A CLINICAL AND GENETIC-STUDY OF CAMPOMELIC DYSPLASIA

Campomelic dysplasia (CMD) is a rare skeletal disorder that is usually lethal. It is characterised by bowing of the lower limbs, severe resp iratory distress, and many of the chromosomal (XY) males show sex reve rsal. Because of a number of reports of familial campomelic dysplasia it is considered to be inherited in an autosomal recessive manner. In this study, details of 36 patients with campomelic dysplasia were coll ected from genetic centres, radiologists, and pathologists in the Unit ed Kingdom. The chromosomal sex ratio was approximately 1:1. There was a preponderance of phenotypic females owing to sex reversal. Three qu arters of the chromosomal males were sex reversed or had ambiguous gen italia. Three cases are still alive, two with chromosomal rearrangemen ts involving chromosome 17q. The majority of the others died in the ne onatal period. The 36 index cases had 41 sibs of whom only two were af fected. Formal segregation analysis gave a segregation ratio of 0.05 ( 95% CI similar to 0.00 to 0.11). This excludes an autosomal recessive mode of inheritance. The data suggest a sporadic, autosomal dominant m ode of inheritance. Patients with a chromosomal rearrangement involvin g 17q (q23.3-q25.1) show a milder phenotype. The molecular mechanism f or the difference is still unknown.