Clinical and polysomnographic features of a large Turkish pedigree with restless leg syndrome and periodic limb movements

Babacan-Yildiz, Gülsen; Gürsoy, Esra Başar; Kolukisa, Mehmet; Karaköse, Fatmanur; Akkoyunlu, Emin M.; Çelebi, Arif; Lohmann, Ebba

doi:10.1007/s11325-012-0756-5

Cited by 3 publications

(2 citation statements)

References 26 publications

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“…Historically, RLS has been categorized as either primary (idiopathic) or secondary. Primary RLS has a strong genetic component, with family pedigree reports indicating a predominantly autosomal dominant pattern of inheritance, often with variable expressivity [42][43][44][45][46][47][48]. When giving a family history, 50 to 60% of iRLS patients report a first-degree relative with RLS symptoms [36,49] with evidence from another study indicating a heritability of 54% [50].…”

Section: Clinical Presentation and Diagnosismentioning

confidence: 99%

Restless Legs Syndrome: Contemporary Diagnosis and Treatment

et al. 2021

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Restless legs syndrome (RLS) is characterized by an uncomfortable urge to move the legs while at rest, relief upon movement or getting up to walk, and worsened symptom severity at night. RLS may be primary (idiopathic) or secondary to pregnancy or a variety of systemic disorders, especially iron deficiency, and chronic renal insufficiency. Genetic predisposition with a family history is common. The pathogenesis of RLS remains unclear but is likely to involve central nervous system dopaminergic dysfunction, as well as other, undefined contributing mechanisms. Evaluation begins with a thorough history and examination, and iron measures, including ferritin and transferrin saturation, should be checked at presentation and with worsened symptoms, especially when augmentation develops. Augmentation is characterized by more intense symptom severity, earlier symptom occurrence, and often, symptom spread from the legs to the arms or other body regions. Some people with RLS have adequate symptom control with non-pharmacological measures such as massage or temperate baths. First-line management options include iron-replacement therapy in those with evidence for reduced body-iron stores or, alternatively, with prescribed gabapentin or pregabalin, and dopamine agonists such as pramipexole, ropinirole, and rotigotine. Second-line therapies include intravenous iron infusion in those who are intolerant of oral iron and/or those having augmentation with intense, severe RLS symptoms, and opioids including tramadol, oxycodone, and methadone. RLS significantly impacts patients' quality of life and remains a therapeutic area sorely in need of innovation and a further pipeline of new, biologically informed therapies. KeywordsRestless legs syndrome • Periodic limb movement disorder • Periodic leg movements • Cardiovascular risk • Treatment • Dopamine agonist • Alpha-2-delta ligand • Opiate • Iron deficiency.

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Section: Clinical Presentation and Diagnosismentioning

confidence: 99%

Restless Legs Syndrome: Contemporary Diagnosis and Treatment

et al. 2021

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“…Family aggregation is one of the features of RLS occurrence [6], 40.9% -92.0% of RLS patients have a family history [10,11], in accordance with autosomal dominant (AD) inheritance [12]. Although genetic variation has been proven to be associated with the occurrence of RLS, such as BTBD9, MEIS1, MAP2K5/SKOR1, MAP2K5/LBXCOR1, and PTPRD [13][14][15][16][17], the key genetic variants have not been identi ed.…”

Section: Introductionmentioning

confidence: 99%

Novel FTA2 variants were observed in patients with restless legs syndrome via whole-exome sequencing

Li,

Zhang,

Zhang

et al. 2024

Preprint

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Background: Restless legs syndrome (RLS) is often characterized by familial aggregation. Molecular genetic changes are closely related to the occurrence of the disease, but the key gene variations are unclear. Here, genetic changes were investigated in an RLS family. Methods: 4 ml EDTA anticoagulant peripheral blood was collected from patients in a family with RLS, and genomic DNA was extracted. Whole-exome sequencing (WES) was performed by the Illumina platform, and variants were distinguished by GATK haplotype caller software. Polyphen-2 and SIFT tools were used to analyze the effect of missense mutations on protein structure and function, and the HSF tool was used to analyze the effect of variants on splicing defects. Results: Based on the RLS diagnostic criteria, 4 individuals were diagnosed with RLS in this family. Among them, three subjects underwent a WES examination, and two novel FAT2 variants were detected in all subjects: exon 6:c.4174g > A, p.Asp1392Asn and intron 19: c.11464-8C > G. The frequency of these two variants was extremely rare in the normal population database. Polyphen2 tool analysis results suggested c.4174G> A, p.Asp1392Asn, was identified as probably damaging with a 0.910 score (sensitivity: 0.69; specificity: 0.90); SIFT tool predicts that its risk factor score is −1.510 (＞ 2.5), which is considered neutral damage. For intron19: c.11464-8C > G,, although mutation occurred in the late intron position, no obvious splicing sequence change was predicted by the HSF software. Conclusion: Two novel FAT2 variants were identified in three patients from an RLS family, of which exon 6: c.4174G > A was likely to damage protein function.

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