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 …