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Pontocerebellar hypoplasia type 1: new leads for an earlier diagnosis
Michael S Salman1, Susan Blaser, J Raymond Buncic
1Department of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada. Michael.Salman@sickkids.ca
Insights
Pontocerebellar hypoplasia type 1 involves pontocerebellar hypoplasia and anterior horn cell degeneration. New findings suggest progressive neurodegeneration and abnormal electroretinograms, expanding the disease
Area of Science:
- Neurology
- Genetics
- Rare Diseases
Background:
- Pontocerebellar hypoplasia type 1 (PCH1) is a rare neurodevelopmental disorder.
- Characterized by pontocerebellar hypoplasia and anterior horn cell degeneration.
- Previous cases reported early mortality, typically before 2.5 years of age.
Observation:
- Two siblings with PCH1 presented with global developmental delay and hypotonia.
- Clinical course included respiratory failure and pneumonia.
- Autopsy revealed anterior horn cell degeneration.
Findings:
- Extensive metabolic and genetic testing ruled out known inherited disorders.
- Electroretinography showed novel, progressive rod/cone dysfunction.
- This suggests a neurodegenerative component in PCH1.
Implications:
- The findings expand the known phenotype of pontocerebellar hypoplasia type 1.
- Highlights the importance of electroretinography in diagnosing PCH1.
- Suggests a broader spectrum of neurodegeneration in PCH1 patients.
Abstract:
Pontocerebellar hypoplasia type 1 is a rare disease characterized by pontocerebellar hypoplasia and anterior horn cell degeneration. The oldest reported child died at the age of 26 months. Two siblings were diagnosed with pontocerebellar hypoplasia type 1 after the death of the second sibling at 40 months of age from respiratory failure and the unexpected finding of anterior horn cell degeneration on her autopsy. The older sibling was a boy who was labeled as having cerebral palsy. He died at 14 months of age from pneumonia following a clinical course similar to his sister's, who was born 5 years after his death. Both siblings had significant global developmental delay with axial and peripheral hypotonia initially. Peripheral hypertonia with brisk reflexes developed later but were absent prior to death. Extensive investigations in the second sibling ruled out known metabolic (including congenital disorders of glycosylation) and mitochondrial diseases using skin fibroblast cultures and enzyme analysis. Genetic testing for Friedreich's ataxia; neuropathy, ataxia, and retinitis pigmentosa (NARP); spinal muscular atrophy; and spinocerebellar ataxia type 1, 2, 3, 6, 7, and 8 gene abnormalities was negative. The elecroretinogram showed a previously unreported finding of abnormal and progressive rod/cone response. Our cases provide clinical and previously unreported electroretinographic evidence for neurodegeneration in pontocerebellar hypoplasia type 1 and call for the expansion of the disease phenotype.