The purpose of the GNAO1 Natural History Study is to establish the clinical phenotype of GNAO1 associated neurologic disease, its association with genotype, and areas of clinical importance within the disease.

GNAO1 associated neurologic disease is a rare autosomal dominant neurodevelopmental disorder characterized genetically by heterozygous de novo mutations in GNAO1 gene which encodes Gαo, the α subunit of Go, a G protein signal transducer. Phenotypically, it is characterized by developmental delay, epilepsy and/or movement disorder. Medical therapy is symptomatic and often ineffective for many patients. While there are basic and translational studies underway to develop more mechanistic treatments aimed at developing disease modifying treatments, our general knowledge of the natural history of GNAO1 associated neurologicis is extremely limited, making it difficult to select the best measures for identifying changes over time. Without this information,it will be difficult to detect any potential therapeutic efficacy in future trials of novel therapies. To address this critical void in our understanding, we propose to retrospectively and prospectively examine symptom progression(short-and long-term)and developmental outcomes in patients with GNAO1 associated neurologic disease. Retrospective data will be collected on a cohort of 50 patients. Standardized historical clinical information will be received from the physicians and care-givers of these patients, in collaboration with the Bow Foundation Registry. These data will provide an overview of the onset and severity of symptoms over development. In addition, prospective data will be acquired during in-person clinical evaluations of a cohort of 15-20 patients who are not receiving any experimental interventions. In combination, these two approaches will provide critical information about the natural history of GNAO1 associated neurologic disease in children, identify metrics that track change most reliably over time, and collect pilot data for larger future studies.

Inclusion Criteria:

• Enrollment in the Bow Foundation GNAO1 registry.
• Evidence of a known pathogenic mutation in GNAO1 or a variant of unknown significance and clinical symptoms likely to be consistent with GNAO1 as determined by study physicians.

Exclusion Criteria:

• Inability to obtain informed consent from parents or adult subjects.
• Inability to obtain medical records.

Minors and adults who have a confirmed pathogenic mutation in GNAO1 or a variant of unknown significance and clinical symptoms likely to be consistent with GNAO1 (e.g. global developmental delay, movement disorder, seizures) as determined by study physicians.