GNAO1 Natural History Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Natural History of GNAO1-associated Neurodevelopmental Disorder

Conditions
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GNAO1

Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chorea | The Abnormal Involuntary Movement Scale (AIMS) assesses the severity of dyskinesias, as well as the overall severity, incapacitation, and the subject's level of awareness of the movements, and distress associated with them. | March 2019; May-Oct 2020 | 
| Dystonia | The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) assesses the severity of dystonia in nine body regions. The scale takes into account the severity and frequency of the dystonic movements. | March 2019; May-Oct 2020 | 
| Gross motor development, mobility | The Gross Motor Function Measure (GMFM-88) is a standardized observational instrument designed and validated to measure changes in gross motor function over time in children with cerebral palsy. | March 2019; May-Oct 2020 | 
| Spasticity | The Modified Ashworth Scale (MAS) is a muscle tone assessment scale used to assess the resistance experienced during passive range of motion. The MAS is the current standard for clinical assessment of extremity spasticity. | March 2019 | 
| Fine motor development | The Peabody Developmental Motor Scales 2nd Edition (PDMS-2) is an early childhood motor development program that provides both in-depth assessment and training or remediation of gross and fine motor skills. The assessment is composed of six subtests that measure interrelated motor abilities that develop early in life. We are mainly interested in two subtests: Grasping and Visual-Motor Integration. | March 2019 | 
| Quality of Life and Caregiver Burden | The Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire attempts to understand and quantitate the quality of life of patients and caregiver burden. | March 2019; May-Oct 2020 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Natural History Study, pediatric, neurology, movement disorder, epilepsy, GNAO1