Objective: To present a young adolescent female with functional dystonia phenotype progressed to status dystonia/anarthria and mental confusion, even more molecular genetic of family members appeared the pathogenic variant of GNAO1 gene.

Background: GNAO1 dominant variants were first described in 2013 in Japanese infantile as developmental and epileptic encephalopathy 17 (DEE17, OMIM 615473). A different phenotype was later identified as neurodevelopmental disorder with involuntary movements (NEDIM, OMIM 617493). The GNAO1 gene encodes the α-subunit of a guanine nucleotide-binding Go protein (Gαo), crucial for cAMP cascade in the CNS, especially in the cerebellum, hippocampus, and the striatum.

Method: Genetic screening using targeted gene panel sequencing by IonTorrent system was performed. A systematic literature reviews were conducted in the PubMed database to identify published articles including patients with GNAO1 genetic defects from inception to date.

Results: A 22-year-old female presented with adjustment disorders of DSM-V psychiatry disorder, following isolated dystonia of the left hands while walking. She developed decreased visu l acuity, which was alleviated by glucocorticoid administration, which was assumed to be an immune-related neurological disease. After being reprimanded by a senior, she developed several days of confusion, bizarre tightrope walking appeared, torsion dystonia of the trunk and eye deviation abnormalities, which recovered after dopamine infusion. GABA_A SPECT showed a widespread dysregulation of endogenous GABA activities. Gait disorder was alleviated by oral administration of Sulpiride and Haloperidol, over the years progressed to status muteness and catalepsy.

The gene panel sequencing identified a GNAO1 rare variant (c.485G>A, p.R162Q) of the patient, and her mother as unaffected carrier by segregation gene analysis of targeted family members.

According to the review, 312 patients with cardinal single nucleotide variants, different copy number deletion, and rare incomplete penetrance as our GNAO1 family.

Conclusion: This young female functional dystonia underscores the genetic backgrounds, because she appeared intellectually normal development, but the disease progressed over the years to status mute and catalepsy, appear indicative for challenging as hallmark of GNAO1 variants.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/japanese-family-of-dystonia-related-to-gnao1-pathogenic-variant-and-systematic-literature-review/