KCTD7-related progressive myoclonic epilepsy: Report of 42 cases and review of literature

Epilepsia. 2024 Mar;65(3):709-724. doi: 10.1111/epi.17880. Epub 2024 Jan 17.

Abstract

Objective: KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a large international cohort.

Methods: Families with molecularly confirmed diagnoses of KCTD7-related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging-related variables were collected and summarized.

Results: Forty-two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75-22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty-one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5-21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7-related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3-18 years).

Significance: This study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7-related disorders. Early onset drug-resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials.

Keywords: CLN14; epileptic encephalopathy; neurodegenerative; neuronal ceroid lipofuscinosis; opsoclonus; progressive myoclonic epilepsy.

Publication types

  • Systematic Review

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Electroencephalography
  • Epilepsies, Myoclonic* / genetics
  • Humans
  • Infant
  • Myoclonic Epilepsies, Progressive* / genetics
  • Potassium Channels / genetics
  • Seizures
  • Unverricht-Lundborg Syndrome*
  • Young Adult

Substances

  • KCTD7 protein, human
  • Potassium Channels