Restless Legs Syndrome, Rapid Eye Movement Sleep Behavior Disorder, and Hypersomnia in Patients with Two Parkin Mutations Nade `ge Limousin, MD, 1 Eric Konofal, MD, PhD, 1 Elias Karroum, MD, 1 Ebba Lohmann, MD, 2 Ioannis Theodorou, MD, PhD, 3 Alexandra Du ¨rr, MD, PhD, 2,4 and Isabelle Arnulf, MD, PhD 1 * 1 Unite´des Pathologies du sommeil and UMR 975, Universite´Paris 6, Ho ˆpital Pitie´-Salpe ˆtrie `re, Assistance Publique Ho ˆ pitaux de, Paris, France 2 INSERM UMR S679, Neurologie et The´rapeutique Expe´rimentale, Paris, France 3 Laboratoire d’Immunologie cellulaire et tissulaire, Ho ˆpital Pitie´-Salpe ˆtrie `re, Paris, France 4 De ´partement de Ge´ne´tique et Cytoge´ne´tique, Ho ˆpital Pitie´-Salpe ˆtrie `re, Paris, France Abstract: Parkin gene mutations cause a juvenile parkin- sonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied. The aim of this study was to evaluate the sleep-wake phenotype in patients with two parkin mutations, compared with patients with idiopathic Parkinson’s disease (iPD). Sleep interview and overnight video-polysomnogra- phy, followed by multiple sleep latency tests, were assessed in 11 consecutive patients with two parkin mutations (aged 35–60 years, from seven families) and 11 sex-matched patients with iPD (aged 51–65 years). Sleep complaints in the parkin group included insomnia (73% patients versus 45% in the iPD group), restless legs syndrome (45%, versus none in the iPD group, P 5 0.04), and daytime sleepiness (45%, versus 54% in the iPD group). Of the parkin patients, 45% had REM sleep without atonia, but only 9% had a definite REM sleep behavior disorder. All sleep meas- ures were similar in the parkin and iPD groups. Two parkin siblings had a central hypersomnia, characterized by mean daytime sleep latencies of 3 min, no sleep onset REM peri- ods, and normal nighttime sleep. Although the patients with two parkin mutations were young, their sleep phenotype paralleled the clinical and polygraphic sleep recording abnormalities reported in iPD, except that restless legs syndrome was more prevalent and secondary narcolepsy was absent. Ó 2007 Movement Disorder Society Key words: Parkinson’s disease; hypersomnia; restless legs syndrome; inborn genetic diseases; REM sleep behavior disorder Parkinsonism associated with parkin gene mutations is an autosomal recessive disorder causing a juvenile parkinsonism. 1 Compared with idiopathic Parkinson’s disease (iPD), the parkinsonism associated with parkin gene mutations is characterized by an onset before 45 years of age, more frequent dystonia, symmetric signs at onset, hyperreflexia, and a slow rate of pro- gression. 2,3 Patients also have a good motor response to small doses of levodopa (L-dopa), but they more commonly develop L-dopa-induced dyskinesia and motor fluctuations. 2,3 At least 100 different missense, nonsense, and frameshift point mutations, exon deletions, duplications, and triplications, as well as mutations in the promoter region, have been found in the parkin gene, which is located on chromosome 6q25.2-27.3. 1,3,4 The brain pathology of the parkinson- ism associated with parkin gene mutations is distinct from that of iPD. There is no alphasynuclein deposit in the neurons, and the cell loss and gliosis are restricted Potential conflict of interest: All authors report no financial disclo- sure related to the research covered in the article. This was not an industry-supported study. Additional Supporting Information may be found in the online version of this article. *Correspondence to: Dr. Isabelle Arnulf; Unite ´ des Pathologies du Sommeil, Ho ˆpital Pitie ´-Salpe ˆtrie `re, 47-83 boulevard de l’Ho ˆpital, 75651 Paris Cedex 13, France. E-mail: isabelle.arnulf@psl.aphp.fr Received 20 January 2009; Revised 30 June 2009; Accepted 5 July 2009 Published online 11 August 2009 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.22711 1970 Movement Disorders Vol. 24, No. 13, 2009, pp. 1970–1976 Ó 2009 Movement Disorder Society