title: SIL1-related Marinesco-Sjoegren syndrome (MSS) with associated motor neuronopathy and bradykinetic movement disorder.
abstract: Marinesco-Sjoegren syndrome (MSS) is a recessively inherited multisystem disorder caused by mutations in SIL1 and characterized by cerebellar atrophy with ataxia, cataracts, a skeletal muscle myopathy, and variable degrees of developmental delay. Pathogenic mechanisms implicated to date include mitochondrial, nuclear envelope and lysosomal-autophagic pathway abnormalities. Here we present a 5-year-old girl with SIL1-related MSS and additional unusual features of an associated motor neuronopathy and a bradykinetic movement disorder preceding the onset of ataxia. These findings suggest that an associated motor neuronopathy may be part of the phenotypical spectrum of SIL1-related MSS and should be actively investigated in genetically confirmed cases. The additional observation of a bradykinetic movement disorder suggests an intriguing continuum between neurodevelopmental and neurodegenerative multisystem disorders intricately linked in the same cellular pathways.
authors.affiliation: Department of Paediatric Neurology, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Byrne
authors.affiliation: Department of Paediatric Neurology, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK.
authors.forename: Nomazulu
authors.initials: N
authors.lastname: Dlamini
authors.affiliation: Department of Paediatric Neurology, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lumsden
authors.affiliation: Department of Neurophysiology, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Pitt
authors.affiliation: Dubowitz Neuromuscular Centre, Institute of Child Health, University College London, London, UK.
authors.forename: Irina
authors.initials: I
authors.lastname: Zaharieva
authors.affiliation: Dubowitz Neuromuscular Centre, Institute of Child Health, University College London, London, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.affiliation: Department of Neuropathology, King's College Hospital, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: King
authors.affiliation: Department of Clinical Genetics, Guy's Hospital, London, UK.
authors.forename: Leema
authors.initials: L
authors.lastname: Robert
authors.affiliation: Department of Paediatric Neurology, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, UK; Randall Division for Cell and Molecular Biophysics, Muscle Signalling Section, King's College, London, UK; Department of Basic and Clinical Neuroscience Division, IoPPN, King's College, London, UK. Electronic address: Heinz.Jungbluth@gstt.nhs.uk.
authors.forename: Heinz
authors.initials: H
authors.lastname: Jungbluth
mesh_terms: D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D005145:Face / Q000473:pathology; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D018476:Hypokinesia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C418483:SIL1 protein, human
keywords: Autophagy; Bradykinetic movement disorder; Marinesco–Sjoegren syndrome (MSS); Motor neuronopathy; Multisystem disorders; SIL1 gene