KCTD7-related progressive myoclonic epilepsy: Report of 42 cases and review of literature.
CLN14
epileptic encephalopathy
neurodegenerative
neuronal ceroid lipofuscinosis
opsoclonus
progressive myoclonic epilepsy
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
revised:
02
01
2024
received:
14
07
2023
accepted:
03
01
2024
pubmed:
17
1
2024
medline:
17
1
2024
entrez:
17
1
2024
Statut:
ppublish
Résumé
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. 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. 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). 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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
709-724Informations de copyright
© 2024 International League Against Epilepsy.
Références
Minassian BA. The progressive myoclonus epilepsies. Prog Brain Res. 2014;213:113-122.
Shahwan A, Farrell M, Delanty N. Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects. Lancet Neurol. 2005;4(4):239-248.
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.
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.
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.
Cameron JM, Ellis CA, Berkovic SF. ILAE genetics literacy series: progressive myoclonus epilepsies. Epileptic Disord. 2023;25:670-680.
Costa C, Oliver KL, Calvello C, Cameron JM, Imperatore V, Tonelli L, et al. IRF2BPL: a new genotype for progressive myoclonus epilepsies. Epilepsia. 2023;64(8):e164-e169.
Corbett MA, Schwake M, Bahlo M, Dibbens LM, Lin M, Gandolfo LC, et al. A mutation in the Golgi Qb-SNARE gene GOSR2 causes progressive myoclonus epilepsy with early ataxia. Am J Hum Genet. 2011;88(5):657-663.
Courage C, Oliver KL, Park EJ, Cameron JM, Grabińska KA, Muona M, et al. Progressive myoclonus epilepsies-residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes. Am J Hum Genet. 2021;108(4):722-738.
Canafoglia L, Franceschetti S, Gambardella A, Striano P, Giallonardo AT, Tinuper P, et al. Progressive myoclonus epilepsies: diagnostic yield with next-generation sequencing in previously unsolved cases. Neurol Genet. 2021;7(6):e641.
Muona M, Berkovic SF, Dibbens LM, Oliver KL, Maljevic S, Bayly MA, et al. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy. Nat Genet. 2015;47(1):39-46.
Nita DA, Mole SE, Minassian BA. Neuronal ceroid lipofuscinoses. Epileptic Disord. 2016;18(S2):73-88.
Azizieh R, Orduz D, Van Bogaert P, et al. Progressive myoclonic epilepsy-associated gene KCTD7 is a regulator of potassium conductance in neurons. Mol Neurobiol. 2011;44(1):111-121.
Moen MN, Fjaer R, Hamdani EH, et al. Pathogenic variants in KCTD7 perturb neuronal K+ fluxes and glutamine transport. Brain. 2016;139(Pt 12):3109-3120.
Van Bogaert P, Azizieh R, Desir J, et al. Mutation of a potassium channel-related gene in progressive myoclonic epilepsy. Ann Neurol. 2007;61(6):579-586.
Staropoli JF, Karaa A, Lim ET, Kirby A, Elbalalesy N, Romansky SG, et al. A homozygous mutation in KCTD7 links neuronal ceroid lipofuscinosis to the ubiquitin-proteasome system. Am J Hum Genet. 2012;91(1):202-208.
Mastrangelo M, Sartori S, Simonati A, et al. Progressive myoclonus epilepsy and ceroidolipofuscinosis 14: The multifaceted phenotypic spectrum of KCTD7-related disorders. Eur J Med Genet. 2019;62(12):103591.
Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, et al. Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Genet Med. 2017;19(10):1105-1117.
Richards S, Aziz N, Bale S, Bick D, das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424.
Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208.
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)-a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377-381.
Farhan SMK, Murphy LM, Robinson JF, Wang J, Siu VM, Rupar CA, et al. Linkage analysis and exome sequencing identify a novel mutation in KCTD7 in patients with progressive myoclonus epilepsy with ataxia. Epilepsia. 2014;55(9):e106-e111.
