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

Wen-Rong Ge; Pei-Pei Fu; Wei-Na Zhang; Bo Zhang; Ying-Xue Ding; Guang Yang

doi:10.3389/fneur.2023.1163803

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

Front Neurol. 2023 Apr 25:14:1163803. doi: 10.3389/fneur.2023.1163803. eCollection 2023.

Authors

Wen-Rong Ge¹, Pei-Pei Fu¹, Wei-Na Zhang¹, Bo Zhang², Ying-Xue Ding¹, Guang Yang^{3

4

5}

Affiliations

¹ Department of Pediatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
² Department of Neurology and ICCTR Biostatistics and Research Design Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
³ Senior Department of Pediatrics, The Seventh Medical Center of People's Liberation Army General Hospital, Beijing, China.
⁴ Department of Pediatrics, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.
⁵ The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Abstract

Background: Mutations 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 presentation: A 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%).

Conclusion: MCD, 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.

Keywords: DYNC1H1 gene; case report; malformations of cortical development; microtubule-binding domain; variant.

Publication types

Case Reports

Grants and funding

This study was partly financed by the Beijing Natural Science Foundation (No. 7222187), Medical Big Data and Artificial Intelligence Research and Development Project of the Chinese People's Liberation Army General Hospital (No. 2019MBD-004), Epilepsy Research Fund of China Association Against Epilepsy (No. CU-B-2021-11), and Nutrition and Care of Maternal and Child Research Fund Project of Guangzhou Biostime Institute of Nutrition and Care (No. 2021BINCMCF030).