A De Rosa1, T Pellegrino2, S Pappatà2, M Lieto3, V Bonifati4, V Palma5, A Topa3, L Santoro3, L Bilo3, A Cuocolo6, G De Michele7. 1. Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy. Electronic address: anna.derosa1@unina.it. 2. Institute of Biostructure and Bioimaging, National Council of Research, Naples, Italy. 3. Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy. 4. Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands. 5. Department of Neurophysiology, San Gennaro Hospital, Naples, Italy. 6. Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. 7. Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy; Institute of Biostructure and Bioimaging, National Council of Research, Naples, Italy.
Abstract
INTRODUCTION: PARK20 is a rare autosomal recessive parkinsonism related to the SYNJ1 gene and characterized by early-onset of disease and atypical signs such as supranuclear vertical gaze palsy, dementia, dystonia, and generalized tonic-clonic seizures. OBJECTIVE: Non-motor features and cardiac sympathetic innervation were assessed in two siblings affected by parkinsonism who harboured the homozygous Arg258Gln mutation in the SYNJ1 gene. METHODS: The Non-Motor Symptoms, the SCOPA-AUT, the Mayo Sleep Questionnaires and polysomnography were used to investigate non-motor signs (NMS), autonomic dysfunction and REM Behavioural Disorder (RBD). Cognitive functions were examined by an extensive battery of neuropsychological tests. In addition, motor and sensory nerve conduction studies and evoked laser potentials were performed. Cardiac sympathetic innervation was assessed in the two patients by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, computing early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR). RESULTS: Among the non-motor symptoms and autonomic signs, case 1 had cold intolerance, drooling and dysphagia, while case 2 had pain and urinary dysfunction. Both cases showed mood and behavioural disorders. RBD were not found, whereas the neuropsychological assessment revealed a progressive cognitive impairment. Neurophysiological studies revealed no abnormalities. Indexes of cardiac sympathetic innervation in the two patients did not differ from those of control subjects. CONCLUSIONS: Our findings expand the phenotypic profile of SYNJ1-related parkinsonism. Preserved cardiac sympathetic function and absence of RBD suggest that PARK20 should be explained by a pathogenic mechanism different from Lewy Body pathology, or that the latter is not as widespread as idiopathic Parkinson's disease.
INTRODUCTION:PARK20 is a rare autosomal recessive parkinsonism related to the SYNJ1 gene and characterized by early-onset of disease and atypical signs such as supranuclear vertical gaze palsy, dementia, dystonia, and generalized tonic-clonic seizures. OBJECTIVE: Non-motor features and cardiac sympathetic innervation were assessed in two siblings affected by parkinsonism who harboured the homozygous Arg258Gln mutation in the SYNJ1 gene. METHODS: The Non-Motor Symptoms, the SCOPA-AUT, the Mayo Sleep Questionnaires and polysomnography were used to investigate non-motor signs (NMS), autonomic dysfunction and REM Behavioural Disorder (RBD). Cognitive functions were examined by an extensive battery of neuropsychological tests. In addition, motor and sensory nerve conduction studies and evoked laser potentials were performed. Cardiac sympathetic innervation was assessed in the two patients by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, computing early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR). RESULTS: Among the non-motor symptoms and autonomic signs, case 1 had cold intolerance, drooling and dysphagia, while case 2 had pain and urinary dysfunction. Both cases showed mood and behavioural disorders. RBD were not found, whereas the neuropsychological assessment revealed a progressive cognitive impairment. Neurophysiological studies revealed no abnormalities. Indexes of cardiac sympathetic innervation in the two patients did not differ from those of control subjects. CONCLUSIONS: Our findings expand the phenotypic profile of SYNJ1-related parkinsonism. Preserved cardiac sympathetic function and absence of RBD suggest that PARK20 should be explained by a pathogenic mechanism different from Lewy Body pathology, or that the latter is not as widespread as idiopathic Parkinson's disease.
Authors: Jun Tian; Satya R Vemula; Jianfeng Xiao; Enza Maria Valente; Giovanni Defazio; Simona Petrucci; Angelo Fabio Gigante; Monika Rudzińska-Bar; Zbigniew K Wszolek; Kathleen D Kennelly; Ryan J Uitti; Jay A van Gerpen; Peter Hedera; Elizabeth J Trimble; Mark S LeDoux Journal: Mol Genet Genomic Med Date: 2018-05-16 Impact factor: 2.183