Sudden death in young people (Version 1.15)

Description

Eligibility statement for Unexplained sudden death in the young (38566):

Unexplained sudden death in the young inclusion criteria (38569)
•	Sudden death at age less than or equal to 40 (including Sudden Infant Death Syndrome), AND
•	No diagnosis established on post mortem examination, AND
•	Absence of a pre-existing condition to explain the death.
•	Parents should be recruited under this category in paediatric cases if available
•	In adult cases the deceased individual should be recruited as a singleton; if surviving relatives have a phenotype which points to a particular condition, they should be the focus of further investigation or recruitment to the programme. 
•	Surviving relatives must be available to provide appropriate consent.

Unexplained sudden death in the young exclusion criteria (38569)
•	Death in the context of a known diagnosed disease or accident
•	Cause of death determined by post mortem examination
•	No post mortem examination carried out
•	No DNA or frozen tissue stored at post mortem.

Prior genetic testing guidance (38569)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Unexplained sudden death in the young prior genetic testing genes (38569)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 No genes listed

Closing statement (38569)
These requirements will be kept under continual review during the main programme and may be subject to change.

Rules for application of gene panels:

For patients equal to or under the age of 18 months, the following panels will also be applied:
• All metabolic panels
• Mitochondrial disorders

For all patients the following panels will also be applied:
• Long QT syndrome
• Arrhythmogenic Right Ventricular Cardiomyopathy
• Brugada Syndrome
• Hypertrophic Cardiomyopathy
• Catecholaminergic Polymorphic Ventricular Tachycardia
• Left Ventricular Noncompaction Cardiomyopathy
• Dilated cardiomyopathy

Note that the 'Familial Thoracic Aortic Aneurysm Disease' panel will not be applied, as these disorders or defects (including Loeys Dietz syndromes and Marfan Syndrome) should be identified during a post-mortem examination.

The 'Sudden death in young people' panel does not include genes that are green on one of the additional cardiac panels listed above. This panel also does not include genes associated with disorders or defects that would be identified in a post mortem examination.

Panel Activity

8 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
Bill Newman (Manchester Centre for Genomic Medicine)

Group: other
Workplace: other
Richard Scott (Genomics England Curator)

Group: Other
Workplace: Other
Ellen Thomas (Genomics England Curator)

Group: Other
Workplace: Other
Sarah Leigh (Genomics England Curator)

Group: Other
Workplace: Other
Rebecca Foulger (Genomics England curator)

Group: Other
Workplace: Other
Alice Gardham (Genomics England)

Group: Other
Workplace: Other
Eleanor Williams (Genomics England Curator)

