Whereas syndromic hydrocephalus has been associated with more than 100 disease-causing genes, only four genes are currently known to be linked to congenital hydrocephalus as isolated or as the major clinical feature: L1CAM, AP1S2, MPDZ and CCDC88C. Pathogenic L1CAM variants are responsible for a wide phenotypic spectrum, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (AS) being the most common genetic form, with a prevalence of 1:30,000 and accounting for approximately 5–10% of males with non-syndromic congenital hydrocephalus. The gene discussed is MPDZ; the disease is congenital hydrocephalus.