title: Long QT molecular autopsy in sudden infant death syndrome.
abstract: OBJECTIVE
  To describe experience of long QT (LQT) molecular autopsy in sudden infant death syndrome (SIDS).
  
  
  METHODS
  Descriptive audit from two distinct periods: (1) A prospective, population-based series between 2006 and 2008 ('unselected'). (2) Before and after 2006-2008, with testing guided by a cardiac genetic service ('selected'). LQT genes 1, 2, 3, 5, 6 and 7 were sequenced. Next of kin were offered cardiac evaluation.
  
  
  METHODS
  New Zealand.
  
  
  METHODS
  102 SIDS cases.
  
  
  METHODS
  Nil. Main outcome measures Detection of genetic variants.
  
  
  RESULTS
  Maori 49 (47%), and Pacific island 24 (23%), infants were over-represented. Risk factors were common; bed sharing was reported in 49%. Rare genetic variants were commoner within the selected than unselected populations (5 of 31 infants (16%) vs 3 of 71 infants (4%) p < 0.05). In the selected population two infants had variants of definite or probable pathogenicity (KCNQ1, E146K; KCNH2, R1047L), two had novel variants of possible pathogenicity in SCN5A (I795F, F1522Y) and one had R1193Q in SCN5A, of doubtful pathogenicity. R1193Q was also the only variant in the three cases from the unselected population and occurred as a second variant with R1047L. Engaging families proved challenging. Only 3 of 8 (38%) variant-positive cases and 18 of 94 (19%) of variant-negative families participated in cardiac/genetic screening.
  
  
  CONCLUSIONS
  LQT molecular autopsy has a very low diagnostic yield among unselected SIDS cases where risk factors are common. Diagnostic yield can be higher with case selection. Engagement of the family prior to genetic testing is essential to counsel for the possible uncertainty of the results and to permit family genotype-phenotype cosegregation studies.
authors.forename: Joanna Moira
authors.initials: JM
authors.lastname: Glengarry
authors.forename: Jackie
authors.initials: J
authors.lastname: Crawford
authors.forename: Paul Lowell
authors.initials: PL
authors.lastname: Morrow
authors.forename: Simon Robert
authors.initials: SR
authors.lastname: Stables
authors.forename: Donald Roy
authors.initials: DR
authors.lastname: Love
authors.forename: Jonathan Robert
authors.initials: JR
authors.lastname: Skinner
mesh_terms: D001344:Autopsy; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000150:complications / Q000235:genetics* / Q000401:mortality; D008297:Male; D008485:Medical Audit; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics; D009520:New Zealand; D011446:Prospective Studies; D013398:Sudden Infant Death / Q000209:etiology / Q000235:genetics*
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human