title: Spinal muscular atrophy: clinical spectrum and genetic mutations in Pakistani children.
abstract: BACKGROUND
  In Pakistan the rate of consanguineous marriages is high, thus, the chance of incidence of autosomal recessive disorders is likely to be high. The aim of this study is to investigate the clinical characteristics and genetics of spinal muscular atrophy (SMA) in children who presented to Aga Khan University, Karachi.
  
  
  METHODS
  This study was a retrospective review of the medical charts of children (neonate: 15 years) with discharge diagnosis of SMA during last 10 years. Demographic features, consanguinity, and diagnostic analysis (including genetic analysis) were noted.
  
  
  RESULTS
  During the study period 67 children had a discharge diagnosis of SMA. Werdnig Hoffman disease (SMA type I) was the commonest variant seen in 37 (56%) children. Overall 68% were infants. High parental consanguinity was observed in 68% of the study cohort. The history of delayed development and undiagnosed early death was observed in the families of 19 children. Genetic testing was performed in 22 (33%) children. Survival motor neuron (SMN) 1 gene deletion was found in 19 (86%) of the 22 patients in whom the gene analysis was done and 13 (68%) were also positive for neuronal apoptosis inhibitory proteins (NAIP) deletion.
  
  
  CONCLUSIONS
  SMA is not an uncommon neurodegenerative disorder in Pakistan and SMA type I was the most common type. SMN1 gene deletion was the most common genetic deletion found in this study. In addition, family history of developmental delay and frequent early deaths highlights the need for implementation of prenatal diagnosis for early detection, effective control, and management of this disorder in Pakistan.
authors: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan. shahnaz.ibrahim@aku.edu
authors: Shahnaz
authors: S
authors: Ibrahim
authors: Tariq
authors: T
authors: Moatter
authors: Ali Faisal
authors: AF
authors: Saleem
mesh_terms: D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D003431:Cross-Cultural Comparison; D004252:DNA Mutational Analysis; D004576:Electromyography; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics*; D009431:Neural Conduction / Q000502:physiology; D010154:Pakistan; D012189:Retrospective Studies; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*
chemical_list: C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein