EPM CSNK1E

Progressive myoclonic epilepsy is a heterogeneous neurodegenerative disorder characterized by early-onset myoclonus, epilepsy, generalized tonic-clonic seizures, and progressive neurological deterioration. It has also been proposed that this locus is also associated with developmental and epileptic encephalopathies. We hypothesize that the two diseases may make up an expressivity or phenotypic spectrum and/or that hypermethylation causes changes in onset and severity.

Prevalence

EPM found in one Azerbaijani probandand DEE found in two additional patients. This expansion has been reported in unaffected individuals.

Age of Onset Details

EPM case reports age of onset 10 yearsand DEE cases onset in infancy

Locus

hg19

chr22:38713287-38713380

hg38

chr22:38317282-38317375

t2t

chr22:38781587-38781680

Details

CGG repeat in exon 1 of CSNK1E. Longest reported expanded allele of an affected individual is 745, with an unaffected sibling with repeat length 980. Father had a repeat of 8 and mother of 131.

Mechanism

Unknown

Mechanism of this disease is largely unknown, but hypermethylation is observed. Expanded alleles exhibit hypermethylation and may mediate epigenetic silencing. Unaffected carriers have been observed, indicating variable expressivity or penetrance.

Year

2025

Location in Gene

Exon 1

Gene Strand

Alleles

Ref. Motif

CCG

Pathogenic (ref.)

CCG

Pathogenic (gene)

CGG