Patients with pontocerebellar hypoplasia 6 (PCH6) present with global developmental delay and neonatal-onset intractable seizures of variable type. Hypoplasia/atrophy of the cerebellum and/or cerebrum are characteristic of this disorder, with nearly 50% of cases featuring additional neurodegenerative changes in the pons. Other common phenotypes include acquired microcephaly, intellectual disability, hypotonia, feeding difficulties, ataxia, hyperreflexia/spasticity, elevated lactate in the blood or cerebrospinal fluid, neonatal hypoglycemia, and impaired respiratory chain activity. Dystonia, edema, optic atrophy, apneic episodes, and facial dysmorphisms (such as full cheeks and deep-set eyes) have also been reported.
Recently, less severe RARS2-associated phenotypes were described in patients who initially demonstrated normal development. Developmental concerns and features suggestive of a movement disorder (i.e., myoclonus, abnormal eye movements, dysarthria, and ataxic gait) arose in early childhood, followed by seizure onset. In at least one such patient, the seizures were successfully controlled by pharmacological intervention.
RARS2