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Classic “PCH” Genes are a Rare Cause of Radiologic Pontocerebellar Hypoplasia

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Abstract

The term Pontocerebellar Hypoplasia (PCH) was initially used to designate a heterogeneous group of fetal-onset genetic neurodegenerative disorders. As a descriptive term, PCH refers to pons and cerebellum of reduced volume. In addition to the classic PCH types described in OMIM, many other disorders can result in a similar imaging appearance. This study aims to review imaging, clinical and genetic features and underlying etiologies of a cohort of children with PCH on imaging. We systematically reviewed brain images and clinical charts of 38 patients with radiologic evidence of PCH. Our cohort included 21 males and 17 females, with ages ranging between 8 days to 15 years. All individuals had pons and cerebellar vermis hypoplasia, and 63% had cerebellar hemisphere hypoplasia. Supratentorial anomalies were found in 71%. An underlying etiology was identified in 68% and included chromosomal (21%), monogenic (34%) and acquired (13%) causes. Only one patient had pathogenic variants in an OMIM listed PCH gene. Outcomes were poor regardless of etiology, though no one had regression. Approximately one third of patients deceased at a median age of 8 months. All individuals had global developmental delay, 50% were non-verbal, 64% were non-ambulatory and 45% required gastrostomy feeding. This cohort demonstrates that radiologic PCH has heterogenous etiologies and the “classic” OMIM-listed PCH genes underlie only a minority of cases. Broad genetic testing, including chromosomal microarray and exome or multigene panels, is recommended in individuals with PCH-like imaging appearance. Our results strongly suggest that the term PCH should be used to designate radiologic findings, and not to imply neurogenerative disorders.

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Acknowledgements

M Srour holds a salary award from the Fonds de Recherche de Santé Quebec.

Funding

The authors did not receive support from any organization for the submitted work.

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Authors and Affiliations

  1. Division of Pediatric Neurology, Department of Pediatrics, McGill University, Montreal, Quebec, Canada

    Rohaya Binti Mohamad Zakaria & Myriam Srour

  2. Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada

    Maisa Malta, Nassima Addour-Boudrahem & Myriam Srour

  3. Division of Child Neurology, Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo, Brazil

    Maisa Malta

  4. Division of Pediatric Neurology, Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada

    Felixe Pelletier & Elana Pinchefsky

  5. Department of Radiology, McGill University, Montreal, Quebec, Canada

    Christine Saint Martin

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  1. Rohaya Binti Mohamad Zakaria
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Contributions

Conceptualization: Myriam Srour, Rohaya Zakaria. First draft of the manuscript: Rohaya Zakaria and Maisa Malta. Data collection: Rohaya Zakaria, Maisa Malta, Felixe Pelletier. Imaging review: Christine Saint-Martin. Supervision: Myriam Srour, Elana Pinchefsky. All authors contributed to critical feedback, revision, and final approval of the manuscript.

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Correspondence to Myriam Srour.

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Ethical Approval

This study was approved by our institutional research ethics boards (McGill University Health Center MP-2021–6580; Centre Hospitalier Universitaire Sainte Justine MEO-37–2021-2915). Our REB waived the requirement for signed patient consent as the study does not include any identifiable images or information.

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The authors declare that they have no competing interests.

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Rohaya Binti Mohamad Zakaria and Maisa Malta have equal contribution as co-first authors.

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Zakaria, R.B.M., Malta, M., Pelletier, F. et al. Classic “PCH” Genes are a Rare Cause of Radiologic Pontocerebellar Hypoplasia. Cerebellum 23, 418–430 (2024). https://doi.org/10.1007/s12311-023-01544-2

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