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Genetics Home Reference: your guide to understanding genetic conditions
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Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy

(often shortened to CARASIL)
Reviewed April 2011

What is CARASIL?

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, commonly known as CARASIL, is an inherited condition that causes stroke and other impairments.

Abnormalities affecting the brain and other parts of the nervous system become apparent in an affected person's twenties or thirties. Often, muscle stiffness (spasticity) in the legs and problems with walking are the first signs of the disorder. About half of affected individuals have a stroke or similar episode before age 40. As the disease progresses, most people with CARASIL also develop mood and personality changes, a decline in thinking ability (dementia), memory loss, and worsening problems with movement.

Other characteristic features of CARASIL include premature hair loss (alopecia) and attacks of low back pain. The hair loss often begins during adolescence and is limited to the scalp. Back pain, which develops in early to mid-adulthood, results from the breakdown (degeneration) of the discs that separate the bones of the spine (vertebrae) from one another.

The signs and symptoms of CARASIL worsen slowly with time. Over the course of several years, affected individuals become less able to control their emotions and communicate with others. They increasingly require help with personal care and other activities of daily living; after a few years, they become unable to care for themselves. Most affected individuals die within a decade after signs and symptoms first appear, although few people with the disease have survived for 20 to 30 years.

How common is CARASIL?

CARASIL appears to be a rare condition. It has been identified in about 50 people, primarily in Japan and China.

What genes are related to CARASIL?

CARASIL is caused by mutations in the HTRA1 gene. This gene provides instructions for making an enzyme that is found in many of the body's organs and tissues. One of the major functions of the HTRA1 enzyme is to regulate signaling by proteins in the transforming growth factor-beta (TGF-β) family. TGF-β signaling is essential for many critical cell functions. It also plays an important role in the formation of new blood vessels (angiogenesis).

In people with CARASIL, mutations in the HTRA1 gene prevent the effective regulation of TGF-β signaling. Researchers suspect that abnormally increased TGF-β signaling alters the structure of small blood vessels, particularly in the brain. These blood vessel abnormalities (described as arteriopathy) greatly increase the risk of stroke and lead to the death of nerve cells (neurons) in many areas of the brain. Dysregulation of TGF-β signaling may also underlie the hair loss and back pain seen in people with CARASIL, although the relationship between abnormal TGF-β signaling and these features is less clear.

Related Gene(s)

Changes in this gene are associated with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy.

  • HTRA1

How do people inherit CARASIL?

As its name suggests, this condition is inherited in an autosomal recessive pattern. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of CARASIL?

These resources address the diagnosis or management of CARASIL and may include treatment providers.

  • Gene Review: CARASIL (http://www.ncbi.nlm.nih.gov/books/NBK32533/)
  • Genetic Testing Registry: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1838577)

You might also find information on the diagnosis or management of CARASIL in Educational resources (http://www.ghr.nlm.nih.gov/condition/cerebral-autosomal-recessive-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/cerebral-autosomal-recessive-arteriopathy-with-subcortical-infarcts-and-leukoencephalopathy/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about CARASIL?

You may find the following resources about CARASIL helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for CARASIL?

  • familial young-adult-onset arteriosclerotic leukoencephalopathy with alopecia and lumbago without arterial hypertension
  • Maeda syndrome
  • Nemoto disease

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about CARASIL?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding CARASIL?

alopecia ; angiogenesis ; arteriopathy ; autosomal ; autosomal recessive ; breakdown ; cell ; dementia ; enzyme ; familial ; gene ; growth factor ; hypertension ; inheritance ; inherited ; leukoencephalopathy ; nervous system ; recessive ; spasticity ; subcortical ; syndrome ; white matter

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Fukutake T. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): from discovery to gene identification. J Stroke Cerebrovasc Dis. 2011 Mar-Apr;20(2):85-93. doi: 10.1016/j.jstrokecerebrovasdis.2010.11.008. Epub 2011 Jan 7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21215656?dopt=Abstract)
  • Gene Review: CARASIL (http://www.ncbi.nlm.nih.gov/books/NBK32533/)
  • Hara K, Shiga A, Fukutake T, Nozaki H, Miyashita A, Yokoseki A, Kawata H, Koyama A, Arima K, Takahashi T, Ikeda M, Shiota H, Tamura M, Shimoe Y, Hirayama M, Arisato T, Yanagawa S, Tanaka A, Nakano I, Ikeda S, Yoshida Y, Yamamoto T, Ikeuchi T, Kuwano R, Nishizawa M, Tsuji S, Onodera O. Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. N Engl J Med. 2009 Apr 23;360(17):1729-39. doi: 10.1056/NEJMoa0801560. (http://www.ncbi.nlm.nih.gov/pubmed/19387015?dopt=Abstract)
  • Oide T, Nakayama H, Yanagawa S, Ito N, Ikeda S, Arima K. Extensive loss of arterial medial smooth muscle cells and mural extracellular matrix in cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Neuropathology. 2008 Apr;28(2):132-42. Epub 2007 Nov 6. (http://www.ncbi.nlm.nih.gov/pubmed/18021191?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2011
Published: July 21, 2014