X-linked oligophrenic vermian dysgenesis

X-linked mental retardation (XLMR) has often been divided into syndromic XLMR (S-XLMR) vs non-syndromic XLMR (NS-XLMR) based on the presence or absence of somatic and dysmorphic features. Although mental retardation by definition is the only clinical feature of NS-XLMR, the concept of NS-XLMR as a nosologic entity is losing its identity as new candidate genes for XLMR are discovered. For example, NS-XLMR is caused by mutations in the ARX gene but other mutations within the ARX gene cause additional features: ambiguous genitalia, lissencephaly, infantile spasms, and agenesis of the corpus callosum.1–3 In fragile X syndrome, a frequent cause of S-XLMR, the typical dysmorphic features of the syndrome may not evolve until late childhood or adolescence.4 These broad phenotypes decrease diagnostic certainty and advocate the screening of selected candidate genes for mutations in individuals with NS-XLMR who do not have cytogenetic abnormalities or CGG trinucleotide repeat expansions in the FMR1 gene (Fragile X syndrome). A panel of candidate genes ( ARX , DLG3 , FACL4 , FTSJ1 , JARID1C , PQBP1 , TM4SF2 , and ZNF41 ) has a mutation detection rate up to 20% to 25% of individuals with NS-XLMR. New testing strategies are on the horizon as the functional aspects of these genes are characterized and newer DNA and protein …