CARASIL

Since CARASIL is autosomal recessive condition, all full brothers and sisters of the affected individual have a 25% chance of having CARASIL too. They also have a 50% chance of being a carrier and a 25% chance of being unaffected and not a carrier. It may be helpful to work with a geneticist or genetic counselor to learn more about who is at risk for CARASIL, hear about the implications of testing, and learn how to get tested. In addition to siblings, the biological parents and children of an individual affected with CARASIL are automatic carriers for one nonworking, mutated copy of the HTRA1 gene. Carriers often do not show signs or symptoms of the condition.

A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Genetic counseling involves discussing potential risks to offspring and reproductive options for young adults who are affected, are carriers, or are at risk of being affected or of being carriers of CARASIL.
Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

A good place to start is speaking with your provider about any patients who are willing or open to meeting other individuals affected by CARASIL. In-person or online support groups through the American Stroke Association may also be good places to find other individuals with CARASIL.

For CARASIL and any inherited disease, the best time to determine genetic risk, clarification of carrier status, or to discuss availability of prenatal testing is before a pregnancy is achieved. Geneticists and genetic counselors are the ideal individuals to assist with education and guidance regarding testing.

To establish the extent of disease and needs in an individual diagnosed with CARASIL, it is typical to have an MRI of the brain and spinal cord. Other tests and evaluations would be based on the signs and symptoms that already may be in place. Your neurologist and geneticist can help develop a plan in order to learn more about your health and monitor disease progression.

Neurologists and medical geneticists are doctors who specialize in the diagnosis and treatment of neurological and genetic conditions and are often familiar with treatment of CARASIL. They may be the coordinating doctor who then refers the patient to other specialists as needed such as pain management, physical therapy, or orthopedics.

Taking medication to lower high blood pressure and not smoking are steps that may help delay the onset of CARASIL health problems or decrease the frequency of stroke episodes.

CARASIL has been reported in individuals from Japan, China, Spain, Turkey, and Italy. However, it can be found in individuals from almost every race and ethnicity.

The care and treatment of an individual with CARASIL is determined by the course of the disease and its signs and symptoms. Follow-up intervals are based on the severity and type of symptoms and the needs of both the affected individuals and their caregivers.

Medications such as Coumadin for anti-platelet therapy and high blood pressure lowering medications may be recommended by your doctor to reduce the occurrence of strokes.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible use in the future. Because it is likely that testing methodology and our understanding of genes, variants, and diseases will improve in the future, affected individuals should consider and be given the option to bank DNA.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, commonly known as CARASIL, is an inherited progressive condition that causes strokes, problems moving, and other nerve and brain functioning issues. Health problems typically begin developing in an affected individual between ages twenty and thirty years. The first signs and symptoms of CARASIL are often muscle stiffness (spasticity) in the legs and problems with walking. These signs and symptoms can worsen slowly with time. As the disease progresses, individuals with CARASIL can also develop mood and personality changes, a decline in thinking ability (dementia), memory loss, and worsening problems with movement. Affected individuals increasingly require help with personal care and other activities of daily living; after a few years they may be completely unable to care for themselves. Most affected individuals die within 10 years after signs and symptoms first appear, however a small number of people with the disease have survived for up to 20 to 30 years.

Research on CADASIL (which is similar to CARASIL) states that smoking may result in earlier disease onset, hypertension (high blood pressure), and may increase the frequency of stroke episodes.

CARASIL is caused by mutations or changes in the HTRA1 [section id="330″ target=”_blank”>gene[/section]. This gene provides instructions for making an enzyme that is found in many of the body’s organs and tissues. The HTRA1 gene helps the regulate "TGF-β signaling". Researchers suspect that abnormally increased TGF-β signaling somehow changes the blood vessels in the brain which increases risks of stroke and other neurological issues.

A variant of unknown significance is an identified gene change that may or may not cause a certain genetic condition or disease. Unfortunately, with a variant of unknown significance there is not enough medical information known to tell if a person with the mutation will development CARASIL related health problems or not. This type of gene change can be called a variant, a variant of uncertain or unknown significance, an unclassified variant, or a VUS.

Genetic conditions can often appear to "run in a family," if more than one person in the family has the condition. Some disorders that affect multiple family members are caused by gene mutations, which can be inherited (passed from parent to child). Other conditions that appear to "run in families" are not caused by mutations environmental factors or a combination of environmental and genetic factors are responsible.

CARASIL is an autosomal recessive disease, which means both copies of the gene have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but often do not show signs or symptoms of the condition. Autosomal recessive disorders are typically not seen in every generation of an affected family.

