CARASIL: Difference between revisions

Revision as of 16:45, 5 March 2025

A rare genetic disorder affecting the brain's small blood vessels

CARASIL (Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a rare genetic disorder that affects the small blood vessels in the brain. It is characterized by a combination of neurological and non-neurological symptoms, including subcortical infarcts, leukoencephalopathy, alopecia, and spondylosis.

Genetics

CARASIL is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder. The condition is caused by mutations in the HTRA1 gene, which encodes a serine protease involved in the regulation of TGF-beta signaling.

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Autosomal recessive inheritance pattern

Pathophysiology

The HTRA1 gene mutations lead to a loss of function of the HTRA1 protein, resulting in abnormal TGF-beta signaling. This disruption affects the integrity and function of the small blood vessels in the brain, leading to the characteristic features of CARASIL. The vascular changes result in ischemic events and white matter changes, contributing to the neurological symptoms.

Clinical Features

CARASIL typically presents in early adulthood, although symptoms can appear in adolescence. The main clinical features include:

Neurological symptoms: Progressive dementia, pseudobulbar palsy, and ataxia are common. Patients may also experience stroke-like episodes due to subcortical infarcts.
Alopecia: Early-onset hair loss is a distinctive feature of CARASIL, often occurring in the second or third decade of life.
Spondylosis: Degenerative changes in the spine, particularly in the lumbar region, are frequently observed.

Diagnosis

The diagnosis of CARASIL is based on clinical evaluation, neuroimaging, and genetic testing. MRI scans typically reveal leukoencephalopathy and subcortical infarcts. Genetic testing can confirm the presence of mutations in the HTRA1 gene.

Management

There is currently no cure for CARASIL, and treatment is primarily supportive. Management focuses on alleviating symptoms and preventing complications. Physical therapy, occupational therapy, and speech therapy may be beneficial for managing neurological symptoms. Regular monitoring and management of cardiovascular risk factors are also important.

Prognosis

The prognosis for individuals with CARASIL varies, but the condition is progressive and can lead to significant disability. The rate of progression and severity of symptoms can differ among affected individuals.

Related pages

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-{{Short description|A rare genetic disorder affecting the brain and blood vessels}}
+{{Short description|A rare genetic disorder affecting the brain's small blood vessels}}
 {{Use dmy dates|date=October 2023}}
-'''CARASIL''' (Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a rare [[genetic disorder]] characterized by a combination of neurological and dermatological symptoms. It is an [[autosomal recessive]] condition, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disease.
+'''CARASIL''' (Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a rare [[genetic disorder]] that affects the small blood vessels in the [[brain]]. It is characterized by a combination of neurological and non-neurological symptoms, including [[subcortical infarcts]], [[leukoencephalopathy]], [[alopecia]], and [[spondylosis]].
 ==Genetics==
-[[File:Autosomal_recessive_-_en.svg|thumb|right|Diagram showing autosomal recessive inheritance pattern]]
+CARASIL is inherited in an [[autosomal recessive]] manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disorder. The condition is caused by mutations in the ''[[HTRA1]]'' gene, which encodes a serine protease involved in the regulation of [[TGF-beta signaling]].
-CARASIL is caused by mutations in the ''HTRA1'' gene, which is located on chromosome 10. The ''HTRA1'' gene encodes a serine protease enzyme that is involved in the degradation of proteins in the extracellular matrix. Mutations in this gene lead to the accumulation of abnormal proteins, which affects the integrity of small blood vessels in the brain.
+[[File:Autosomal_recessive_-_en.svg|Autosomal recessive inheritance pattern|thumb|right]]
+==Pathophysiology==
+The ''HTRA1'' gene mutations lead to a loss of function of the HTRA1 protein, resulting in abnormal [[TGF-beta]] signaling. This disruption affects the integrity and function of the small blood vessels in the brain, leading to the characteristic features of CARASIL. The [[vascular changes]] result in [[ischemic events]] and [[white matter]] changes, contributing to the neurological symptoms.
 ==Clinical Features==
-The clinical presentation of CARASIL includes a range of symptoms that typically begin in early adulthood. The most prominent features are:
+CARASIL typically presents in early adulthood, although symptoms can appear in adolescence. The main clinical features include:
-===Neurological Symptoms===
-* '''Subcortical Infarcts''': Patients experience multiple small strokes, leading to progressive [[cognitive decline]] and [[dementia]].
-* '''Leukoencephalopathy''': This refers to changes in the white matter of the brain, visible on [[magnetic resonance imaging]] (MRI) scans, which contribute to neurological deficits.
-* '''Gait Disturbance''': Difficulty in walking due to spasticity and weakness is common.
-===Dermatological Symptoms===
+* '''Neurological symptoms''': Progressive [[dementia]], [[pseudobulbar palsy]], and [[ataxia]] are common. Patients may also experience [[stroke]]-like episodes due to subcortical infarcts.
-* '''Alopecia''': Early-onset hair loss, particularly affecting the scalp, is a characteristic feature.
+* '''Alopecia''': Early-onset [[hair loss]] is a distinctive feature of CARASIL, often occurring in the second or third decade of life.
-* '''Spondylosis''': Degenerative changes in the spine, leading to back pain and stiffness.
+* '''Spondylosis''': Degenerative changes in the [[spine]], particularly in the [[lumbar region]], are frequently observed.
 ==Diagnosis==
-The diagnosis of CARASIL is based on clinical evaluation, family history, and genetic testing. MRI scans are used to identify characteristic changes in the brain, while genetic testing confirms mutations in the ''HTRA1'' gene.
+The diagnosis of CARASIL is based on clinical evaluation, [[neuroimaging]], and genetic testing. [[MRI]] scans typically reveal [[leukoencephalopathy]] and subcortical infarcts. Genetic testing can confirm the presence of mutations in the ''HTRA1'' gene.
 ==Management==
-There is currently no cure for CARASIL, and treatment is primarily supportive. Management focuses on alleviating symptoms and preventing complications. This may include:
+There is currently no cure for CARASIL, and treatment is primarily supportive. Management focuses on alleviating symptoms and preventing complications. [[Physical therapy]], [[occupational therapy]], and [[speech therapy]] may be beneficial for managing neurological symptoms. Regular monitoring and management of [[cardiovascular risk factors]] are also important.
-* '''Physical Therapy''': To improve mobility and manage spasticity.
-* '''Cognitive Therapy''': To support cognitive function and manage dementia.
-* '''Pain Management''': For symptoms related to spondylosis.
 ==Prognosis==
-The progression of CARASIL is variable, but it generally leads to significant disability over time. The disease course is progressive, with worsening neurological and physical symptoms.
+The prognosis for individuals with CARASIL varies, but the condition is progressive and can lead to significant disability. The rate of progression and severity of symptoms can differ among affected individuals.
 ==Related pages==
-* [[Genetic disorder]]
+* [[CADASIL]]
 * [[Leukoencephalopathy]]
-* [[Dementia]]
+* [[Genetic disorders]]
-* [[Stroke]]
 [[Category:Genetic disorders]]
 [[Category:Neurological disorders]]
-[[Category:Dermatologic disorders]]
+[[Category:Rare diseases]]