Long QT molecular autopsy in sudden infant death syndrome.

Content Provider	Europe PMC
Author	Glengarry, Joanna Moira Crawford, Jackie Morrow, Paul Lowell Stables, Simon Robert Love, Donald Roy Skinner, Jonathan Robert
Copyright Year	2014
Abstract	ObjectiveTo describe experience of long QT (LQT) molecular autopsy in sudden infant death syndrome (SIDS).DesignDescriptive 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.SettingNew Zealand.Patients102 SIDS cases.InterventionsNil.Main outcome measuresDetection of genetic variants.ResultsMaori 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.ConclusionsLQT 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.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC4078670&blobtype=pdf
ISSN	00039888
Journal	Archives of Disease in Childhood [Arch Dis Child]
Volume Number	99
DOI	10.1136/archdischild-2013-305331
PubMed Central reference number	PMC4078670
Issue Number	7
PubMed reference number	24596401
e-ISSN	14682044
Language	English
Publisher	BMJ Publishing Group
Publisher Date	2014-03-04
Publisher Place	BMA House, Tavistock Square, London, WC1H 9JR
Access Restriction	Open
Rights License	This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/ Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions
Subject Keyword	SIDS Genetics long QT Syndrome Molecular Autopsy
Content Type	Text
Resource Type	Article
Subject	Pediatrics, Perinatology and Child Health