The letters forming the disease name "CARASIL" stand for the underlying medical problems in CARASIL combined with the pattern in which it runs in families: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy.
C = Cerebral: Found in the large part of the brain, known as the cerebrum. This part of the brain does many things including allowing movement of body parts on purpose, memory, thinking, and decision making.
AR= Autosomal Recessive: CARASIL runs in families in an autosomal recessive pattern. This means that an individual has to inherit two nonworking copies of a specific gene, one from each parent, in order to show symptoms of the disease or condition.
ASIL= Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: A disease of the blood vessels (the arteries) with small areas of dead tissue resulting from lack of oxygen to the cells (infarcts/stroke damage) and nerve fiber disease (white matter changes) in the deep part of the brain under the outer layer of the cerebrum (the cortex).

Often, leg muscle stiffness and problems with walking are the first signs of the disorder. About half of affected individuals have a stroke, mini-stroke (Transient Ischemic Attack), or similar episode before the age of 40. As the disease progresses, most people with CARASIL also develop mood and personality changes, a decline in thinking ability, memory loss, and worsening problems with movement. Other characteristic features of CARASIL include premature hair loss (alopecia) on the scalp and attacks of low back pain. Affected individuals increasingly require help with personal care and other activities of daily living; after a few years they may be completely unable to care for themselves.

Leukodystrophies are a group of rare, progressive, metabolic, genetic diseases that affect the brain, spinal cord and often the peripheral nerves. CARASIL is a type of leukodystrophy.

Individuals with CARASIL should discuss any medications and treatments with their doctor. Because of the increased risk for strokes and/or brain bleeds the following should be avoided.

No special management is necessary in pregnancy for individuals with CARASIL; however, before becoming pregnant, women with CARASIL may need to see a genetic counselor to review medications that may increase the risk for birth defects when taken during pregnancy. They may also wish to talk to a maternal fetal medicine or "high risk" pregnancy doctor to talk about stroke risk and the use of medication during pregnancy.

Genetic testing involves analyzing the HTRA1 gene sequence for changes. You can picture the HTRA1 gene as a long sentence that provides instruction to the body. Sequencing looks for spelling errors in this sentence. Spelling errors can cause the sentence to no longer make sense; and therefore, no longer provide the proper instruction for the body, causing CARASIL. Some labs in the United States just offer sequencing of the HTRA1 gene. Some labs offer panels of many genes involved in early strokes such as a "Teenager Stroke / Stroke-Like Episodes" panel which include testing for the HTRA1 gene.

A genetic professional can help you determine what testing for CARASIL is right for you. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Clinical research can be found at the following:

There is currently no cure for CARASIL. Typically, treatment is geared toward specific symptoms that are apparent in each affected individual. Most frequently, a combination of supportive care and medications to reduce the occurrence of stroke are recommended. Supportive care including emotional support, practical assistance and genetic counseling may be helpful for affected individuals and their families.

There is currently no cure for CARASIL. Typically, treatment is geared toward specific symptoms that are apparent in each affected individual. Most frequently, a combination of supportive care and medications to reduce the occurrence of stroke are recommended. Supportive care including emotional support, practical assistance and genetic counseling may be helpful for affected individuals and their families.
Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

If the HTRA1 gene changes (disease causing mutations) have been identified in an affected family member, prenatal testing for pregnancies at increased risk may be available. Geneticists and genetic counselors can assist with testing coordination. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Carrier testing for family members at risk is possible if the CARASIL pathogenic variants or disease causing mutations in the family have been identified.

A neurologist experienced with genetic causes of stroke or a medical geneticist will know what is expected to occur with CARASIL and will help develop a care and treatment plan. Other specialists may need to be educated as this is a very rare disease. However, these specialists can also provide adequate care through supportive treatment to minimize the impact of the particular symptoms such as back pain or stroke risk.

CARASIL is inherited in an autosomal recessive manner and occurs when an individual inherits two copies of an abnormal or non-functioning gene, one from each parent. If an individual inherits one normal or functioning gene and one abnormal gene for the disease, the person will be a carrier for the disease but typically will not show signs or symptoms.

If you are affected or a carrier of CARASIL your partner would either need to also be affected or be a carrier in order for you to be at risk to have affected children. If you and your partner are both carriers of CARASIL, the risk to have an affected child is 25%. If you are affected and your partner is a CARASIL carrier, the risk to have an affected child is 50%. If both you and your partner are affected, all of your children will be affected. If you are affected, and your partner is not a CARASIL carrier all of your children will be unaffected carriers.

CARASIL is a genetic condition inherited in an autosomal recessive pattern. Autosomal recessive inheritance means that an individual has to inherit two nonworking or mutated copies of a specific gene, one from each parent, in order to show symptoms of the disease or condition. If a couple already has one child with CARASIL, there is a 1 in 4 or 25% risk to have another child with CARASIL.

