Ataxia, a neurological symptom characterized by loss of coordinated movements, can be genetic, acquired, or idiopathic. Ataxia is clinically classified into Early-Onset Ataxia (EOA) and Late-Onset Ataxia (LOA), based on symptom-onset before or after 25 years of age. The phenotype of ataxia may also be present in other movement- and neurodevelopmental disorders, such as dystonia and Developmental Coordination Disorder (DCD). Dystonia is characterized by involuntary muscle contractions causing abnormal postures or repetitive movements. DCD is a descriptive term involving children with coordination impairments unexplained by an underlying neurological disorder. EOA, LOA, dystonia and DCD may all present with similar coordination impairments. Moreover, ataxia and dystonia co-occur in 65% of children and young adults with coordination impairments of various etiology. This frequent co-occurrence limits the uniform clinical recognition of EOA compared to other disorders associated with impaired coordination, including LOA, dystonia and DCD. Also, this co-occurrence suggests the existence of a pathogenetic and clinical continuum between these four conditions.
This thesis of Martinica Garofalo focuses on genetic EOA and explores its relationship with LOA, dystonia and DCD. The first part explores the underlying genetic, anatomical, and biological pathways of these four conditions. The second part focuses on the challenging clinical and diagnostic distinction of coordination impairments described as DCD from other neurological disorders, including EOA, LOA and dystonia. The findings of this thesis point to shared pathogenetic mechanisms and reveal the presence of a unified clinical continuum between EOA, LOA, dystonia and DCD.
These data advocate for a unified diagnostic approach in pediatric movement- and neurodevelopmental disorders, through the implementation of genetic and neuroimaging assessments. This may improve patient care through earlier disease identification and disease-specific interventions.
