Ataxia with oculomotor apraxia type 2: two pedigree studies and a comprehensive review.

Background: Ataxia with oculomotor apraxia type 2 (AOA2), a rare autosomal recessive neurodegenerative disorder, exhibits marked clinical heterogeneity, thereby presenting substantial diagnostic challenges. This study conducts an investigation of two pedigrees with SETX gene mutation-associated AOA2, coupled with a review of the clinical manifestations and genetic characteristics documented in previously reported study.

Methods: Clinical data were collected from probands and their respective family members. A systematic literature review of AOA2 cases was conducted utilizing the PubMed, Google Scholar, and Web of Science databases to analyze the clinical and genetic characteristics.

Results: Both pedigrees exhibited progressive gait instability, dysarthria, peripheral neuropathy, cerebellar atrophy, and elevated α-fetoprotein (AFP). Genetic testing identified a homozygous c.7034_7036delTAA mutation in Pedigree A and compound heterozygous mutations (c.6812A > G and exon7-10 deletion) in Pedigree B. Literature review of 216 patients revealed median onset age of 15 years old (interquartile range: 13-18), with 77.1% developing symptoms between 10 and 20 years. Key clinical features included ataxia (100%), dysarthria (99.2%), cerebellar atrophy (99.4%), and elevated AFP (97.6%). Oculomotor apraxia was observed in 34.2% of cases. Disease progression to wheelchair dependence averaged 15.9 ± 8.6 years, with no significant differences observed in gender or adult onset and juvenile onset.

Conclusions: We identified novel SETX mutations in patients with AOA2. Notably, oculomotor apraxia is not always a clinical manifestation of AOA2 at diagnosis. Mild elevation of AFP could serve as a valuable diagnostic indicator in people with hereditary ataxia. Disease progression to wheelchair dependence may not be correlated with gender and age of onset.