In the last 3 years de novo sequence variants in the ARID2 (AT-rich interaction domain 2) gene, a subunit of the SWI/SNF complex, have been linked to intellectual disabilities in 3 case reports including one which describes frameshift mutations in ARID2 in 2 patients with features resembling Coffin-Siris syndrome.
X-linked α-thalassemia with mental retardation (ATRX) is a chromatin remodeling protein that belongs to the SWItch/sucrose non-fermentable (SWI2/SNF2) family of helicase/ATPases.
Genes encoding epigenetic regulators are a frequent cause of intellectual disability and many have been shown to regulate progenitor cell growth, including our inactivation of the <i>Smarca1</i> gene encoding Snf2l, which is one of two <i>ISWI</i> mammalian orthologs.
Beyond neoplasms, several congenital developmental functional disorders such as Coffin-Siris syndrome and intellectual disability are now known to be SWI/SNF-related.
However, our patient showed overlapping features with Nicolaides-Baraitser syndrome and Coffin-Siris syndrome, providing further arguments to reclassify these disorders as "SWI/SNF-related intellectual disability syndromes."