Metz KA, Teng X, Coppens I, Lamb HM, Wagner BE, Rosenfeld JA, et al. KCTD7 deficiency defines a distinct neurodegenerative disorder with a conserved autophagy-lysosome defect. Ann Neurol. 2018;84(5):766-780.
Binaafar S, Garshasbi M, Tavasoli AR, Badv RS, Hosseiny SMM, Samanta D, et al. Nonsyndromic early-onset epileptic encephalopathies: two novel KCTD7 pathogenic variants and a literature review. Dev Neurosci. 2021;43(6):348-357.
Blumkin L, Kivity S, Lev D, Cohen S, Shomrat R, Lerman-Sagie T, et al. A compound heterozygous missense mutation and a large deletion in the KCTD7 gene presenting as an opsoclonus-myoclonus ataxia-like syndrome. J Neurol. 2012;259(12):2590-2598.
Burke EA, Sturgeon M, Zastrow DB, Fernandez L, Prybol C, Marwaha S, et al. Compound heterozygous KCTD7 variants in progressive myoclonus epilepsy. J Neurogenet. 2021;35(2):74-83.
Dai L, Ding C, Fang F. Two Chinese siblings with two novel KCTD7 mutations have dystonia or seizures and epileptic discharge on electroencephalograms. Seizure. 2019;70:27-29.
Dudipala SC, Prashanthi M, Chennadi AK. A novel mutation in KCDT7 gene in an Indian girl with progressive myoclonus epilepsy. Cureus. 2021;13(2):e13447.
Kousi M, Anttila V, Schulz A, Calafato S, Jakkula E, Riesch E, et al. Novel mutations consolidate KCTD7 as a progressive myoclonus epilepsy gene. J Med Genet. 2012;49(6):391-399.
Kozina AA, Okuneva EG, Baryshnikova NV, Kondakova OB, Nikolaeva EA, Fedoniuk ID, et al. Neuronal ceroid lipofuscinosis in the Russian population: two novel mutations and the prevalence of heterozygous carriers. Mol Genet Genomic Med. 2020;8(7):e1228.
Krabichler B, Rostasy K, Baumann M, Karall D, Scholl-Bürgi S, Schwarzer C, et al. Novel mutation in potassium channel related gene KCTD7 and progressive myoclonic epilepsy. Ann Hum Genet. 2012;76(4):326-331.
Mei L, Huang Y, Chen J, He XM, Lin S, Liao L, et al. Exome sequencing identifies compound heterozygous KCTD7 mutations in a girl with progressivemyoclonus epilepsy. Clin Chim Acta. 2019;493:87-91.
Narayanan DL, Somashekar PH, Majethia P, Shukla A. KCTD7-related progressive myoclonic epilepsy: report of three Indian families and review of literature. Clin Dysmorphol. 2022;31(1):6-10.
Niu Y, Gong P, Jiao X, Xu Z, Zhang Y, Yang Z. Genetic and phenotypic spectrum of Chinese patients with epilepsy and photosensitivity. Front Neurol. 2022;13:907228.
Seaby EG, Gilbert RD, Pengelly RJ, Andreoletti G, Clarke A, Ennis S. Progressive myoclonic epilepsy with Fanconi syndrome. JRSM Open. 2016;7(6):2054270415623145.
Teng X, Aouacheria A, Lionnard L, Metz KA, Soane L, Kamiya A, et al. KCTD: a new gene family involved in neurodevelopmental and neuropsychiatric disorders. CNS Neurosci Ther. 2019;25(7):887-902.
Vairo FP, Boczek NJ, Cousin MA, Kaiwar C, Blackburn PR, Conboy E, et al. The prevalence of diseases caused by lysosome-related genes in a cohort of undiagnosed patients. Mol Genet Metab Rep. 2017;13:46-51.
Wang H, Lu Y, Dong X, Lu G, Cheng G, Qian Y, et al. Optimized trio genome sequencing (OTGS) as a first-tier genetic test in critically ill infants: practice in China. Hum Genet. 2020;139(4):473-482.
