KCTD7 was first reported in relation to autosomal recessive progressive myoclonus epilepsy (PME) in 2007 (Van Bogaert et al., PMID: 17455289). The typical clinical presentation is characterized by onset of myoclonic seizures in infancy or early childhood followed by developmental regression and ataxia, sometimes also associated with cerebral or cerebellar atrophy and microcephaly (PMID: 34866617). Up to 25% of individuals with KCTD7 pathogenic variants have developmental delay and/or movement disorders such as ataxia, dyskinesia, dystonia, choreoathetosis, or tremors prior to the onset of seizures (PMIDs: 30295347, 31197948).
The mechanism of pathogenicity is known to be loss of function (LOF). To date, approximately 55 missense, nonsense, frameshift, and splicing variants have been reported in more than 50 probands in the literature. Eight publications (PMIDs: 17455289, 22638565, 22693283, 27742667, 30295347, 30825425, 22748208, 25060828) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. This gene-disease association is also supported by experimental evidence from an animal model that exhibits spontaneous seizure activity in a knockout mouse (PMIDs: 35972048).
In summary, KCTD7 is definitively associated with autosomal recessive progressive myoclonus epilepsy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time.
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