suggest that use of the W-Index to discriminate between affected WS1 and WS2 individuals may be proble matic since 1) ranges of W-Index scores of affected and unaffected ind ividuals overlapped considerably within both WS1 and WS2, and 2) a con siderable number of both affected and unaffected WS2 individuals exhib ited W-index scores consistent with dystopia canthorum. Misclassificat ion of families may have implications for risk assessment of deafness, since WS2 families have been reported to have greater incidence of de afness, as confirmed in our study. (C) 1995 Wiley-Liss, Inc.