DYNC1H1 variant associated with epilepsy: Expanding the phenotypic spectrum

Chung, Chi-Ting; Lee, Ni‐Chung; Fan, Shixiong; Hung, Miao‐Zi; Lin, Yen‐Heng; Chen, Chih‐Hao; Jao, Tun

doi:10.1016/j.ebr.2022.100580

Cited by 2 publications

(1 citation statement)

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“…These processes include Golgi apparatus regulation, cargo transport, axonal transport, spindle pole organization, organelle motility, and nuclear migration throughout mitosis (1,2). DYNC1H1 mutations are associated with various clinical manifestations that are typically divided into two major categories: central nervous system (CNS) symptoms (e.g., malformations of cortical development [MCD], intellectual developmental disorder, and developmental and epileptic encephalopathy [DEE]) (3)(4)(5)(6)(7)(8); and neuromuscular diseases (e.g., spinal muscular atrophy [SMA] with predominance in the lower extremities and Charcot-Marie-Tooth [CMT], type 20 (1,2,9,10).…”

Section: Introductionmentioning

confidence: 99%

Case report: Genotype and phenotype of DYNC1H1-related malformations of cortical development: a case report and literature review

Zhang

et al. 2023

Front. Neurol.

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BackgroundMutations in the dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene are linked to malformations of cortical development (MCD), which may be accompanied by central nervous system (CNS) manifestations. Here, we present the case of a patient with MCD harboring a variant of DYNC1H1 and review the relevant literature to explore genotype-phenotype relationships.Case presentationA girl having infantile spasms, was unsuccessfully administered multiple antiseizure medications and developed drug-resistant epilepsy. Brain magnetic resonance imaging (MRI) at 14 months-of-age revealed pachygyria. At 4 years-of-age, the patient exhibited severe developmental delay and mental retardation. A de novo heterozygous mutation (p.Arg292Trp) in the DYNC1H1 gene was identified. A search of multiple databases, including PubMed and Embase, using the search strategy DYNC1H1 AND [malformations of cortical development OR seizure OR intellectual OR clinical symptoms] up to June 2022, identified 129 patients from 43 studies (including the case presented herein). A review of these cases showed that patients with DYNC1H1-related MCD had higher risks of epilepsy (odds ratio [OR] = 33.67, 95% confidence interval [CI] = 11.59, 97.84) and intellectual disability/developmental delay (OR = 52.64, 95% CI = 16.27, 170.38). Patients with the variants in the regions encoding the protein stalk or microtubule-binding domain had the most prevalence of MCD (95%).ConclusionMCD, particularly pachygyria, is a common neurodevelopmental disorder in patients with DYNC1H1 mutations. Literature searches reveales that most (95%) patients who carried mutations in the protein stalk or microtubule binding domains exhibited DYNC1H1-related MCD, whereas almost two-thirds of patients (63%) who carried mutations in the tail domain did not display MCD. Patients with DYNC1H1 mutations may experience central nervous system (CNS) manifestations due to MCD.

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