Investigators Discover Mutations in KMT2B Cause Complex Childhood Dystonia


Despite great advances in dystonia genetics, the underlying genetic causes for most cases of childhood onset dystonia remain unknown. However, a team led by researchers from University College London published a seminal paper describing their discovery of mutations in a gene called KMT2B that cause progressive childhood dystonia. The investigators describe KMT2B dystonia as a dominantly inherited, complex dystonia with onset in infancy or early childhood. Most patients develop dystonia in the limbs as well as pronounced cervical, cranial and laryngeal involvement. Some of the children presented with intellectual disability, psychiatric disorders, specific facial characteristics, and other non-motor symptoms.

The KMT2B protein belongs to a class of proteins that control transcription of other genes and that have been implicated in other neurological conditions. In addition to identifying a novel genetic movement disorder, the team discovered a potentially pivotal mechanism causing dystonia through the so called epigenetic modification. Moreover, it has been observed that although this particular dystonia does not respond well to treatment with oral medications, it can effectively be treated with deep brain stimulation (DBS). The children’s response to DBS was profound, in some cases, restoring the ability to walk.  

This work demonstrates yet again that proper diagnosis, including comprehensive genetic testing, is necessary to achieve the most effective therapeutic treatment.

Zech M, Boesch S, Maier EM, et al. Haploinsufficiency of KMT2B, Encoding the Lysine-Specific Histone Methyltransferase 2B, Results in Early-Onset Generalized Dystonia. Am J Hum Genet. 2016 Dec 1;99(6):1377-1387.

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