GENETIC-HETEROGENEITY IN X-LINKED HYDROCEPHALUS - LINKAGE TO MARKERS WITHIN XQ27.3

X-linked hydrocephalus is a well-defined disorder which accounts for g reater than or equal to 7% of hydrocephalus in males. Pathologically, the condition is characterized by stenosis or obliteration of the aque duct of Sylvius. Previous genetic linkage studies have suggested the l ikelihood of genetic homogeneity for this condition, with close linkag e to the DXS52 and F8C markers in Xq28. We have investigated a family with typical X-linked aqueductal stenosis, in which no linkage to thes e markers was present. In this family, close linkage was established t o the DXS548 and FRAXA loci in Xq27.3. Our findings demonstrate that X -linked aqueductal stenosis may result from mutations at two different loci on the X chromosome. Caution is indicated in using linkage for t he prenatal diagnosis of X-linked hydrocephalus.