X-linked hydrocephalus (HSAS) (MIM *307000),
MASA syndrome (MIM *303350), and complicated
spastic paraplegia (
SPG1) (MIM *312900) are closely related. Soon after delineation,
SPG1 was incorporated into the spectrum of
MASA syndrome. HSAS and
MASA syndrome show great clinical overlap;
DNA linkage analysis places the loci at Xq28. In an increasing number of families with
MASA syndrome or HSAS, mutations in
L1CAM, a gene located at Xq28, have been reported. In order to further delineate the clinical spectrum, we studied 6 families with male patients presenting with
MASA syndrome, HSAS, or a mixed phenotype. We summarized data from previous reports and compared them with our data. Clinical variability appears to be great, even within families. Problems in genetic counseling and prenatal diagnosis, the possible overlap with
X-linked corpus callosum agenesis and
FG syndrome, and the different forms of X-linked complicated
spastic paraplegia are discussed. Since adducted thumbs and
spastic paraplegia are found in 90% of the patients, the condition may be present in males with nonspecific
mental retardation. We propose to abandon the designation
MASA syndrome and use the term HSAS/
MASA spectrum, incorporating
SPG1.