9q34.3 deletion syndrome
| 9q34.3 deletion syndrome | |
|---|---|
| Other names | Kleefstra syndrome |
| This photo shows person with Kleefstra syndrome, with unibrow, relative mandibular prognathism, a short nose with wide base, hypertelorism with epicanthus. Although, not shown in the picture, this person also has overfolded ears that are posteriorly angulated with a deep notch on the left ear lobe. | |
| Specialty | Medical genetics |
| Symptoms | Arched eyebrows, small head circumference, midface hypoplasia, prominent jaw and a pouting lower lip. |
| Causes | Genetics. |
| Diagnostic method | Fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, array comparative genomic hybridization, and EHMT1 sequencing. |
| Differential diagnosis | Down syndrome, Smith-Magenis syndrome, Pitt-Hopkins syndrome, Angelman syndrome, and MBD5 haploinsufficiency. |
| Named after | Tjitske Kleefstra |
9q34 deletion syndrome, now known as Kleefstra 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.