Early onset dementia (encompassing fronto-temporal dementia and prion disease) (Version 1.83)

Description

Early onset dementia inclusion criteria (29533)
- Progressive cognitive deterioration with change in memory, vision, behaviour or language with functional impairment
- Age at onset <50 years OR
- Later onset with family history of dementia of the same type in a first or second degree relative

Individuals with severe or syndromic disease should be recruited according to standard guidance, typically as trios. Disease status of apparently unaffected participants should be determined according to standard clinical practice to detect cryptic disease. In other cases, unaffected individuals should not be recruited. Recruitment in such families should favour multiplex families over single isolated cases. These singleton recruits will not contribute to the overall singleton monitoring metrics applied to GMCs.

Early onset dementia exclusion criteria (29533)
- Identified underlying cause, e.g. structural brain lesion. NB in uncertain cases with anxiety/depression brain atrophy on imaging, CSF findings or EEG abnormalities should be available to support the diagnosis of a primary degenerative syndrome

Prior genetic testing guidance (29533)
- 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.

Early onset Dementia prior genetic testing genes (29533)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:
- Clinical syndrome Alzheimer disease: PSEN1, APP
- Clinical syndrome FTLD: MAPT, C9ORF72, GRN

Panel Activity

12 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
simon mead (UCL)

Group: GeCIP domain
Workplace: Research lab
Caroline Wright (Genomics England Curator)

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

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

Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)

Group: Other
Workplace: Other
Arianna Tucci (Genomics England Curator)

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

Group: Other
Workplace: Other
Zornitza Stark (Australian Genomics)

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

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

Group: Other
Workplace: Other
Katherine Schon (University of Cambridge)

