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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). [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.

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.

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).

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.
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

Swarup O, Barker JL, Watson R, Davis SM, Campbell BCV, Yassi N
Intern Med J 2023 Jun;53(6):907-916. Epub 2023 Jan 13 doi: 10.1111/imj.15999. PMID: 36565446
van Etten ES, Kaushik K, van Zwet EW, Voigt S, van Walderveen MAA, van Buchem MA, Terwindt GM, Wermer MJH
Stroke 2020 Dec;51(12):3608-3612. Epub 2020 Nov 5 doi: 10.1161/STROKEAHA.120.031264. PMID: 33148142
Montañola A, de Retana SF, López-Rueda A, Merino-Zamorano C, Penalba A, Fernández-Álvarez P, Rodríguez-Luna D, Malagelada A, Pujadas F, Montaner J, Hernández-Guillamon M
Neuromolecular Med 2016 Mar;18(1):99-108. Epub 2015 Dec 14 doi: 10.1007/s12017-015-8381-7. PMID: 26661731

Recent clinical studies

Etiology

Zhang M, Ganz AB, Rohde S, Lorenz L, Rozemuller AJM, van Vliet K, Graat M, Sikkes SAM, Reinders MJT, Scheltens P, Hulsman M, Hoozemans JJM, Holstege H
Alzheimers Dement 2023 Nov;19(11):5036-5047. Epub 2023 Apr 24 doi: 10.1002/alz.13087. PMID: 37092333
Swarup O, Barker JL, Watson R, Davis SM, Campbell BCV, Yassi N
Intern Med J 2023 Jun;53(6):907-916. Epub 2023 Jan 13 doi: 10.1111/imj.15999. PMID: 36565446
Chatterjee P, Fagan AM, Xiong C, McKay M, Bhatnagar A, Wu Y, Singh AK, Taddei K, Martins I, Gardener SL, Molloy MP, Multhaup G, Masters CL, Schofield PR, Benzinger TLS, Morris JC, Bateman RJ, Greenberg SM, Wermer MJH, van Buchem MA, Sohrabi HR, Martins RN; Dominantly Inherited Alzheimer Network
J Alzheimers Dis 2021;79(2):895-903. doi: 10.3233/JAD-201267. PMID: 33361604Free PMC Article
Banerjee G, Carare R, Cordonnier C, Greenberg SM, Schneider JA, Smith EE, Buchem MV, Grond JV, Verbeek MM, Werring DJ
J Neurol Neurosurg Psychiatry 2017 Nov;88(11):982-994. Epub 2017 Aug 26 doi: 10.1136/jnnp-2016-314697. PMID: 28844070Free PMC Article
Kumar-Singh S
Int J Mol Sci 2009 Apr 23;10(4):1872-1895. doi: 10.3390/ijms10041872. PMID: 19468344Free PMC Article

Diagnosis

Zhang M, Ganz AB, Rohde S, Lorenz L, Rozemuller AJM, van Vliet K, Graat M, Sikkes SAM, Reinders MJT, Scheltens P, Hulsman M, Hoozemans JJM, Holstege H
Alzheimers Dement 2023 Nov;19(11):5036-5047. Epub 2023 Apr 24 doi: 10.1002/alz.13087. PMID: 37092333
Swarup O, Barker JL, Watson R, Davis SM, Campbell BCV, Yassi N
Intern Med J 2023 Jun;53(6):907-916. Epub 2023 Jan 13 doi: 10.1111/imj.15999. PMID: 36565446
Sousa L, Coelho T, Taipa R
Neurology 2021 Dec 14;97(24):1111-1119. Epub 2021 Oct 18 doi: 10.1212/WNL.0000000000012965. PMID: 34663645
Chatterjee P, Fagan AM, Xiong C, McKay M, Bhatnagar A, Wu Y, Singh AK, Taddei K, Martins I, Gardener SL, Molloy MP, Multhaup G, Masters CL, Schofield PR, Benzinger TLS, Morris JC, Bateman RJ, Greenberg SM, Wermer MJH, van Buchem MA, Sohrabi HR, Martins RN; Dominantly Inherited Alzheimer Network
J Alzheimers Dis 2021;79(2):895-903. doi: 10.3233/JAD-201267. PMID: 33361604Free PMC Article
Risacher SL, Saykin AJ
Handb Clin Neurol 2019;167:191-227. doi: 10.1016/B978-0-12-804766-8.00012-1. PMID: 31753134Free PMC Article

Therapy

Voigt S, Koemans EA, Rasing I, van Etten ES, Terwindt GM, Baas F, Kaushik K, van Es ACGM, van Buchem MA, van Osch MJP, van Walderveen MAA, Klijn CJM, Verbeek MM, van der Weerd L, Wermer MJH
Trials 2023 Jun 5;24(1):378. doi: 10.1186/s13063-023-07371-4. PMID: 37277877Free PMC Article
Banerjee G, Carare R, Cordonnier C, Greenberg SM, Schneider JA, Smith EE, Buchem MV, Grond JV, Verbeek MM, Werring DJ
J Neurol Neurosurg Psychiatry 2017 Nov;88(11):982-994. Epub 2017 Aug 26 doi: 10.1136/jnnp-2016-314697. PMID: 28844070Free PMC Article
Mehndiratta P, Manjila S, Ostergard T, Eisele S, Cohen ML, Sila C, Selman WR
Neurosurg Focus 2012 Apr;32(4):E7. doi: 10.3171/2012.1.FOCUS11370. PMID: 22463117
Bernstein RA, Gibbs M, Hunt Batjer H
Neurocrit Care 2011 Jun;14(3):453-5. doi: 10.1007/s12028-010-9497-0. PMID: 21246307
Jacobson DR, Buxbaum JN
Adv Hum Genet 1991;20:69-123, 309-11. doi: 10.1007/978-1-4684-5958-6_2. PMID: 1839349

Prognosis

Koemans EA, Castello JP, Rasing I, Abramson JR, Voigt S, Perosa V, van Harten TW, van Zwet EW, Terwindt GM, Gurol ME, Rosand J, Greenberg SM, van Walderveen MAA, Biffi A, Viswanathan A, Wermer MJH
Stroke 2023 Feb;54(2):306-314. Epub 2023 Jan 23 doi: 10.1161/STROKEAHA.122.040823. PMID: 36689586Free PMC Article
Swarup O, Barker JL, Watson R, Davis SM, Campbell BCV, Yassi N
Intern Med J 2023 Jun;53(6):907-916. Epub 2023 Jan 13 doi: 10.1111/imj.15999. PMID: 36565446
Race B, Williams K, Striebel JF, Chesebro B
Neurobiol Dis 2020 Oct;144:105057. Epub 2020 Aug 21 doi: 10.1016/j.nbd.2020.105057. PMID: 32829029
Mehndiratta P, Manjila S, Ostergard T, Eisele S, Cohen ML, Sila C, Selman WR
Neurosurg Focus 2012 Apr;32(4):E7. doi: 10.3171/2012.1.FOCUS11370. PMID: 22463117
Bernstein RA, Gibbs M, Hunt Batjer H
Neurocrit Care 2011 Jun;14(3):453-5. doi: 10.1007/s12028-010-9497-0. PMID: 21246307

Clinical prediction guides

Zhang M, Ganz AB, Rohde S, Lorenz L, Rozemuller AJM, van Vliet K, Graat M, Sikkes SAM, Reinders MJT, Scheltens P, Hulsman M, Hoozemans JJM, Holstege H
Alzheimers Dement 2023 Nov;19(11):5036-5047. Epub 2023 Apr 24 doi: 10.1002/alz.13087. PMID: 37092333
Chatterjee P, Fagan AM, Xiong C, McKay M, Bhatnagar A, Wu Y, Singh AK, Taddei K, Martins I, Gardener SL, Molloy MP, Multhaup G, Masters CL, Schofield PR, Benzinger TLS, Morris JC, Bateman RJ, Greenberg SM, Wermer MJH, van Buchem MA, Sohrabi HR, Martins RN; Dominantly Inherited Alzheimer Network
J Alzheimers Dis 2021;79(2):895-903. doi: 10.3233/JAD-201267. PMID: 33361604Free PMC Article
Cajamarca SA, Norris EH, van der Weerd L, Strickland S, Ahn HJ
Proc Natl Acad Sci U S A 2020 Jun 23;117(25):14482-14492. Epub 2020 Jun 9 doi: 10.1073/pnas.1921327117. PMID: 32518112Free PMC Article
Bulk M, Moursel LG, van der Graaf LM, van Veluw SJ, Greenberg SM, van Duinen SG, van Buchem MA, van Rooden S, van der Weerd L
Stroke 2018 Sep;49(9):2081-2087. doi: 10.1161/STROKEAHA.118.021872. PMID: 30354978
Kumar-Singh S
Int J Mol Sci 2009 Apr 23;10(4):1872-1895. doi: 10.3390/ijms10041872. PMID: 19468344Free PMC Article

Recent systematic reviews

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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