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Analysis of the Clinical Features and Imaging Findings of Pontocerebellar Hypoplasia Type 2D Caused by Mutations in SEPSECS Gene

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Abstract

Pontocerebellar hypoplasia type 2D (PCH2D) caused by SEPSECS gene mutations is very rare and only described in a few case reports. In this study, we analyzed the clinical features and imaging findings of these individuals, so as to provide references for the clinic. We reported a case of PCH2D caused by a new complex heterozygote mutation in SEPSECS gene, and reviewed the literatures to summarize the clinical features and imaging findings and compare the differences between early-onset patients (EOPs) and late-onset patients (LOPs). Of 23 PCH2D patients, 19 cases were early-onset and 4 cases were late-onset, with average ages of 4.1 ± 4.0 years and 21.8 ± 9.4 years, females were more prevalent (14/19). EOPs mainly distributed in Arab countries (10/14) and Finland (4/14), while LOPs in East Asia (3/3). EOPs develop severe initial symptoms at the average age of 4.1 ± 7.8 months or shortly after birth, while LOPs experienced mild developmental delay in infancy. Microcephaly (10/11), intellectual disability (10/11), decreased motor function (10/11), and spastic or dystonic quadriplegia (8/10) were the common clinical features of EOPs and LOPs. EOPs also presented with visual impairment (5/7), seizures (4/7), neonatal irritability/opisthotonus (3/7), tremors/myoclonus (3/7), dysmorphic features (3/7), and other symptoms. EOPs were characterized by cerebellar symptoms (4/4). Magnetic resonance imaging (MRI) revealed progressive cerebellar atrophy followed by less pronounced cerebral atrophy, and there was no pons atrophy in LOPs. Most patients of PCH2D were severe early-onset, and a few were late-onset with milder symptoms. EOPs and LOPs shared some common clinical features and MRI findings, but also had their own characteristics.

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All data generated or analyzed during this study are included in this published article and its supplementary Material.

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Ran Zhao, Limin Zhang & Hong Lu

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  1. Ran Zhao
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  2. Limin Zhang
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  3. Hong Lu
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Contributions

Ran Zhao analyzed the data and drafted the manuscript. The study concept and design were done by Hong Lu and Limin Zhang. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hong Lu.

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Ethical Approval

This study was approved by the medical research ethics board of the First Affiliated Hospital of Zhengzhou University. Written informed consent was obtained from our patient and her parents. All methods in the study were performed in accordance with World Medical Association Declaration of Helsinki and its later amendments.

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The authors declare no competing interests.

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Zhao, R., Zhang, L. & Lu, H. Analysis of the Clinical Features and Imaging Findings of Pontocerebellar Hypoplasia Type 2D Caused by Mutations in SEPSECS Gene. Cerebellum 22, 938–946 (2023). https://doi.org/10.1007/s12311-022-01470-9

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