title: Genetic testing in children with surfactant dysfunction.
abstract: OBJECTIVE
  To present the UK experience in genetic diagnoses of surfactant protein dysfunction disorders and develop a referral algorithm for neonates and children with persistent respiratory problems.
  
  
  METHODS
  Between 2006 and 2011, 427 cases were referred for surfactant mutation analyses to the North East Thames Regional Molecular Genetics Laboratory at Great Ormond Street Hospital, London. The results were reviewed and referring physicians of mutation positive cases contacted to complete a questionnaire providing clinical, radiological, histological and outcome information.
  
  
  RESULTS
  25 new cases were found to have genetic mutations for surfactant dysfunction disorders (7.5%), with six resulting in surfactant protein B dysfunction, seven surfactant protein C dysfunction and 12 ATP-binding cassette subfamily A member 3 (ABCA3) dysfunction. The referrals were from 15 different paediatric centres. In addition, three affected surfactant protein B (SFTPB) cases were prenatal diagnoses, following the birth of previously affected children. The majority of the confirmed cases (23 of 25) were born after 37 weeks gestation. All children with SFTPB dysfunction and the majority of ABCA3 patients presented with respiratory distress at birth. All SFTPB cases died from intractable respiratory failure. The outcome for ABCA3 mutations was variable with seven survivors. The clinical and radiological presentation of surfactant protein C (SFTPC) patients suggested mainly interstitial lung process with the majority surviving on medication.
  
  
  CONCLUSIONS
  Surfactant mutation analysis is now well established in the UK and allows better genetic diagnosis and counselling. The rarity of the condition makes it difficult to develop a validated algorithm for genetic evaluation with a need for international networking. Referrals need to be rationalised for the service to be time and cost effective.
authors.affiliation: Department of Pediatric Intensive Care, Great Ormond Street Hospital, London, UK.
authors.forename: Simona
authors.initials: S
authors.lastname: Turcu
authors.forename: Emma
authors.initials: E
authors.lastname: Ashton
authors.forename: Lucy
authors.initials: L
authors.lastname: Jenkins
authors.forename: Atul
authors.initials: A
authors.lastname: Gupta
authors.forename: Quen
authors.initials: Q
authors.lastname: Mok
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008131:London; D008168:Lung / Q000503:physiopathology*; D008171:Lung Diseases / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics*; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics*
chemical_list: D018528:ATP-Binding Cassette Transporters; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C
keywords: genetic testing; paediatric lung disease; surfactant dysfunction