Objective: We describe the clinical course of 6 patients with de novo GNAO1 mutations with severe chorea, developmental delay and hypotonia, but the absence of epilepsy.

Background: Mutations in GNAO1 (16q12.2), which encodes a Gαo subunit of heterotrimeric G proteins, have been described to date in eight patients with epileptic encephalopathy. Two patients had a severe movement disorder as the prominent feature.

Methods: We describe the clinical presentation, laboratory evaluations, neuroimaging findings, and one autopsy report of 6 patients (from 3 separate institutions) with mutations in GNAO1.

Results: In all 6 patients, global developmental delay and hypotonia were present from infancy, with onset of chorea around age 3-4 years. None had a history of seizures. Initial clinical brain MRI in all cases was normal; repeat imaging in three patients showed global volume loss. The chorea was progressive and marked with bouts of severe refractory ballismus, requiring ICU admissions in 5 out of 6 patients. Uncontrolled chorea and ballismus indirectly led to the death of 2 of the patients at ages 4.5 and 10. Limited autopsy in the patient who died at age 10 showed global cerebral volume loss with evidence of periventricular gliosis.

Conclusions: Patients with GNAO1 mutations can present with a severe, progressive chorea in the absence of epilepsy. Exacerbations may be refractory to treatment and can result in life threatening secondary complications. Neuroimaging and one autopsy suggest that this may be a neurodegenerative disorder.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-course-and-treatment-of-6-children-with-gnao1-mutations-causing-a-severe-life-threatening-chorea/