Neuropsychiatric and sleep study in autosomal dominant dopa-responsive dystonia

Although the diurnal fluctuation of motor dysfunction, reversible with small doses of dopamine, is a cornerstone for the phenotype of the autosomal dominant Segawa syndrome, the non-motor symptoms of this neurotransmitter deficiency have still received limited attention. This study aims to evaluate...

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Bibliographic Details
Published in:	Molecular genetics and metabolism reports Vol. 31; p. 100870
Main Authors:	Alves Júnior, Ailton C., Daker, Maurício V., Machado, Alexei M.C., Luna, Alan S., Valladares Neto, Dirceu C., Valadares, Eugenia R.
Format:	Journal Article
Language:	English
Published:	Elsevier Inc 01-06-2022 Elsevier
Subjects:	Autosomal dominant familial dystonia Autosomal dominant GPCH1 deficiency Dystonia, Dopa-responsive Dystonic disorders Mental disorders Research Paper Sleep-wake disorders ADHD CHD Mental disorders Autosomal dominant GPCH1 deficiency HGNC 4193 DYT5a WMT-2 MDE Dystonia, Dopa-responsive Sleep-wake disorders SG GTP Cyclohydrolase-1 BDI-II MINI/MINI PLUS WHOQOL-BREF DYT/PARK-GCH1 NSG ESS GCH1 Autosomal dominant familial dystonia GAD MDE PAST BH4 Dystonic disorders NMS L-Dopa DRD PSQI
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Summary:	Although the diurnal fluctuation of motor dysfunction, reversible with small doses of dopamine, is a cornerstone for the phenotype of the autosomal dominant Segawa syndrome, the non-motor symptoms of this neurotransmitter deficiency have still received limited attention. This study aims to evaluate non-motor symptoms of this dopa-responsive dystonia through an intrafamilial comparative cross-sectional study. Seventeen individuals with a c.IVS5 + 3insT (c.626 + 3insT) variation in the GTP cyclohydrolase-1 gene (GCH1, HGNC: 4193) and 34 intrafamilial controls were studied using the Beck Depression Inventory-II, the Wiener Matrizen Test 2, the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the MINI/MINI PLUS Questionnaires, the World Health Organization Quality of Life – BREF Instrument and a drug use assessment questionnaire. No significant difference was found between the groups in the prevalence of sleep disorders and in cognitive function. Nevertheless, generalized anxiety disorder (p = 0.050) and attention-deficit/hyperactivity disorder in childhood (p = 0.011) were observed only in individuals without the molecular variation. The group with the GCH1 variation presented a worse perception about how safe they feel in their daily lives (p = 0.034), less satisfaction with themselves (p = 0.049) and with their relationships (p = 0.029), and a higher prevalence of past major depressive episodes before use of L-Dopa (p = 0.046). Low dopamine could have been protective against generalized anxiety disorder and attention-deficit/hyperactivity disorder in childhood in Segawa group individuals. The prevalence of depression was higher in individuals with the molecular variant prior to the L-Dopa treatment. Considering it, the penetrance estimates for the variant carriers increased from 58.8% to up to 88% in this large studied family. Additionally, neuropsychiatric tests of all individuals with a molecular diagnosis in an affected family are a valuable instrument for its clinical management. •Depression can be a non-motor symptom of autosomal dominant DYT/PARK-GCH1.•Variable expressivity and penetrance can be considered high in this syndrome.•Relatives without dystonia should also be investigated for the genetic variation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2214-4269 2214-4269
DOI:	10.1016/j.ymgmr.2022.100870