Extreme early-onset hypertension (Version 1.21)

Description

Extreme early-onset hypertension inclusion criteria
- Hypertension (defined in adults by blood pressure > 160/100 in clinic AND average BP of 150/95 on ambulatory blood pressure monitoring) occurring below the age of 30.

Extreme early-onset hypertension exclusion criteria
- Primary hyperaldosteronism, phaeochromocytoma, Cushing's syndrome and hyper/hypothyroidism

Prior genetic testing guidance
- 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.

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

Panel Activity

9 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
John Sayer (Newcastle University)

Group: GeCIP domain
Workplace: NHS clinical service
Patricia Munroe (Queen Mary University of London)

Group: GeCIP domain
Workplace: Research lab
Fiona Karet (Universit y of Cambridge)

Group: GeCIP domain
Workplace: NHS clinical service
Sarah Leigh (Genomics England Curator)

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

Group: Other
Workplace: Other
Ivone Leong (Genomics England Curator)

Group: Other
Workplace: Other
Arina Puzriakova (Genomics England Curator)

Group: Other
Workplace: Other
Achchuthan Shanmugasundram (Genomics England Curator)

Group: Other
Workplace: Other

27 Entities

27 reviewed, 15 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 27 Entitiess
Green Green List (high evidence)	CUL3	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes Pseudohypoaldosteronism, type IIE, 614496 Tags
Green Green List (high evidence)	CYP11B1	3 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Aldosteronism, glucocorticoid-remediable, OMIM:103900 Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency, OMIM:202010 Early onset hypertension with raised urinary 18-hydroxy-steroids, steroid-sensitive Tags chimeric-gene
Green Green List (high evidence)	CYP11B2	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Aldosteronism, glucocorticoid-remediable, OMIM:103900 {Low renin hypertension, susceptibility to} Aldosterone to renin ratio raised Tags chimeric-gene
Green Green List (high evidence)	CYP17A1	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes 17,20-lyase deficiency, isolated 202110 17-alpha-hydroxylase/17,20-lyase deficiency 202110 Tags
Green Green List (high evidence)	HSD11B2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Expert Review Green Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes Apparent mineralocorticoid excess, 218030 Tags
Green Green List (high evidence)	KCNJ5	1 review	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Hyperaldosteronism, familial, type III 613677 Tags
Green Green List (high evidence)	KLHL3	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes Pseudohypoaldosteronism, type IID, 614495 Tags
Green Green List (high evidence)	MTX2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Literature Phenotypes Mandibuloacral dysplasia lipodystrophy arterial calcification severe hypertension Tags
Green Green List (high evidence)	NR3C1	1 review	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Expert Review Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Glucocorticoid resistance 615962 Tags
Green Green List (high evidence)	NR3C2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Literature Phenotypes Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy, 605115 Tags
Green Green List (high evidence)	SCNN1B	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Bronchiectasis with or without elevated sweat chloride 1 211400 Liddle syndrome, 177200 Pseudohypoaldosteronism, type I, 264350 Tags
Green Green List (high evidence)	SCNN1G	3 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Bronchiectasis with or without elevated sweat chloride 3, 613071 Liddle syndrome, 177200 Pseudohypoaldosteronism, type I, 264350 Tags
Green Green List (high evidence)	TTC21B	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Phenotypes Hypertension focal segmental glomerulosclerosis nephronopthisis myopia Nephronophthisis 12, OMIM:613820 Tags
Green Green List (high evidence)	WNK1	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Neuropathy, hereditary sensory and autonomic, type II, OMIM:201300 Pseudohypoaldosteronism, type IIC, OMIM:614492 Tags
Green Green List (high evidence)	WNK4	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Pseudohypoaldosteronism, type IIB, 614491 Tags
Amber Amber List (moderate evidence)	CACNA1H	1 review 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber Literature Phenotypes Hyperaldosteronism, familial, type IV 617027 {Epilepsy, childhood absence, susceptibility to, 6} 611942 {Epilepsy, idiopathic generalized, susceptibility to, 6} 611942 Tags
Red Red List (low evidence)	AGT	1 review	Unknown	Sources Expert Review Red Radboud University Medical Center, Nijmegen UKGTN Phenotypes {Hypertension, essential, susceptibility to}, 145500 {Preeclampsia, susceptibility to}Renal tubular dysgenesis, 267430 Tags
Red Red List (low evidence)	AGTR1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Hypertension, essential, 145500 Renal tubular dysgenesis, 267430 Tags
Red Red List (low evidence)	BMPR2	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Radboud University Medical Center, Nijmegen Phenotypes Pulmonary hypertension, familial primary, 1, with or without HHT, 178600, Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associated, 178600, Pulmonary venoocclusive disease 1, 265450 Tags
Red Red List (low evidence)	CAV1	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Lipodystrophy, congenital generalized, type 3, 612526 Pulmonary hypertension, primary, 3, 615343 Tags
Red Red List (low evidence)	CPS1	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Carbamoylphosphate synthetase I deficiency, 237300 {Pulmonary hypertension, neonatal, susceptibility to}, 615371 {Venoocclusive disease after bone marrow transplantation} Tags
Red Red List (low evidence)	CYP21A2	1 review 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Expert Review Red Phenotypes Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency 201910 Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency 201910 Tags
Red Red List (low evidence)	KCNK3	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Pulmonary hypertension, primary, 4, 615344 Tags
Red Red List (low evidence)	PNMT	1 review	Unknown	Sources Expert Review Red Radboud University Medical Center, Nijmegen Tags
Red Red List (low evidence)	PTGIS	1 review	Other - please specifiy in evaluation comments	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Hypertension, essential, 145500 Tags
Red Red List (low evidence)	SARS2	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, 613845 Tags
Red Red List (low evidence)	SMAD9	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Pulmonary hypertension, primary, 2 615342 Tags

Extreme early-onset hypertension (Version 1.21)

9 reviewers

27 Entities

27 reviewed, 15 green

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