Abstract

Introduction Pontocerebellar hypoplasia type 2A (PCH2A) is a rare neurogenetic disease causing severe cognitive and motor impairment. We report on brain morphometry and psychomotor development of affected children.

Materials and Methods We analyzed 78 cerebral MRI datasets of 57 patients with genetically proven PCH2A. Volumetry and in-plane measurements were performed in cerebellum, neocortex and pons. Supratentorial width and width of the anterior horns of the lateral ventricles was used to calculate the Evans index.

Caregivers of 65 patients with PCH2A (7 months to 33 years) filled in a survey assessing motor and cognitive development. Developmental status was compared to MRI measurements.

Results In children with PCH2A, cerebellar volume was markedly smaller than in healthy children at birth, with slower increase and stagnation at around 12 months. No cerebellar growth was observed in the cranio-caudal axis. Long-term data did not show a decrease in cerebellar volume or in-plane measurements. Supratentorial measurements showed progressive microcephaly and a continuous increase of the Evans index, indicating progressive cerebral atrophy. Patients showed severely impaired cognitive and motor development. Developmental regression was reported only for a minority. No statistical relationship between brain measurements and cognitive or motor development was observed.

Conclusion MRI of patients with PCH2A shows limited cerebellar growth during infancy, especially restricted along the cranio-caudal axis. After infancy, cerebellar volume remains relatively stable. Supratentorial measurements indicate slowly progressive atrophy. Psychomotor development is severely impaired, but regression is rare.

Highlights

- MRI (57 patients) and developmental data (65 patients) of children with PCH2A

- Cerebellar growth is affected in a spatial manner, resulting in the dragonfly sign

- Ongoing supratentorial atrophy, potentially secondary to cerebellar pathology

- Psychomotor development is delayed, but takes place and regression is rare

- No relation between brain measurements and developmental trajectories

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was supported by the Chan Zuckerberg initiative. The Chan Zuckerberg initiative was not involved in the design, conduct, interpretation or publication of this study.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee of University of Freiburg, Germany gave ethical approval for this work (decision no. 20-1040) Ethics committee of the University of Tuebingen (decision no. 105/2012BO2) gave ethical approval for this work.

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Data Availability

All data produced in the present study are available upon reasonable request to the authors.

AbbreviationsCIConfidence IntervalICCIntraclass Correlation CoefficientLOESSLocal Estimated Scatterplot SmoothingmRNAmessenger RNAPCHPontocerebellar hypoplasiaPCH2APontocerebellar hypoplasia type 2AtRNAtransfer RNA