Kleefstra syndrome

Kleefstra syndrome, also known as 9q34 deletion syndrome, is a rare genetic disorder. Terminal deletions of chromosome 9q34 have been associated with childhood hypotonia, distinctive facial appearance and intellectual disability. Most individuals fall within the moderate to severe range of intellectual disability, while a minority shows mild delays and have total IQ scores within the low-normal range. Typical facial features include arched eyebrows, microcephaly, midface hypoplasia, a prominent jaw and a pouting lower lip. Affected individuals often exhibit speech impairments, including significant speech delays. Severe expressive language delays with limited speech production are common; however, general language development is often more advanced, enabling non-verbal communication. Other common features include epilepsy, congenital and urogenital anomalies, microcephaly, obesity, and psychiatric disorders. Through analysis of chromosomal breakpoints, as well as gene sequencing in suggestive cases, Kleefstra and colleagues identified EHMT1 as the causative gene: this gene is responsible for producing the protein histone methyltransferase whose function is to alter histones. Histone methyltransferases are also important in deactivating certain genes needed for proper growth and development. Moreover, a frameshift, missense, or nonsense error in the coding sequence of EHMT1 can result in this condition in an individual.