{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T12:21:37Z","timestamp":1777292497872,"version":"3.51.4"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Mutations in the dynein cytoplasmic 1 heavy chain 1 (<jats:italic>DYNC1H1<\/jats:italic>) 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 <jats:italic>DYNC1H1<\/jats:italic> and review the relevant literature to explore genotype-phenotype relationships.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>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 <jats:italic>de novo<\/jats:italic> heterozygous mutation (p.Arg292Trp) in the <jats:italic>DYNC1H1<\/jats:italic> gene was identified. A search of multiple databases, including PubMed and Embase, using the search strategy <jats:italic>DYNC1H1<\/jats:italic> 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 <jats:italic>DYNC1H1<\/jats:italic>-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%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MCD, particularly pachygyria, is a common neurodevelopmental disorder in patients with <jats:italic>DYNC1H1<\/jats:italic> 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 <jats:italic>DYNC1H1<\/jats:italic> mutations may experience central nervous system (CNS) manifestations due to MCD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1163803","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T05:18:42Z","timestamp":1682399922000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Case report: Genotype and phenotype of DYNC1H1-related malformations of cortical development: a case report and literature 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