PT  - JOURNAL ARTICLE
AU  - Glengarry, Joanna Moira
AU  - Crawford, Jackie
AU  - Morrow, Paul Lowell
AU  - Stables, Simon Robert
AU  - Love, Donald Roy
AU  - Skinner, Jonathan Robert
TI  - Long QT molecular autopsy in sudden infant death syndrome
AID  - 10.1136/archdischild-2013-305331
DP  - 2014 Jul 01
TA  - Archives of Disease in Childhood
PG  - 635--640
VI  - 99
IP  - 7
4099  - http://adc.bmj.com/content/99/7/635.short
4100  - http://adc.bmj.com/content/99/7/635.full
SO  - Arch Dis Child2014 Jul 01; 99
AB  - Objective To describe experience of long QT (LQT) molecular autopsy in sudden infant death syndrome (SIDS). Design 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. Setting New Zealand. Patients 102 SIDS cases. Interventions 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.