title: Interfamilial phenotypic heterogeneity in SMARD1.
abstract: Spinal muscular atrophy with respiratory distress (SMARD1: mu-binding protein 2 gene mutation) is characterised by low birth weight, progressive distal limb weakness, diaphragmatic paralysis and subsequent respiratory failure manifesting before 13 months of age. Our case report illustrates marked phenotype variability in two siblings with an identical genetic mutation of SMARD1, one of whom died of fulminant respiratory failure aged 6 months, whereas the other shows limb weakness but, only mild sleep hypoventilation aged 12 years. This suggests other compensatory mechanisms may play a role in modifying SMARD1; broadening our perception of phenotype. Therefore, SMARD1 phenotype should be considered in cases of atypical spinal muscular atrophy even in the absence of overt diaphragmatic weakness.
authors.affiliation: Department of Neurology, Evelina Children's Hospital, Lambeth Palace Road, London SE1 7EH, UK. sonia.joseph@luht.scot.nhs.uk
authors.forename: S
authors.initials: S
authors.lastname: Joseph
authors.forename: S A
authors.initials: SA
authors.lastname: Robb
authors.forename: S
authors.initials: S
authors.lastname: Mohammed
authors.forename: S
authors.initials: S
authors.lastname: Lillis
authors.forename: A
authors.initials: A
authors.lastname: Simonds
authors.forename: A Y
authors.initials: AY
authors.lastname: Manzur
authors.forename: S
authors.initials: S
authors.lastname: Walter
authors.forename: E
authors.initials: E
authors.lastname: Wraige
mesh_terms: D000293:Adolescent; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D017809:Fatal Outcome; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D018908:Muscle Weakness / Q000235:genetics; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012131:Respiratory Insufficiency / Q000235:genetics*; D012133:Respiratory Paralysis / Q000235:genetics; D035781:Siblings; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D005819:Genetic Markers; C489892:IGHMBP2 protein, human; D014157:Transcription Factors