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Hereditary cerebral amyloid angiopathy, Icelandic type

MedGen UID:
279656
•Concept ID:
C1527338
•
Disease or Syndrome
Synonyms: ACys amyloidosis; AMYLOIDOSIS VI; AMYLOIDOSIS, CEREBROARTERIAL, ICELANDIC TYPE; CEREBRAL AMYLOID ANGIOPATHY, CST3-RELATED
SNOMED CT: Hereditary cystatin C amyloid angiopathy (45639009); Icelandic type amyloidosis (45639009); Hereditary cerebral hemorrhage with amyloidosis - Icelandic type (45639009); Hereditary cerebral amyloid angiopathy, Icelandic type (45639009); Amyloidosis VI (45639009); Iceland type amyloidosis (45639009)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): CST3 (20p11.21)
 
Monarch Initiative: MONDO:0007098
OMIM®: 105150
Orphanet: ORPHA100008

Definition

Cerebral amyloid angiopathy (CAA), defined by the deposition of congophilic material in the vessels of the cortex and leptomeninges, is a major cause of intracerebral hemorrhage in the elderly (Vinters, 1987, Greenberg, 1998). Palsdottir et al. (1988) referred to the disorder in Icelandic patients as hereditary cystatin C amyloid angiopathy (HCCAA). For a discussion of genetic heterogeneity of CAA, see 605714. [from OMIM]

Additional description

From MedlinePlus Genetics
Two types of hereditary cerebral amyloid angiopathy, known as familial British dementia and familial Danish dementia, are characterized by dementia and movement problems. Strokes are uncommon in these types. People with the Danish type also have clouding of the lens of the eyes (cataracts) and deafness.

Strokes are rare in people with the Arctic type of hereditary cerebral amyloid angiopathy, in which the first sign is usually memory loss that then progresses to severe dementia. Strokes are also uncommon in individuals with the Iowa type. This type is characterized by memory loss, problems with vocabulary and the production of speech, personality changes, and involuntary muscle twitches (myoclonus).

The first sign of the Icelandic type of hereditary cerebral amyloid angiopathy is typically a stroke followed by dementia. Strokes associated with the Icelandic type usually occur earlier than the other types, with individuals typically experiencing their first stroke in their twenties or thirties.

People with the Flemish and Italian types of hereditary cerebral amyloid angiopathy are prone to recurrent strokes and dementia. Individuals with the Piedmont type may have one or more strokes and typically experience impaired movements, numbness or tingling (paresthesias), confusion, or dementia.

The Dutch type of hereditary cerebral amyloid angiopathy is the most common form. Stroke is frequently the first sign of the Dutch type and is fatal in about one third of people who have this condition. Survivors often develop dementia and have recurrent strokes. About half of individuals with the Dutch type who have one or more strokes will have recurrent seizures (epilepsy).

There are many different types of hereditary cerebral amyloid angiopathy. The different types are distinguished by their genetic cause, which determines whether areas of the brain other than blood vessels are affected, and the signs and symptoms that occur. The various types of hereditary cerebral amyloid angiopathy are named after the regions where they were first diagnosed.

Hereditary cerebral amyloid angiopathy is a condition characterized by an abnormal buildup of protein clumps called amyloid deposits in the blood vessels in the brain, causing vascular disease (angiopathy). People with hereditary cerebral amyloid angiopathy often have progressive loss of intellectual function (dementia), stroke, and other neurological problems starting in mid-adulthood. Due to neurological decline, this condition is typically fatal in one's sixties, although there is variation depending on the severity of the signs and symptoms. Most affected individuals die within a decade after signs and symptoms first appear, although some people with the disease have survived longer.  https://medlineplus.gov/genetics/condition/hereditary-cerebral-amyloid-angiopathy

