BACKGROUND

GNAO1 encodes an alpha-subunit of heterotrimeric G-proteins abundantly expressed in brain tissue, especially neuronal synapses. Since 1998, GNAO1 mutations have been reported with a phenotype characterized by early infantile epileptic encephalopathy. Later a new phenotype was described with progressive movement disorder without epilepsy. These patients exhibited severe chorea, developmental delay, and hypotonia.

A variety of medications have been used to treat pediatric patients with severe chorea without success. Finally, deep brain stimulation (DBS) was report in some cases of GNAO1 mutation with effective control of the movement disorder.

OBJECTIVE

Describe the clinical manifestation of GNAO1 mutation and its response to bilateral DBS.

MATERIAL AND METHODS

We present a 6-year-old girl withglobal developmental delay and hypotonia from infancy. Chorea developed by age four years, initially in intermittent periods. The chorea became gradually progressive and marked by episodes of severe, refractory ballismus requiring intensive care unit admissions. All complementary studies were negative but whole exome sequencing confirmed a novel mutation in GNAO1.

Treatments with neuroleptics and tetrabenazine were not effective and the movement disorder became refractory to maximum medical therapy, so bilateral Gpi DBS wasperformed without complicationand the movement stopped with initiation of stimulation.

CONCLUSIONS:Patients with GNAO1 mutations can present with a severe, progressive movement disorder in the absence of epilepsy. Exacerbations may be refractory to treatment and can result in life-threatening secondary complications. Early recognition and genetic confirmation can lead to DBS resulting in a significant reduction of movement.