Expanding the phenotype of GNAO1 related movement disorders: Two cases with mild phenotypes.

Amal Abu Libdeh,Albert Chang

doi:10.17724/jicna.2020.168

Abstract

Background: Pathogenic variants in the GNAO1 gene have been previously linked to severe epileptic encephalopathy, severe progressive movement disorders, developmental delay, and intellectual disability. Method: report of 2 cases. Results: we present 2 unrelated girls, an 18-year-old, and a 4.5-year-old, with mild phenotypes. While each was noted early on to have hypotonia, failure to thrive, and developmental delay, they both have made significant progress with various therapeutic interventions. Neither have had any developmental regression, seizures or choreoathetosis. Conclusion: these 2 cases further expand the phenotype spectrum of GNAO1 mutations, which is important for counseling and to help guide management plans.

Highlights

Guanine-binding protein (G-protein)-coupled receptors modulate neuronal excitability
The most abundant class of Ga-subunits is called Gao and is encoded by the GNAO1 gene [1]. Variants in this gene have previously been linked to severe epileptic encephalopathy and severe hyperkinetic disorders
Chromosomal microarray was normal, and testing for Rett syndrome and for Prader Willi syndrome were negative. She had exome-sequencing via GeneDx, and that showed the patient to be heterozygous for a de novo pathogenic variant in the GNAO1 gene (C.724-8G>A; IVS68G>A)

Summary

Introduction

Guanine-binding protein (G-protein)-coupled receptors modulate neuronal excitability. At the age of three months, she was noted to have low tone and failure to thrive She has global developmental delay but has been making steady progress with various therapies (physical, occupational and speech). Chromosomal microarray was normal, and testing for Rett syndrome and for Prader Willi syndrome were negative Most recently, she had exome-sequencing via GeneDx, and that showed the patient to be heterozygous for a de novo pathogenic variant in the GNAO1 gene (C.724-8G>A; IVS68G>A). She had exome-sequencing via GeneDx, and that showed the patient to be heterozygous for a de novo pathogenic variant in the GNAO1 gene (C.724-8G>A; IVS68G>A) For this gene, 100% of the coding region was covered at a minimum of 10x. This variant was not observed in large population cohorts [4]

Discussion

Disclosures

Findings

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