dync1h1-related Epilepsy in a Chinese Cohort: Novel Variants and Genotype-phenotype Correlation
Abstract number :
1.207
Submission category :
4. Clinical Epilepsy / 4B. Clinical Diagnosis
Year :
2022
Submission ID :
2204140
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:23 AM
Authors :
文伟 刘, MD – Peking University First Hospital; Miaomiao Cheng, PhD – Peking University First Hospital; hui Chen, doctor – Department of Neurology, Chengdu Women and Children’s Central Hospital; Ying Zhu, Professer – Peking University First Hospital; yi chen, MD – Peking University First Hospital; xiaojuan tian, MD – 4. Department of Neurology, Beijing Children's Hospital, Capital Medical University; xueyang niu, PhD – Peking University First Hospital; Ying yang, PhD – Peking University First Hospital; xiaoling yang, PhD – Peking University First Hospital; yuehua zhang, Professer – Peking University First Hospital
Rationale: DYNC1H1 (OMIM: 600112) is located in 14q32.31, encodes for Dynein cytoplasmic 1 heavy chain 1 (DYNC1H1), the core subunit of cytoplasmic dynein complex 1. The protein, which contains motor domain, stem domain, and neck domain, acts as a microtubules-associated protein and retrograde transports the cargo along the microtubule scaffold in axons. (Gonçalves et al., 2018) DYNC1H1 variants were reported to cause many clinical manifestations, including epilepsy, brain developmental diseases, spinal muscular atrophy-lower extremity predominant (SMALED), Charcot-Marie-Tooth disease (CMT), hereditary spastic paraplegia (HSP), cataracts, Parkinson’s disease, developmental delay/intellectual disability, and cancer. (Amabile et al., 2020) This study aimed to explore the phenotypic spectrum and refine the genotype-phenotype correlation of DYNC1H1-related epilepsy._x000D_
Methods: The clinical data of 14 epileptic patients in our cohort and 50 epileptic patients from 24 published studies with DYNC1H1variants were evaluated.
Results: In our cohort, 12 variants were identified from 14 patients. 11 variants were de novo, eight were novel. Age at seizure onset ranged from 5 mo to 4 yr 5mo (median age 1 yr). The common seizure types were epileptic spasms, focal seizures, tonic seizures, and myoclonic seizures. Mild to severe developmental delays were present in all patients. Five patients were diagnosed with West Syndrome, and one was diagnosed with epileptic encephalopathy with continuous spikes and waves during slow sleep (CSWS). Collectively, in our cohort and the published studies, 17% of the patients had ophthalmic diseases. 56% of the variants affected the protein in motor domain, where 53% of variants located in stalk domain. 92% epileptic patients had a malformation of cortical dysplasia (MCDs), in which pachygyria and pachygyria/ agyria were the most common phenotypes, accounting for 61% of the MCDs._x000D_
Conclusions: DYNC1H1-related epilepsy included multiple seizure types. The common seizure types included focal seizure, epileptic spasm, myoclonic seizure, and tonic seizure. More than 10% of patients can be diagnosed with West syndrome. LGS and CSWS were rare epileptic syndrome related to the DYNC1H1 variant. Most of the patients had MCDs. Pachygyria and malformation in the corpus callosum, brainstem, cerebellum and basal ganglia are the major features of MCDs. The majority of epileptic patients with DYNC1H1 variants were drug-resistant. Nearly 20% of patients had ophthalmic diseases with the most common features of unilateral or bilateral cataracts._x000D_
Funding: None
Clinical Epilepsy