Clinical features

From HPO
Stroke disorder
MedGen UID:
52522
•Concept ID:
C0038454
•
Disease or Syndrome
Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain.
Intracranial hemorrhage
MedGen UID:
101799
•Concept ID:
C0151699
•
Pathologic Function
Hemorrhage occurring within the skull.
Cerebral hemorrhage
MedGen UID:
423648
•Concept ID:
C2937358
•
Pathologic Function
Hemorrhage into the parenchyma of the brain.
Dementia
MedGen UID:
99229
•Concept ID:
C0497327
•
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Cerebral amyloid angiopathy
MedGen UID:
38998
•Concept ID:
C0085220
•
Disease or Syndrome
Hereditary cerebral amyloid angiopathy is a condition characterized by an abnormal buildup of protein clumps called amyloid deposits in the blood vessels in the brain, causing vascular disease (angiopathy). People with hereditary cerebral amyloid angiopathy often have progressive loss of intellectual function (dementia), stroke, and other neurological problems starting in mid-adulthood. Due to neurological decline, this condition is typically fatal in one's sixties, although there is variation depending on the severity of the signs and symptoms. Most affected individuals die within a decade after signs and symptoms first appear, although some people with the disease have survived longer.\n\nThere are many different types of hereditary cerebral amyloid angiopathy. The different types are distinguished by their genetic cause, which determines whether areas of the brain other than blood vessels are affected, and the signs and symptoms that occur. The various types of hereditary cerebral amyloid angiopathy are named after the regions where they were first diagnosed.\n\nThe Dutch type of hereditary cerebral amyloid angiopathy is the most common form. Stroke is frequently the first sign of the Dutch type and is fatal in about one third of people who have this condition. Survivors often develop dementia and have recurrent strokes. About half of individuals with the Dutch type who have one or more strokes will have recurrent seizures (epilepsy).\n\nPeople with the Flemish and Italian types of hereditary cerebral amyloid angiopathy are prone to recurrent strokes and dementia. Individuals with the Piedmont type may have one or more strokes and typically experience impaired movements, numbness or tingling (paresthesias), confusion, or dementia.\n\nThe first sign of the Icelandic type of hereditary cerebral amyloid angiopathy is typically a stroke followed by dementia. Strokes associated with the Icelandic type usually occur earlier than the other types, with individuals typically experiencing their first stroke in their twenties or thirties.\n\nStrokes are rare in people with the Arctic type of hereditary cerebral amyloid angiopathy, in which the first sign is usually memory loss that then progresses to severe dementia. Strokes are also uncommon in individuals with the Iowa type. This type is characterized by memory loss, problems with vocabulary and the production of speech, personality changes, and involuntary muscle twitches (myoclonus).\n\nTwo types of hereditary cerebral amyloid angiopathy, known as familial British dementia and familial Danish dementia, are characterized by dementia and movement problems. Strokes are uncommon in these types. People with the Danish type also have clouding of the lens of the eyes (cataracts) and deafness.
Generalized amyloid deposition
MedGen UID:
354872
•Concept ID:
C1862968
•
Finding
A diffuse form of amyloidosis.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary cerebral amyloid angiopathy, Icelandic type
Follow this link to review classifications for Hereditary cerebral amyloid angiopathy, Icelandic type in Orphanet.

Professional guidelines

PubMed

Brunet de Courssou JB, Gorza L, Babin M, Nasser G, Ancelet C, Labeyrie C, Denier C, Cauquil C
Rev Neurol (Paris) 2025 Oct;181(8):801-807. Epub 2025 Aug 14 doi: 10.1016/j.neurol.2025.07.012. PMID: 40816926
Sekijima Y, Sousa L
Amyloid 2025 Jun;32(2):117-128. Epub 2024 Dec 3 doi: 10.1080/13506129.2024.2435573. PMID: 39627935
van der Zwet R, Koemans EA, Voigt S, van Dort R, Rasing I, Kaushik K, van Harten TW, Schipper MR, Terwindt GM, van Osch M, van Walderveen M, van Etten ES, Wermer M
Int J Stroke 2024 Oct;19(8):942-946. Epub 2024 Mar 21 doi: 10.1177/17474930241239801. PMID: 38444323Free PMC Article

Recent clinical studies

Etiology

Sousa L, Coelho T, Fernandes J, Cardoso M, Alves C, da Silva AM, Sousa AP, Pinto MM, Pereira RM, Ruano L, Lemos C, Baldeiras I, Reis C, Taipa R
J Neurol 2026 Sep 20;273(10) doi: 10.1007/s00415-026-14146-9. PMID: 42763823Free PMC Article
Khaki PSS, Guillen-Poza PA, Wong C, Kan C, Sharma R, Sugimura R, Robinson AC, Valbuena A, Ng RC, Yang Y, Hervas R
Nat Struct Mol Biol 2026 Aug;33(8):1194-1203. Epub 2026 Aug 6 doi: 10.1038/s41594-026-01855-y. PMID: 42562893
van Dort R, van Stek-Smits VCJ, Schriemer SE, van der Zwet RGJ, Schipper MR, Voigt S, Hart EP, Easwaran V, Sohrabi HR, Taddei K, Gardener SL, Martins RN, Greenberg SM, van Osch MJP, van Walderveen MAA, Wermer MJH, van Etten ES
Alzheimers Dement 2026 Jul;22(7):e71629. doi: 10.1002/alz.71629. PMID: 42360287Free PMC Article
Mercado C, Amaro A, Martinez-Pinto J, Vidal R, Jury-Garfe N, Lasagna-Reeves CA
bioRxiv 2026 Apr 19 doi: 10.64898/2026.04.17.719285. PMID: 42039545Free PMC Article
Bastrup JA, Folke J, Kaalund SS, Rasmussen M, Aznar S, Jepps T
Geroscience 2026 Dec;48(6):8265-8283. Epub 2026 Feb 4 doi: 10.1007/s11357-026-02097-y. PMID: 41634446Free PMC Article

Diagnosis

van der Plas MC, van Dort R, Rasing I, Long Y, van Zwet EW, van Osch MJP, Sohrabi HR, Taddei K, Gardener SL, Martins RN, Greenberg SM, Terwindt GM, van Walderveen MAA, Wermer MJH
J Stroke Cerebrovasc Dis 2026 Apr;35(4):108593. Epub 2026 Feb 16 doi: 10.1016/j.jstrokecerebrovasdis.2026.108593. PMID: 41707816
Hendrickx Van de Craen E, Bossaerts L, Sieben A, Van den Bossche T, Bjerke M, Hanseeuw B, Bergmans B, Vandenberghe R, De Deyn PP, Cras P, Sleegers K, Engelborghs S, Van Broeckhoven C, van der Zee J; BELNEU Consortium
Neurobiol Aging 2026 Apr;160:33-46. Epub 2026 Jan 1 doi: 10.1016/j.neurobiolaging.2025.12.010. PMID: 41494406
Coleman CI, Martinez R, Torres SA
Curr Med Res Opin 2025 Nov;41(11):2013-2024. Epub 2025 Dec 8 doi: 10.1080/03007995.2025.2596820. PMID: 41359351
Brunet de Courssou JB, Gorza L, Babin M, Nasser G, Ancelet C, Labeyrie C, Denier C, Cauquil C
Rev Neurol (Paris) 2025 Oct;181(8):801-807. Epub 2025 Aug 14 doi: 10.1016/j.neurol.2025.07.012. PMID: 40816926
Singh J, Hegazy MI
2025 Jan PMID: 32310565

Therapy

Neubauer A, Feyen P, Pekrun S, Roeber S, Ruf V, Strübing FL, Herms J
Acta Neuropathol 2026 Oct 7;152(1) doi: 10.1007/s00401-026-03096-1. PMID: 42841982Free PMC Article
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Prognosis

Neubauer A, Feyen P, Pekrun S, Roeber S, Ruf V, Strübing FL, Herms J
Acta Neuropathol 2026 Oct 7;152(1) doi: 10.1007/s00401-026-03096-1. PMID: 42841982Free PMC Article
van Dort R, van Stek-Smits VCJ, Schriemer SE, van der Zwet RGJ, Schipper MR, Voigt S, Hart EP, Easwaran V, Sohrabi HR, Taddei K, Gardener SL, Martins RN, Greenberg SM, van Osch MJP, van Walderveen MAA, Wermer MJH, van Etten ES
Alzheimers Dement 2026 Jul;22(7):e71629. doi: 10.1002/alz.71629. PMID: 42360287Free PMC Article
van der Plas MC, van Dort R, Rasing I, Long Y, van Zwet EW, van Osch MJP, Sohrabi HR, Taddei K, Gardener SL, Martins RN, Greenberg SM, Terwindt GM, van Walderveen MAA, Wermer MJH
J Stroke Cerebrovasc Dis 2026 Apr;35(4):108593. Epub 2026 Feb 16 doi: 10.1016/j.jstrokecerebrovasdis.2026.108593. PMID: 41707816
Sykora M, Harmackova M, Parobkova E, Rusina R, Matěj R
Front Neurosci 2025;19:1703718. Epub 2026 Jan 2 doi: 10.3389/fnins.2025.1703718. PMID: 41551043Free PMC Article
Singh J, Hegazy MI
2025 Jan PMID: 32310565

Clinical prediction guides

van der Plas MC, van Dort R, Rasing I, Long Y, van Zwet EW, van Osch MJP, Sohrabi HR, Taddei K, Gardener SL, Martins RN, Greenberg SM, Terwindt GM, van Walderveen MAA, Wermer MJH
J Stroke Cerebrovasc Dis 2026 Apr;35(4):108593. Epub 2026 Feb 16 doi: 10.1016/j.jstrokecerebrovasdis.2026.108593. PMID: 41707816
Bastrup JA, Folke J, Kaalund SS, Rasmussen M, Aznar S, Jepps T
Geroscience 2026 Dec;48(6):8265-8283. Epub 2026 Feb 4 doi: 10.1007/s11357-026-02097-y. PMID: 41634446Free PMC Article
Hendrickx Van de Craen E, Bossaerts L, Sieben A, Van den Bossche T, Bjerke M, Hanseeuw B, Bergmans B, Vandenberghe R, De Deyn PP, Cras P, Sleegers K, Engelborghs S, Van Broeckhoven C, van der Zee J; BELNEU Consortium
Neurobiol Aging 2026 Apr;160:33-46. Epub 2026 Jan 1 doi: 10.1016/j.neurobiolaging.2025.12.010. PMID: 41494406
Choudhury A, Yesiltepe M, Lashley T, Singh V, Minhas V, Yin T, Fernandez A, D'Adamio L, Ahn HJ
J Neuroinflammation 2025 Dec 7;22(1):287. doi: 10.1186/s12974-025-03537-w. PMID: 41354963Free PMC Article
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Neuropathology 2025 Aug;45(4):e70011. Epub 2025 May 26 doi: 10.1111/neup.70011. PMID: 40418931

Recent systematic reviews

Coleman CI, Martinez R, Torres SA
Curr Med Res Opin 2025 Nov;41(11):2013-2024. Epub 2025 Dec 8 doi: 10.1080/03007995.2025.2596820. PMID: 41359351
Voigt S, Voigt S, Rasing I, van der Plas MC, Khidir SJH, Koemans EA, Kaushik K, van Etten ES, Schoones JW, van Zwet EW, Wermer MJH
Cerebrovasc Dis 2025;54(5):746-760. Epub 2024 Nov 18 doi: 10.1159/000542666. PMID: 39557031Free PMC Article
Biffi A
Cereb Circ Cogn Behav 2022;3:100124. Epub 2022 Feb 20 doi: 10.1016/j.cccb.2022.100124. PMID: 36324420Free PMC Article
Biffi E, Turple Z, Chung J, Biffi A
PLoS One 2022;17(4):e0266974. Epub 2022 Apr 14 doi: 10.1371/journal.pone.0266974. PMID: 35421194Free PMC Article
Rannikmäe K, Samarasekera N, Martînez-Gonzâlez NA, Al-Shahi Salman R, Sudlow CL
J Neurol Neurosurg Psychiatry 2013 Aug;84(8):901-8. Epub 2013 Mar 2 doi: 10.1136/jnnp-2012-303898. PMID: 23457231

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