| Title: |
Cardiac Genetic Investigation of Sudden Infant and Early Childhood Death: A Study From Victims to Families |
| Authors: |
Kotta M. -C.; Torchio M.; Bayliss P.; Cohen M. C.; Quarrell O.; Wheeldon N.; Marton T.; Gentilini D.; Crotti L.; Coombs R. C.; Schwartz P. J. |
| Contributors: |
Kotta, M; Torchio, M; Bayliss, P; Cohen, M; Quarrell, O; Wheeldon, N; Marton, T; Gentilini, D; Crotti, L; Coombs, R; Schwartz, P |
| Publisher Information: |
American Heart Association Inc.; US |
| Publication Year: |
2023 |
| Collection: |
Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive) |
| Subject Terms: |
channelopathie; molecular autopsy; sudden infant death syndrome; sudden unexplained death in childhood |
| Description: |
BACKGROUND: Sudden infant death syndrome (SIDS) is the leading cause of death up to age 1. Sudden unexplained death in childhood (SUDC) is similar but affects mostly toddlers aged 1 to 4. SUDC is rarer than SIDS, and although cardiogenetic testing (molecular autopsy) identifies an underlying cause in a fraction of SIDS, less is known about SUDC. METHODS AND RESULTS: Seventy-seven SIDS and 16 SUDC cases underwent molecular autopsy with 25 definitive-evidence arrhythmia-associated genes. In 18 cases, another 76 genes with varying degrees of evidence were analyzed. Parents were offered cascade screening. Double-blind review of clinical-genetic data established genotype– phenotype correlations. The yield of likely pathogenic variants in the 25 genes was higher in SUDC than in SIDS (18.8% [3/16] versus 2.6% [2/77], respec-tively; P=0.03), whereas novel/ultra-rare variants of uncertain significance were comparably represented. Rare variants of uncertain significance and likely benign variants were found only in SIDS. In cases with expanded analyses, likely pathogenic/ likely benign variants stemmed only from definitive-evidence genes, whereas all other genes contributed only variants of uncertain significance. Among 24 parents screened, variant status and phenotype largely agreed, and 3 cases positively cor-related for cardiac channelopathies. Genotype– phenotype correlations significantly aided variant adjudication. CONCLUSIONS: Genetic yield is higher in SUDC than in SIDS although, in both, it is contributed only by definitive-evidence genes. SIDS/SUDC cascade family screening facilitates establishment or dismissal of a diagnosis through definitive variant adjudication indicating that anonymity is no longer justifiable. Channelopathies may underlie a relevant fraction of SUDC. Binary classifications of genetic causality (pathogenic versus benign) could not always be adequate. |
| Document Type: |
article in journal/newspaper |
| File Description: |
ELETTRONICO |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/37589201; info:eu-repo/semantics/altIdentifier/wos/WOS:001062730000046; volume:12; issue:17; journal:JOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE; https://hdl.handle.net/10281/467703 |
| DOI: |
10.1161/JAHA.122.029100 |
| Availability: |
https://hdl.handle.net/10281/467703; https://doi.org/10.1161/JAHA.122.029100 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative Commons ; license uri:http://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.5D9A5ACF |
| Database: |
BASE |