Kleefstra syndrome (KS), previously known as the 9q subtelomeric deletion syndrome (9qSTDS) is caused by haploinsufficiency of the EHMT1 gene. Both a single mutation and 9q34 microdeletions encompassing the entire gene can be responsible for this syndrome which is characterized by intellectual disability, hypotonia, and typical dysmorphisms, and may be associated with congenital heart and/or renal defects and epilepsy. Its behavioral phenotype has recently been described and comprises particular sleep disturbances and apathy. In this report, the evolution of the behavioral profile of KS is outlined by the description of three female patients aged 19, 33, and 43 years, respectively. In two patients, the syndrome was caused by an intragenic mutation and in the third by a 9q34 microdeletion encompassing the EHMT1 gene. MRI scanning of the brain in the two eldest patients demonstrated multifocal subcortical signal abnormalities. In general, the severity of the behavioral and motor deficiencies increased over time and became apparent after adolescence. It is concluded that the "regressive" phenotype of KS seems to be associated with the EHMT1 gene in particular. In addition, the utility of uncritical use of a classificatory diagnostic approach is discussed in the context of the motor and motivational disturbances that are prominent in this syndrome.

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doi.org/10.1002/ajmg.a.34186, hdl.handle.net/1765/30862
American Journal of Medical Genetics. Part A
Erasmus MC: University Medical Center Rotterdam

Verhoeven, W., Egger, J., Vermeulen, K., van de Warrenburg, B., & Kleefstra, T. (2011). Kleefstra syndrome in three adult patients. American Journal of Medical Genetics. Part A, 155(10), 2409–2415. doi:10.1002/ajmg.a.34186