Objective: 0

Background: Introduction: YY1 disease-causing variants are responsible for Grabiele-de-Vries syndrome, an autosomal dominant condition characterized by psychomotor developmental (PD) delay, cognitive impairment, facial dysmorphism and, in some cases, a complex movement disorder. We describe a patient with isolated dystonia with severe oromandibular involvement (OM) due to YY1 haploinsufficiency.

Method: 0

Results: Case Report: The 38-year-old female patient is the first child of healthy nonconsanguineous parents. Patient’s pregnancy and PD were uneventful. The first symptom, a writer´s cramp, appeared when she was 8, although at 3 years old an abnormal body posture motivated orthopaedic evaluation. Dystonia later involved other body parts: right upper limb at the age of 10; right lower limb, laryngeal and OM dystonia at 12; with tongue protrusion induced by speech at 17 years old. She had not facial dysmorphisms and neuropsychological evaluation identified minor executive dysfunction. An extensive diagnostic workup was done, all normal or negative, namely brain MRI, metabolic screening, mitochondrial DNA sequencing, and single-gene Sanger sequencing of TOR1A, THAP1, PANK2 and ATM. Oral medication for dystonia (anticholinergics, levodopa and baclofen) did not show any clinical benefit. OM dystonia had a slight improvement with botulinum toxin. At 30 years old, she was treated with deep brain stimulation (DBS) in globus pallidus internus, with significant improvement in the Fahn-Marsden Scale-motor and -disabling scores (peak improvement of 38,3% and 38,5%, respectively). Nowadays, 9 years after GPi-DBS, the continuous slowly progression of the disease is evident. At age of 38, a next-generation sequencing-based gene panel, including 250 genes associated with dystonia identified a pathogenic, heterozygous variant in YY1 (c.1099dup; p. (Asp367Glyfs*25)).

Conclusion: Conclusion: This patient´s phenotype does not correlate with others previously reported, contributing to the expansion of the YY1phenotype. Interestingly, although most of the reported clinical features of Grabiele-de-Vries syndrome are not present, our patient´s features highly resembles a DYT-THAP1 phenotype, which we hypothesize could be due a negative effect of YY1 loss of function variants on THAP1 transcription, as this two genes closely interact in the oligodendrocyte maturation process. Also, we highlight that YY1-dystonia may respond well to DBS.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-case-of-yy1-related-isolated-dystonia-with-severe-oromandibular-involvement/