The effects of the COL4A5 genotype on age at ESRD are not clear in females with XLAS, likely due to the random process of X inactivation (Lyonization) that explains why heterozygous females typically have a variable and generally less severe expression of X-linked recessive disorder than male relatives [27]. This evidence concerns the gene COL4A5 and X-linked hydrocephalus with stenosis of the aqueduct of Sylvius.