Kleefstra-variant syndrome with heterozygous mutations in EHMT1 and KCNQ2 genes: a case report

We report the results of genetic analysis by whole exome sequencing (WES) of an atypical case of Kleefstra syndrome (KS), with psychomotor delay and intellectual disability, muscle hypotonia and dysmorphic traits accompanied by clonic seizures beginning very early after birth. KS (OMIM #610253) is a genetic disorder characterized clinically by the phenotypical features of intellectual disability, severely limited or absent speech, hypotonia, synophrys, hypertelorism and microcephaly. In approximately 75% of cases, KS is caused by heterozygous microdeletions in 9q34.3 or de novo point mutations in euchromatin histone methyltransferase 1 (EHMT1) gene, and point mutations in EHMT1 can cause also severe intellectual disability and behavioral disorders. This is the first report describing a proband affected by KS carrying a deleterious mutation in KCNQ2, in addition to one in EHMT1, and its results support the notion that WES can be useful to investigate the mechanisms underlying atypical clinical manifestations of monogenetic diseases