First, ask your doctors if they know of any existing support groups. If not, ask other types of support groups how they got started. Then, seek out professional assistance before you start a support group. Social service workers, physicians, or therapists may be helpful in various ways, from providing referrals or meeting space to locating other needed resources. Once you think about all the details of your support group (meeting place and time, size of group, goals of group, etc.), reach out to your professional support to see if they will advertise your group.

The following guideline may also be helpful:
https://globalgenes.org/wp-content/uploads/2014/01/GG_toolkit_1final__print.pdf

There are many worthy groups that work on health problems associated with CARASIL.
You can donate to the The United Leukodystrophy Association which includes CARASIL as a supported condition (http://ulf.org/)

American Stroke Association, which is a part of the American Heart Association at: http://www.heart.org/HEARTORG/Giving/Giving_UCM_001137_SubHomePage.jsp. Donations go towards research, education, advocating for better health, improving patient care and reaching populations at risk.

You can also make a donation to the Family Caregiver Alliance (https://www.caregiver.org/donate) which brings information and services to families who provide long-term care at home.

CARASIL is caused by mutations in the HTRA1 gene. Diagnosis of CARASIL can only be confirmed by molecular genetic testing of HTRA1. Genetic testing is typically ordered by a neurologist familiar with genetic causes of early strokes, a geneticist, or a genetic counselor.
A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Check ClinicalTrials.gov for access to information on clinical trials.

In Europe, the EU Clinical Trial Register performs a similar service.

To learn about clinical trials sponsored by private sources, you can contact www.centerwatch.com

CARASIL appears to be a very rare condition. It has been identified in approximately 50 people around the world, primarily in Japan and China.

The genetic material to be tested for CARASIL is most commonly obtained from a blood sample; however, it can also be obtained from the patient’s saliva and from biopsy of certain organs.

Smoking and a high-salt diet are risk factors for stroke and therefore may also increase the risk of stroke associated with CARASIL.

Carriers of autosomal recessive conditions do not typically show signs or symptoms of the disease. As of 2019 it is not clear whether carriers may develop symptoms. Some reports suggest mild symptoms in carriers, however, these symptoms may also be occurring due to typical changes in the brain that arise as we get older. Further studies will be necessary to clarify this issue.

CARASIL is caused by mutations in the HTRA1 gene. Because it is a rare disorder, there may be other genes that could cause CARASIL. However, as of 2019, no other genes are know to cause CARASIL.

Preimplantation genetic diagnosis (PGD), or testing embryos for genetic diseases before returning them into the mother’s uterus, may be an option for some families in which the HTRA1 disease-causing variants have been identified. A genetic counselor can discuss the risks and benefits of PGD with interested individuals before they become pregnant. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Testing of asymptomatic individuals younger than age 18 years who are at risk for adult-onset disorders for which no treatment exists is not considered appropriate. However, testing is always appropriate to consider in symptomatic individuals in a family with an established diagnosis of CARASIL regardless of age.

Magnetic resonance imaging (MRI) is typically used to diagnose CARASIL. A MRI uses a magnetic field and radio waves to produce images of particular organs and tissues, including the brain. Certain factors seen on MRI scans of affected individuals are important, especially white matter changes called leukoencephalopathy and a change called "moyamoya disease" that resembles a puff of smoke in appearance on the scans. Further genetic testing can be used to confirm the presence of the disease.

CARASIL is also known as Maeda syndrome, Nemoto disease, and familial young-adult-onset arteriosclerotic leukoencephalopathy with alopecia and lumbago without arterial hypertension.

Currently, there is not a specific support group for CARASIL; however, The United Leukodystrophy Association (http://ulf.org/) includes CARASIL as a supported condition.
Also, since strokes and/or stroke-like episodes are common issues with CARASIL, the American Stroke Association (http://www.strokeassociation.org/STROKEORG/) may be a helpful online support network for individuals who have had strokes and for their caregivers. The Family Caregiver Alliance (https://www.caregiver.org/) is another group supporting the work of families nationwide caring for loved ones with chronic, disabling health conditions.

An unusual feature of CARASIL includes early baldness and thinning hair that becomes apparent in the teenage years. Another unusual sign seen on a brain MRIs in affected individuals is called "moyamoya disease" and resembles a puff of smoke. Lastly, onset of strokes in patients younger than 40 years old is also a rare finding.

The disease most similar to CARASIL is CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) which is almost identical in symptoms and onset to CARASIL, but is inherited in an autosomal dominant pattern in families. Autosomal dominant inheritance means that an individual only needs to inherit one nonworking copy of a specific gene in order to show symptoms of the disease or condition.

Other diseases that cause early strokes include: HERNS (hereditary endotheliopathy with retinopathy, nephropathy, and stroke), HANAC (hereditary angiopathy with nephropathy, aneurysms and muscle cramps), Fabry disease, Familial cerebral amyloid angiopathy, Familial British dementia, Familial SVD (Portuguese-French type), and Swedish hereditary multi-infarct dementia.