Progressive cerebello-cerebral atrophy

Progressive cerebello-cerebral atrophy (PCCA), also known as progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome) or PEHO-like syndrome in some overlapping classifications, is a severe neurodegenerative disorder characterized by progressive atrophy of both the cerebellum and cerebral cortex. The condition is caused by biallelic mutations in the SEPSECS gene (also known as PCH2D in some nosologies) or related genes depending on the specific subtype, and it primarily affects the central nervous system. Affected individuals typically present in early infancy with profound developmental delay, progressive microcephaly, severe intellectual disability, hypotonia, and seizures that may include infantile spasms. Cerebellar atrophy is a hallmark finding on brain imaging, often accompanied by progressive cerebral cortical atrophy. The neurological deterioration is relentless, with affected children failing to achieve or losing developmental milestones. Additional features may include optic atrophy leading to visual impairment, feeding difficulties requiring nutritional support, and spasticity that develops over time. Some patients may also exhibit dysmyelination or white matter abnormalities on MRI. The condition significantly impacts quality of life and life expectancy, with many affected individuals requiring comprehensive supportive care from early in life. There is currently no curative treatment or disease-modifying therapy for progressive cerebello-cerebral atrophy. Management is entirely supportive and symptomatic, focusing on seizure control with antiepileptic medications, nutritional support (often via gastrostomy tube), physical therapy to manage spasticity and contractures, and multidisciplinary care to address the complex medical needs of affected individuals. Genetic counseling is recommended for families, as the condition follows an autosomal recessive inheritance pattern.

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