Group: GeCIP domain
Workplace: NHS clinical service

42 Entities

42 reviewed, 29 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 42 Entitiess
Green Green List (high evidence)	APP	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Green UKGTN Phenotypes Dementia Clinical syndrome Alzheimer disease Tags
Green Green List (high evidence)	ATN1_CAG STR	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green NHS GMS Phenotypes Dentatorubral-pallidoluysian atrophy, OMIM:125370 Tags STR
Green Green List (high evidence)	ATXN10_ATTCT STR	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Spinocerebellar ataxia 10, OMIM:603516 Tags STR
Green Green List (high evidence)	ATXN1_CAG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Spinocerebellar ataxia 1, OMIM:164400 Tags STR
Green Green List (high evidence)	ATXN2_CAG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Spinocerebellar ataxia 2, OMIM:183090 {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090 {Parkinson disease, late-onset, susceptibility to}, OMIM:168600 Tags STR
Green Green List (high evidence)	C9orf72_GGGGCC STR	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green NHS GMS Phenotypes Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550 Tags STR
Green Green List (high evidence)	CHMP2B	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Frontotemporal Dementia Dementia, familial, nonspecific, 600795Amyotrophic lateral sclerosis 17, 614696 Tags
Green Green List (high evidence)	CSF1R	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green UKGTN Phenotypes Leukoencephalopathy, diffuse hereditary, with spheroids, OMIM:221820 Dementia Tags adult-onset
Green Green List (high evidence)	DNAJC5	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes Ceroid lipofuscinosis, neuronal, 4, Parry type 162350 Tags
Green Green List (high evidence)	DNMT1	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Phenotypes Dementia, Deafness, and Sensory Neuropathy Tags
Green Green List (high evidence)	EPM2A	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Radboud University Medical Center, Nijmegen UKGTN Phenotypes Epilepsy, progressive myoclonic 2A (Lafora) 254780 Tags
Green Green List (high evidence)	GRN	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Eligibility statement prior genetic testing Expert Review Green Illumina TruGenome Clinical Sequencing Services UKGTN Phenotypes Frontotemporal Dementia Clinical syndrome FTLD (Frontotemporal lobar degeneration) Tags
Green Green List (high evidence)	HTT_CAG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Huntington disease, OMIM:143100 Tags STR
Green Green List (high evidence)	ITM2B	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Dementia, familial British, OMIM:176500 ABri amyloidosis, MONDO:0008306 Dementia, familial Danish, OMIM:117300 ADan amyloidosis, MONDO:0007297 Tags
Green Green List (high evidence)	JPH3_CTG STR	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green NHS GMS Phenotypes Huntington disease-like 2, OMIM:606438 Tags STR
Green Green List (high evidence)	MAPT	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Dementia, frontotemporal, with or without parkinsonism, 600274 Clinical syndrome FTLD (Frontotemporal lobar degeneration) Tags treatable
Green Green List (high evidence)	NHLRC1	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Epilepsy, progressive myoclonic 2B (Lafora) 254780 Tags
Green Green List (high evidence)	NOP56_GGCCTG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Spinocerebellar ataxia 36, OMIM:614153 Tags STR
Green Green List (high evidence)	NOTCH3	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green UKGTN Phenotypes Dementia Tags
Green Green List (high evidence)	PRNP	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Green UKGTN Phenotypes Dementia Clinical syndrome Prion disease Tags
Green Green List (high evidence)	PSEN1	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Acne inversa, familial, 3, 613737 Alzheimer disease, type 3, 607822 Alzheimer disease, type 3, with spastic paraparesis and apraxia, 607822 Alzheimer disease, type 3, with spastic paraparesis and unusual plaques, 607822 Cardiomyopathy, dilated, 1U, 613694 Dementia, frontotemporal, 600274 Pick disease, 172700 Clinical syndrome Alzheimer disease Tags
Green Green List (high evidence)	PSEN2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green UKGTN Phenotypes Dementia Tags
Green Green List (high evidence)	TARDBP	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services UKGTN Phenotypes Frontotemporal Dementia Tags
Green Green List (high evidence)	TBK1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes FTLD ALS Tags
Green Green List (high evidence)	TBP_CAG STR	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Spinocerebellar ataxia 17, OMIM:607136 {Parkinson disease, susceptibility to}, OMIM:168600 Tags STR
Green Green List (high evidence)	TYROBP	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green UKGTN Phenotypes Dementia Tags
Green Green List (high evidence)	UBQLN2	2 reviews 1 green	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia, 300857 Tags
Green Green List (high evidence)	VCP	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia, 613954 Tags
Green Green List (high evidence)	XK	2 reviews 2 green	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert Review Green Literature Phenotypes McLeod syndrome with or without chronic granulomatous disease, OMIM:300842 McLeod neuroacanthocytosis syndrome, MONDO:0018945 Tags
Red Red List (low evidence)	ATN1	2 reviews 1 red	Other	Sources Expert Review Red Other Phenotypes Dentatorubral-pallidoluysian atrophy, OMIM:125370 Tags currently-ngs-unreportable nucleotide-repeat-expansion
Red Red List (low evidence)	C9orf72	3 reviews 1 green	Other	Sources Eligibility statement prior genetic testing Expert Review Red Illumina TruGenome Clinical Sequencing Services Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN UKGTN Phenotypes Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550 Tags currently-ngs-unreportable nucleotide-repeat-expansion
Red Red List (low evidence)	CHCHD10	1 review 1 red	Not set	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes ?Myopathy, isolated mitochondrial, autosomal dominant, 616209 Tags
Red Red List (low evidence)	DCTN1	1 review	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Other Phenotypes Perry syndrome Tags
Red Red List (low evidence)	FUS	2 reviews 1 green	Not set	Sources Expert Review Red UKGTN Phenotypes Dementia Tags
Red Red List (low evidence)	GBA	1 review	Not set	Sources Radboud University Medical Center, Nijmegen Phenotypes Gaucher disease, type I, 230800 Tags
Red Red List (low evidence)	HNRNPA1	1 review	Not set	Sources Radboud University Medical Center, Nijmegen Phenotypes ?Inclusion body myopathy wtih early-onset Paget disease without frontotemporal Tags
Red Red List (low evidence)	HTRA1	1 review 1 red	Not set	Sources UKGTN Phenotypes Dementia Tags
Red Red List (low evidence)	JPH3	2 reviews 1 red	Other	Sources Expert Review Phenotypes Huntington disease-like 2, OMIM:606438 Tags currently-ngs-unreportable nucleotide-repeat-expansion
Red Red List (low evidence)	SNCA	2 reviews 1 green	Not set	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Parkinson disease 4, 605543 Tags
Red Red List (low evidence)	SNCB	2 reviews 1 red	Not set	Sources Radboud University Medical Center, Nijmegen Phenotypes Dementia, Lewy body, 127750 Tags
Red Red List (low evidence)	TREM2	1 review 1 red	Not set	Sources UKGTN Phenotypes Dementia Tags
No list No list	PPIA	1 review 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Literature Phenotypes amyotrophic lateral sclerosis, MONDO:0004976 Tags

Early onset dementia (encompassing fronto-temporal dementia and prion disease) (Version 1.83)

12 reviewers

42 Entities

42 reviewed, 29 green

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