Onset of symptoms is normally within the first year of life with truncal ataxia and seizures. The head is small (microcephaly). Common facial abnormalities include: [citation needed]
This condition is caused by mutations in the SLC9A6 gene. This gene is located on the long arm of the X chromosome (Xq26.3). The gene encodes a sodium/hydrogen exchanger located in the endosomes. Mutations in this gene cause a decrease in the pH (overacidification) of the endosomes.[1][2]
How this causes the clinical features is not known presently. The inheritance of this condition is X-linked dominant.
^Christianson AL, Stevenson RE, van der Meyden CH, Pelser J, Theron FW, van Rensburg PL, Chandler M, Schwartz CE (1999) X linked severe mental retardation, craniofacial dysmorphology, epilepsy, ophthalmoplegia, and cerebellar atrophy in a large South African kindred is localised to Xq24-q27. J Med Genet 36:759–766
^Gilfillan GD, Selmer KK, Roxrud I, Smith R, Kyllerman M, Eiklid K, Kroken M, Mattingsdal M, Egeland T, Stenmark H, Sjøholm H, Server A, Samuelsson L, Christianson A, Tarpey P, Whibley A, Stratton MR, Futreal PA, Teague J, Edkins S, Gecz J, Turner G, Raymond FL, Schwartz C, Stevenson RE, Undlien DE, Strømme P (2008) SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome. Am J Hum Genet 82:1003–10
