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Título

A RARE CAUSE OF NEURODEVELOPMENTAL DISORDER WITH INVOLUNTARY MOVEMENTS: GNAO1 ENCEPHALOPATHY

RESUMO

Case Presentation: A 6 years old girl born from vaginal delivery, at term, by the age of 8 months started with involuntary hyperkinetic jerk movements most notably in the hands, and jaw, especially when anxious, with progression of symptoms. Crawling and sitting at the age of 2 years old and first words at the age of 5. At the age of 6, the patient was admitted to the current service and parents reported anxious behavior and worsening of the chewing movements and uncoordinated arm movements. Neurological examination showed axial hypotonia, compromising trunk sustentation, sialorrhea, uncoordinated crawling,chewing movements, Babinski sign and achilles tendon shortening. A full exome sequencing was performed, demonstrating, in heterozygous, the variant chr16:56.351.397 A>T (or alternatively c.737A>T - ENST00000262493), which promotes que substitution of the glutamate amino-acid by a valine on the codon 246 (p.Glu246Val) in GNAO1 (OMIM 139311). This variant has never been described in the medical literature.
Discussion: GNAO1 encodes the alpha subunit of the Go subclass of heterotrimeric guanine nucleotide-binding proteins (G proteins), which is expressed in the brain and has an important role in the regulation of neuronal excitability and neurotransmission. Heterozygous mutations in GNAO1 are associated with a wide range of manifestations, from Developmental and Epileptic Encephalopathy-17 (DEE17) to significant Neurodevelopmental Disorder with Involuntary Movements (NEDIM). Patients with NEDIM may present with severe choreoathetosis, developmental delay, and hypotonia. The hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, high ambient temperature, and specific emotions, such as anxiety, a phenotype similar to that of the patient described herein.
Final comments: Our study reports a Brazilian patient with NEDIM, confirming the association between the GNAO1 p.Glu246Val pathogenic variant and this phenotype, which has not been described before in the literature. Therefore, we encourage that GNAO1 pathogenic variants should be taken into consideration when investigating patients with unexplained early-onset hyperkinetic movement disorders and neurodevelopmental delay.

Palavras Chave

GNAO1 Encephalopathy; Neurodevelopmental Disorder; Involuntary Movements; Neurogenetic

Área

Neurogenética