Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar;65(3):709-724.
doi: 10.1111/epi.17880. Epub 2024 Jan 17.

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

Sangeetha Yoganathan  1 , Robyn Whitney  2 , Maya Thomas  1 , Sumita Danda  3 , Akbar Mohamed Chettali  4 , Asuri N Prasad  5 , Sali M K Farhan  6 , Daad AlSowat  7 , Musaad Abukhaled  7 , Hesham Aldhalaan  7 , Vykuntaraju K Gowda  8 , Uddhava V Kinhal  8 , Arun Y Bylappa  8 , Ramesh Konanki  9 , Lokesh Lingappa  9 , Bindu Madhavi Parchuri  10 , Juan P Appendino  11 , Morris H Scantlebury  12 , Jessie Cunningham  13 , Aristides Hadjinicolaou  14 , Christelle Moufawad El Achkar  15 , Mahesh Kamate  16 , Ramshekhar N Menon  17 , Manna Jose  17 , Gillian Riordan  18 , Lakshminarayanan Kannan  19 , Vivek Jain  20 , Ranjith Kumar Manokaran  21 , Vann Chau  22 , Elizabeth J Donner  23 , Gregory Costain  24 , Berge A Minassian  25 , Puneet Jain  23
Affiliations

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

Sangeetha Yoganathan et al. Epilepsia. 2024 Mar.

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.

PubMed Disclaimer

References

REFERENCES

    1. Minassian BA. The progressive myoclonus epilepsies. Prog Brain Res. 2014;213:113-122.
    1. Shahwan A, Farrell M, Delanty N. Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects. Lancet Neurol. 2005;4(4):239-248.
    1. Berkovic SF, Dibbens LM, Oshlack A, Silver JD, Katerelos M, Vears DF, et al. Array-based gene discovery with three unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis. Am J Hum Genet. 2008;82(3):673-684.
    1. De Souza Crippa AC, Franklin GL, Takeshita BT, Ghizoni Teive HA. DNM1L mutation presenting as progressive myoclonic epilepsy associated with acute febrile infection-related epilepsy syndrome. Epileptic Disord. 2022;24(5):976-978.
    1. Bassuk AG, Wallace RH, Buhr A, Buller AR, Afawi Z, Shimojo M, et al. A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome. Am J Hum Genet. 2008;83(5):572-581.

Publication types

LinkOut - more resources