Group: Other
Workplace: Other

35 Entities

34 reviewed, 4 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 35 Entitiess
Green Green List (high evidence)	GLRA1	1 review	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Hyperekplexia, hereditary 1, 149400 Tags
Green Green List (high evidence)	PHOX2B	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Emory Genetics Laboratory Expert Review Green Literature Other Radboud University Medical Center, Nijmegen Phenotypes sudden infant death syndrome unclassified sudden infant death USID Congenital Central Hypoventilation Syndrome CCHS Central hypoventilation syndrome, congenital, with or without Hirschsprung disease, 209880 Tags nucleotide-repeat-expansion
Green Green List (high evidence)	PPA2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Literature Phenotypes Unexpected cardiac arrest in infancy Tags
Green Green List (high evidence)	TSPYL1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Other Radboud University Medical Center, Nijmegen Phenotypes Sudden infant death with dysgenesis of the testes syndrome OMIM:608800 sudden infant death-dysgenesis of the testes syndrome MONDO:0012124 Tags founder-effect
Amber Amber List (moderate evidence)	KCNJ8	2 reviews	Unknown	Sources Emory Genetics Laboratory Expert Review Amber Radboud University Medical Center, Nijmegen Phenotypes arrhythmia Sudden infant death syndrome ?Ventricular fibrillation Tags
Red Red List (low evidence)	ASCL1	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Other Phenotypes Central hypoventilation syndrome, congenital, 209880 CCHS Tags
Red Red List (low evidence)	BDNF	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Other Phenotypes Central hypoventilation syndrome, congenital, 209880 CCHS Tags
Red Red List (low evidence)	CACNA2D1	2 reviews	Unknown	Sources Expert Review Red Literature Phenotypes Sudden death cardiac arrhythmia Tags
Red Red List (low evidence)	EDN3	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Other Phenotypes Central hypoventilation syndrome, congenital, 209880 CCHS Tags
Red Red List (low evidence)	GDNF	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Other Phenotypes Central hypoventilation syndrome, 209880 CCHS Tags
Red Red List (low evidence)	KCND2	2 reviews	Unknown	Sources Expert Review Red Other Radboud University Medical Center, Nijmegen Phenotypes J-wave syndrome with sudden cardiac death sudden arrhythmic death sudden cardiac arrest Tags
Red Red List (low evidence)	KCND3	1 review	Unknown	Sources Emory Genetics Laboratory Expert Review Red Other Phenotypes sudden unexplained death arrhythmia sudden cardiac arrest Tags
Red Red List (low evidence)	MAOA	1 review	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Literature Phenotypes sudden infant death syndrome Tags promoter
Red Red List (low evidence)	PPP1R13L	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Literature Phenotypes cardio-cutaneous syndrome sudden cardiac death Tags watchlist
Red Red List (low evidence)	RET	0 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Other Phenotypes Central hypoventilation syndrome, congenital, 209880 CCHS Tags
Red Red List (low evidence)	SLC6A4	1 review	Unknown	Sources Literature Phenotypes Sudden infant death syndrome Tags
No list No list	AARS2	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Removed Illumina TruGenome Clinical Sequencing Services Literature Other Radboud University Medical Center, Nijmegen Phenotypes early infantile cardiac failure infantile mitochondrial cardiomyopathy Combined Oxidative Phosphorylation Deficiency Combined oxidative phosphorylation deficiency 8, 614096 fatal infantile hypertrophic mitochondrial cardiomyopathy Tags curated_removed
No list No list	ACADM	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Removed Literature Phenotypes Medium chain acyl-CoA dehydrogenase deficiency MCADD MCAD deficiency-associated sudden death sudden infant death syndrome SIDS Tags curated_removed
No list No list	AKAP10	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Removed Other Phenotypes {Cardiac conduction defect, susceptibility to}, 115080 increased risk of sudden cardiac death Tags curated_removed
No list No list	AKAP9	1 review	Unknown	Sources Expert Review Removed UKGTN Phenotypes Molecular autopsy Tags curated_removed
No list No list	AQP4	1 review	Unknown	Sources Expert Review Removed Literature Phenotypes sudden infant death syndrome SIDS Tags curated_removed
No list No list	CAV3	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Emory Genetics Laboratory Expert Review Removed Literature Other Phenotypes Cardiomyopathy, familial hypertrophic, 192600 Sudden death sudden death in young subjects Sudden Infant Death Syndrome SIDS Sudden Cardiac Arrest Sudden Infant Death Syndrome Tags curated_removed
No list No list	CTNNA3	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Emory Genetics Laboratory Expert Review Removed Other Phenotypes Arrhythmias Arrhythmogenic right ventricular dysplasia, familial, 13, 615616 Tags curated_removed
No list No list	FEV	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Removed Literature Phenotypes SIDS Sudden infant death syndrome Tags curated_removed
No list No list	IL10	1 review	Unknown	Sources Expert Review Removed Literature Tags curated_removed promoter
No list No list	IL6	1 review	Unknown	Sources Expert Review Removed Literature Tags curated_removed
No list No list	MT-CYB	1 review	MITOCHONDRIAL	Sources Expert Review Removed Other Phenotypes cardiomyopathy infantile histiocytoid, 500000 infantile cardiomyopathy with histiocytoid change cardiac arrest Tags curated_removed
No list No list	MT-ND1	1 review	MITOCHONDRIAL	Sources Expert Review Removed Literature Other Phenotypes Sudden infant death syndrome, 272120 SIDS SIDS sudden infant death syndrome, 272120, Tags curated_removed
No list No list	MT-TL1	1 review	MITOCHONDRIAL	Sources Expert Review Removed Literature Other Phenotypes Sudden infant death syndrome, 272120 SIDS SIDS Tags curated_removed
No list No list	MYLK2	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Removed Other UKGTN Phenotypes Cardiomyopathy, hypertrophic, 1, digenic, 192600 sudden death in young subjects Molecular autopsy Familial Hypertrophic Cardiomyopathy HCM Tags curated_removed
No list No list	NKX2-5	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Removed Other Phenotypes Ventricular septal defect 3, 614432 sudden cardiac death Tags curated_removed
No list No list	RYR2	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Removed UKGTN Phenotypes Arrhythmogenic right ventricular dysplasia 2, 600996 Ventricular tachycardia, catecholaminergic polymorphic, 1, 604772 Tags curated_removed
No list No list	SCN4B	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Removed UKGTN Phenotypes Molecular autopsy Arrhythmia/Cardiac Arrest Long QT syndrome Tags curated_removed
No list No list	SLC25A4	1 review	Not set	Sources Expert Review Removed UKGTN Phenotypes Molecular autopsy Familial Hypertrophic Cardiomyopathy HCM Tags curated_removed
No list No list	TMPO	1 review	Not set	Sources Expert Review Removed UKGTN Phenotypes Molecular autopsy Tags curated_removed

Major version comments

This panel contains genes which aren't arrhythmic or metabolic causes of sudden death with normal post mortem.

Sudden death in young people (Version 1.15)

8 reviewers

35 Entities

34 reviewed, 4 green

1 review

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3 reviews

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2 reviews

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2 reviews

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1 review

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1 review

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2 reviews

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1 review

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1 review

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1 review

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1 review

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2 reviews

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2 reviews

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1 review

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