Rare Genetic Ataxias in Childhood and Future Implications for Curing Gene Therapy Options

Abstract

Rare genetic ataxias in childhood are usually progressive neurological disorders characterized by coordination problems (balance/gait instability, fine motor skills) due to damage to the cerebellum. Ataxias are movement disorders that mainly originate from the cerebellum and its connections, leading to a coordination disorder. The first symptom usually perceived by the patient is instability in standing and walking. As the condition progresses, speech and limb coordination disturbances occur, often manifesting as changes in fine motor skills. Speech becomes slow and slurred, and early eye movement disorders are common. Other neurological and non-neurological symptoms may also occur. Diagnosis relies on medical history, neurological examination, and cranial magnetic resonance imaging, followed by molecular genetic and possibly biochemical tests. The low prevalence and marked heterogeneity of ataxias complicate the diagnostic process. Ataxias can be classified into acquired ataxias (e.g., metabolic/toxic, immune-mediated), sporadic degenerative ataxias with cerebellar-type multisystem atrophy, or genetically inherited ataxias (e.g., Friedreich's ataxia, spinocerebellar ataxias). Early diagnosis is crucial to avoid unnecessary testing and provide appropriate patient counseling. Specific therapies are available for certain ataxias and symptoms, and rehabilitative therapies are essential components of treatment. In childhood, common forms include ataxia-telangiectasia, Niemann Pick type C, episodic and spinocerebellar ataxias. Diagnosis involves MRI, neurological examinations, and genetic tests, as therapies are rarely causative but increasingly gene-based research is being explored. Genetic ataxias are usually not curable, but research is focusing on gene therapies and molecular approaches. Occupational therapy, physiotherapy, and speech therapy are essential to maintain mobility and quality of life for as long as possible. This manuscript is an overview of rarely found ataxia types in childhood.