Rhythmic cortical myoclonus in patients with 6Q22.1 deletion

DNA deletions involving 6q22.1 region result in developmental encephalopathy (DE), often associated with movement disorders and epilepsy. The phenotype is attributed to the loss of the NUS1 gene included in the deleted region. Here we report three patients with 6q22.1 deletions of variable length all showing developmental delay, and rhythmic cortical myoclonus. Two patients had generalized seizures beginning in infancy. Myoclonic jerks had polygraphic features consistent with a cortical origin, also supported by cortico-muscular coherence analysis displaying a significant peak around 20 Hz contralateral to activated segment. Deletions in 6q22.1 region, similarly to NUS1 loss-of-function mutations, give rise to DE and cortical myoclonus via a haploinsufficiency mechanism. A phenotype of progressive myoclonic epilepsy (PME) may also occur.