HETEROGENEITY IN SCHWARTZ-JAMPEL CHONDRODYSTROPHIC MYOTONIA

The Schwartz-Jampel syndrome (SJS; chondrodystrophic myotonia; McK 255 800) is a recessively inherited condition defined by myotonia, short s tature, and bone dysplasia. Genetic linkage between SJS and chromosoma l region 1q36-34 has been observed in several families, but the gene h as not yet been identified. We studied the clinical and radiological f eatures in 81 patients from the literature and 5 own patients trying t o identify distinct subgroups. In addition, we tested genetic linkage to the SJS locus on chromosome 1 in one family with two affected sibs. We found that a group of patients have mild skeletal changes which ma y be secondary consequences of myotonia, while another group of patien ts appear to have primary bone dysplasia with myotonia. Within this la tter group, there are differences in age of manifestation, clinical co urse and pattern of bone changes. We tentatively isolate three differe nt types of SJS: type 1A, usually recognized in childhood, with modera te bone dysplasia, corresponding to the original descriptions of Schwa rtz, Jampel and Aberfeld; type 1B, similar to type 1A but recognizable at birth, with more pronounced bone dysplasia resembling Kniest dyspl asia; and type 2, manifest at birth, with increased mortality and bone dysplasia resembling Pyle disease. Genetic analysis of the family wit h two sibs affected by SJS type 2 showed evidence against linkage to c hromosome lp36-34. Conclusions SJS is clinically and radiologically he terogeneous. The causes of heterogeneity are not known yet but are lik ely to include both different mutations at the SJS locus on chromosome 1 and the presence of a second SJS locus. A tentative clinicoradiolog ical classification can be useful for the characterization of patients and the development of genotype-phenotype correlations.