Kleefstra syndrome is a rare disorder characterized by moderate to severe intellectual disability, childhood hypotonia, developmental delay and extremely limited speech capabilities. Patients often suffer from distinctive facial dysmorphia, such as brachycephaly, microcephaly, flat face, mid face hypoplasia, hypertelorism, synophrys, a full everted lower lip, a protruding tongue and prognathism. Some patients may also exhibit behavioral problems such as obsessive-compulsive disorder, stereotypic movements and aggressive behavior. Other symptoms may include sleep issues, obesity, brachydactyly and cardiovascular anomalies such as conotruncal heart defects.
Kleefstra syndrome is a rare condition with about 200 affected individuals reported worldwide. Due to its recent discovery and the limited number of cases, the prognosis of the disorder is not completely known. The condition affects men and women equally and does not appear to have a racial or ethnic bias.
The diagnosis can be confirmed by molecular testing of the EHMT1 gene. While there is currently no cure for the disorder, affected individuals benefit from early intervention strategies, including physical and occupational therapy, speech therapy and behavioral therapy. Patients may require medication for sleep issues, behavioral problems and to treat epilepsy.
Monies et al. (2017) investigated the findings of 1000 diagnostic panels and exomes carried out at a next generation sequencing lab in Saudi Arabia. One male patient from a consanguineous family presented with speech and mental delay, learning disability, recurrent fever, seizures and GTC epilepsy. Using whole exome sequencing a heterozygous mutation (c.6589C>A, p.Q2197K) was identified in exon 36 of the patient’s KMT2C gene. A mutation in the KMT2C gene had previously been tentatively linked to Kleefstra syndrome, and hence this result was seen to confirm this association.