Wang J, Wen Y, Zhang Q, Yu S, Chen Y, Wu X, et al. Gene mutational analysis in a cohort of Chinese children with unexplained epilepsy: identification of a new KCND3 phenotype and novel genes causing Dravet syndrome. Seizure. 2019;66:26-30.
Large-scale discovery of novel genetic causes of developmental disorders. Nature. 2015;519(7542):223-228.
Alevy J, Burger CA, Albrecht NE, Jiang D, Samuel MA. Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function. Neurochem Int. 2019;129:104486.
Alfares A, Alfadhel M, Wani T, Alsahli S, Alluhaydan I, al Mutairi F, et al. A multicenter clinical exome study in unselected cohorts from a consanguineous population of Saudi Arabia demonstrated a high diagnostic yield. Mol Genet Metab. 2017;121(2):91-95.
Balint B, Bhatia KP. Myoclonus, epilepsy, and ataxia resulting from Potassium Channel gene mutation: expanding the Spectrum underlying Ramsay hunt syndrome. Mov Disord Clin Pract. 2015;2(3):230-231.
Butler KM, da Silva C, Alexander JJ, Hegde M, Escayg A. Diagnostic yield from 339 epilepsy patients screened on a Clinical gene panel. Pediatr Neurol. 2017;77:61-66.
Frésard L, Smail C, Ferraro NM, et al. Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts. Nat Med. 2019;25(6):911-919.
Helbig KL, Farwell Hagman KD, Shinde DN, Mroske C, Powis Z, Li S, et al. Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy. Genet Med. 2016;18(9):898-905.
Hu H, Kahrizi K, Musante L, Fattahi Z, Herwig R, Hosseini M, et al. Genetics of intellectual disability in consanguineous families. Mol Psychiatry. 2019;24(7):1027-1039.
Liang JH, Alevy J, Akhanov V, Seo R, Massey CA, Jiang D, et al. Kctd7 deficiency induces myoclonic seizures associated with Purkinje cell death and microvascular defects. Dis Model Mech. 2022;15(9):dmm049642.
Lindy AS, Stosser MB, Butler E, Downtain-Pickersgill C, Shanmugham A, Retterer K, et al. Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders. Epilepsia. 2018;59(5):1062-1071.
Muntean BS, Marwari S, Li X, Sloan DC, Young BD, Wohlschlegel JA, et al. Members of the KCTD family are major regulators of cAMP signaling. Proc Natl Acad Sci USA. 2022;119(1):e2119237119.
Rahman MM, Fatema K. Genetic diagnosis in children with epilepsy and developmental disorders by targeted gene panel analysis in a developing country. J Epilepsy Res. 2021;11(1):22-31.
Sawyer SL, Schwartzentruber J, Beaulieu CL, Dyment D, Smith A, Chardon JW, et al. Exome sequencing as a diagnostic tool for pediatric-onset ataxia. Hum Mutat. 2014;35(1):45-49.
Turro E, Astle WJ, Megy K, Gräf S, Greene D, Shamardina O, et al. Whole-genome sequencing of patients with rare diseases in a national health system. Nature. 2020;583(7814):96-102.
Van Bogaert P. KCTD7-related progressive myoclonus epilepsy. Epileptic Disord. 2016;18(S2):115-119.
Wang Y, Cao X, Liu P, Zeng W, Peng R, Shi Q, et al. KCTD7 mutations impair the trafficking of lysosomal enzymes through CLN5 accumulation to cause neuronal ceroid lipofuscinoses. Sci Adv. 2022;8(31):eabm5578.
Zhang J, Niu X, Chen J, et al. Clinical phenotype features and genetic etiologies of 38 children with progressive myoclonic epilepsy. Acta Epileptologica. 2020;2:14. https://doi.org/10.1186/s42494-020-00023-z
Specchio N, Ferretti A, Trivisano M, Pietrafusa N, Pepi C, Calabrese C, et al. Neuronal ceroid lipofuscinosis: potential for targeted therapy. Drugs. 2021;81(1):101-123.