Unlocking the Mysteries of Oculomotor Apraxia: Genetic Testing and Beyond

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Oculomotor apraxia (OA) is a rare neurological disorder that affects the ability to coordinate eye movements, leading to difficulties in tracking objects or shifting gaze between two points. While OA can occur in isolation, it is often associated with other neurological conditions such as ataxia, dystonia, and epilepsy. In recent years, advances in genetic testing have allowed for a more accurate and comprehensive understanding of the underlying genetic causes of OA, leading to improved diagnostic and treatment options for affected individuals.

Understanding Oculomotor Apraxia

OA is characterized by the inability to initiate or control voluntary eye movements, often resulting in a compensatory head thrust to shift gaze. This condition can manifest in various forms, such as ataxia with oculomotor apraxia type 2 (AOA2) and ataxia-telangiectasia-like disorder 1 (ATLD1). AOA2 is caused by mutations in the SETX gene, while ATLD1 is associated with mutations in the MRE11 gene. Both conditions often present with additional neurological symptoms, including ataxia, dystonia, and polyneuropathy.

Diagnosing Oculomotor Apraxia

Diagnosing OA can be challenging due to its rarity and the variability of its presentation. A thorough clinical evaluation, including a detailed patient history, physical examination, and assessment of eye movements, is essential for identifying OA. However, genetic testing has emerged as a valuable tool for confirming OA diagnoses and identifying the specific genetic mutations responsible for the disorder.

Genetic Testing for AOA2

A recent study identified a novel homozygous missense mutation in the SETX gene causing AOA2 in two Pakistani families. This discovery not only confirms the genetic basis of AOA2 but also expands our understanding of the SETX gene’s role in the development of the disorder. Genetic testing for SETX mutations can facilitate early and accurate diagnosis of AOA2, allowing for appropriate medical intervention and management.

Genetic Testing for ATLD1

In a unique case report, a 45-year-old woman was diagnosed with ATLD1 without oculomotor apraxia after presenting with cervical and facial dystonia, dysarthria, and ataxia. This finding highlights the importance of considering ATLD1 as a potential cause of OA, even in the absence of oculomotor apraxia. Genetic testing for MRE11 mutations can help identify ATLD1 and guide appropriate treatment strategies.

Recent research has also identified new genetic mutations and disorders associated with OA, further expanding the spectrum of OA-related conditions. For example, a study describing two siblings with RARS2 gene mutations found that these mutations can cause myoclonic epilepsy, mental retardation, spasticity, and extrapyramidal features. This discovery broadens our understanding of the range of disorders that can be linked to OA and underscores the importance of genetic testing for accurate diagnosis and management.

De Novo SETX Variant and Severe Polyneuropathy

Another study reported two unrelated patients with the same de novo SETX variant presenting with early-onset, severe polyneuropathy. This finding expands the clinical spectrum of SETX-related disorders and highlights the importance of considering SETX mutations in patients with unexplained polyneuropathy and OA.

Conclusion

Genetic testing has significantly advanced our understanding of the complex genetic landscape of oculomotor apraxia and related disorders. By identifying the specific genetic mutations responsible for OA, clinicians can provide more accurate diagnoses and tailor treatment plans to address the unique needs of affected individuals. As research continues to uncover new genetic mutations and associations with OA, genetic testing will play an increasingly vital role in the diagnosis and management of this rare and complex disorder.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)