%0 Systematic Review
%T KCTD7-related progressive myoclonic epilepsy: Report of 42 cases and review of literature.
%A Yoganathan S
%A Whitney R
%A Thomas M
%A Danda S
%A Chettali AM
%A Prasad AN
%A Farhan SMK
%A AlSowat D
%A Abukhaled M
%A Aldhalaan H
%A Gowda VK
%A Kinhal UV
%A Bylappa AY
%A Konanki R
%A Lingappa L
%A Parchuri BM
%A Appendino JP
%A Scantlebury MH
%A Cunningham J
%A Hadjinicolaou A
%A El Achkar CM
%A Kamate M
%A Menon RN
%A Jose M
%A Riordan G
%A Kannan L
%A Jain V
%A Manokaran RK
%A Chau V
%A Donner EJ
%A Costain G
%A Minassian BA
%A Jain P
%J Epilepsia
%V 65
%N 3
%D 2024 Mar 17
%M 38231304
%F 6.74
%R 10.1111/epi.17880
%X 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).
CONCLUSIONS: 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.