title: Prominent scapulae mimicking an inherited myopathy expands the phenotype of CHD7-related disease.
abstract: CHD7 variants are a well-established cause of CHARGE syndrome, a disabling multi-system malformation disorder that is often associated with deafness, visual impairment and intellectual disability. Less severe forms of CHD7-related disease are known to exist, but the full spectrum of phenotypes remains uncertain. We identified a de novo missense variant in CHD7 in a family presenting with musculoskeletal abnormalities as the main manifestation of CHD7-related disease, representing a new phenotype. The proband presented with prominent scapulae, mild shoulder girdle weakness and only subtle dysmorphic features. Investigation revealed hypoplasia of the trapezius and sternocleidomastoid muscles and semicircular canal defects, but he did not fulfill diagnostic criteria for CHARGE syndrome. Although the shoulders are often sloping and anteverted in CHARGE syndrome, the underlying neuromuscular cause has never been investigated. This report expands the phenotypes associated with CHD7 mutations to include a musculoskeletal presentation, with hypoplasia of the shoulder and neck muscles. CHD7 should be considered in patients presenting in childhood with stable scapular winging, particularly if accompanied by dysmorphic features and balance difficulties.
authors.affiliation: Institute for Neuroscience and Muscle Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.|Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Gina L
authors.initials: GL
authors.lastname: O'Grady
authors.affiliation: Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.|Department of Clinical Genetics, Nepean Hospital, Sydney, New South Wales, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Ma
authors.affiliation: Department of Pediatrics, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Deborah
authors.initials: D
authors.lastname: Sival
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Monica T Y
authors.initials: MT
authors.lastname: Wong
authors.affiliation: Medical Imaging, Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Peduto
authors.affiliation: Institute for Neuroscience and Muscle Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.|Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Manoj P
authors.initials: MP
authors.lastname: Menezes
authors.affiliation: Institute for Neuroscience and Muscle Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Young
authors.affiliation: Institute for Neuroscience and Muscle Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Leigh
authors.initials: L
authors.lastname: Waddell
authors.affiliation: Institute for Neuroscience and Muscle Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.|Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Roula
authors.initials: R
authors.lastname: Ghaoui
authors.affiliation: Department of Neurology, Fiona Stanley Hospital, Murdoch, Perth, Western Australia, Australia.|Institute of Immunology and Infectious diseases, Murdoch University, Perth, Western Australia, Australia.
authors.forename: Merrilee
authors.initials: M
authors.lastname: Needham
authors.affiliation: Institute for Neuroscience and Muscle Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.|Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.|Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.|Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: Monkol
authors.initials: M
authors.lastname: Lek
authors.affiliation: Institute for Neuroscience and Muscle Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.|Murdoch Children's Research Institute, Melbourne, Victoria, Australia.|Department of Paediatrics, Faculty of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: North
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.|Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: MacArthur
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Conny Ma
authors.initials: CM
authors.lastname: van Ravenswaaij-Arts
authors.affiliation: Institute for Neuroscience and Muscle Research, Kids Research Institute, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.|Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Nigel F
authors.initials: NF
authors.lastname: Clarke
mesh_terms: D000328:Adult; D058747:CHARGE Syndrome / Q000175:diagnosis / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009139:Musculoskeletal Abnormalities / Q000175:diagnosis / Q000235:genetics*; D020125:Mutation, Missense; D009334:Neck Muscles / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D012540:Scapula / Q000002:abnormalities*
chemical_list: D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human
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