title: A congenital myopathy with diaphragmatic weakness not linked to the SMARD1 locus.
abstract: Severe diaphragmatic weakness in infancy is rare. Common causes include structural myopathies, neuromuscular transmission defects, or anterior horn cell dysfunction (spinal muscular atrophy with respiratory distress, SMARD1). We describe a form of infantile diaphragmatic weakness without mutations in the SMARD1 gene, in which pathological and clinical features differ from known conditions, and investigations suggest a myopathy. We identified seven cases in four families. All presented soon after birth with feeding and breathing difficulties, marked head lag, facial weakness, and preserved antigravity movements in the limbs, with arms weaker than legs. All had paradoxical breathing and paralysis of at least one hemi-diaphragm. All required gastrostomy feeding, and all became ventilator-dependent. Investigations included myopathic EMG, muscle biopsy showing myopathic changes, normal electrophysiology and no mutations in SMN1 or IGHMBP2. These seven infants are affected by a myopathic condition clinically resembling SMARD1. However, its pathogenesis appears to be a myopathy affecting predominantly the diaphragm.
authors.affiliation: Dubowitz Neuromuscular Centre, Department of Pediatrics, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 ONN, UK.
authors.forename: L
authors.initials: L
authors.lastname: Hartley
authors.forename: M
authors.initials: M
authors.lastname: Kinali
authors.forename: R
authors.initials: R
authors.lastname: Knight
authors.forename: E
authors.initials: E
authors.lastname: Mercuri
authors.forename: C
authors.initials: C
authors.lastname: Hubner
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.forename: A Y
authors.initials: AY
authors.lastname: Manzur
authors.forename: C
authors.initials: C
authors.lastname: Jimenez-Mallebrera
authors.forename: C A
authors.initials: CA
authors.lastname: Sewry
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D003402:Creatine Kinase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D003964:Diaphragm / Q000503:physiopathology*; D004576:Electromyography; D004750:Enteral Nutrition; D005121:Extremities / Q000503:physiopathology; D005152:Facial Muscles / Q000503:physiopathology; D005260:Female; D006128:Growth / Q000502:physiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009068:Movement / Q000502:physiology; D018908:Muscle Weakness / Q000151:congenital* / Q000235:genetics* / Q000503:physiopathology; D009135:Muscular Diseases / Q000151:congenital* / Q000235:genetics* / Q000503:physiopathology; D012121:Respiration, Artificial; D015656:Respiratory Mechanics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C489892:IGHMBP2 protein, human; D014157:Transcription Factors; D003402:Creatine Kinase