Overview
Cerebral autosomal-recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a genetic disorder which is rare and affects the small blood vessels in the brain and hair follicles.1 Carasil is caused by a mutation in the HTRA1 gene on the arm of chromosome 10.2 The prevalence of Carasil is mostly reported from Japan. Carasil is an autosomal recessive disease. The clinical features of Carasil include recurrent strokes at young age, motor disability, cognitive dysfunction, early onset of hair loss, lower back pain, irritability and behavioural changes. Genetic testing plays a major role in diagnosing Carasil. Managing the symptoms is the primary goal in the treatment of Carasil.
Genetics and molecular pathology
The only gene associated with Carasil is HTRA1. A single nucleotide polymorphism at the promoter region of HTRA1 for which homozygosity for the AA genotype increases the risk of neovascular age-related macular degeneration, has been identified as age-related macular degeneration 7.3 HTRA1 is a serine protease. The pathological changes in people with Carasil include thinning of the outer membrane of the small cerebral arteries, loss of muscle cells, intimal fibrosis and narrowing of the lumen.4
Role of family history in diagnosing Carasil
Carasil follows an autosomal recessive inheritance pattern. Family history plays a major role in the diagnosis of Carasil. Carasil includes an inheritance pattern where two copies (one from each parent) of an abnormal gene is needed to cause the disease. A positive family history with consanguineous marriages can be a suspicious reason for this disease. Similar clinical features among multiple family members point towards Carasil. Identifying the pattern of symptoms in family members helps to diagnose the disease at early stages. Genetic testing identifies HTRA1 mutation. It enables carrier detection and presymptomatic testing in siblings and offsprings. A detailed family history helps in timely intervention. It enables identifying asymptomatic carriers. It also supports genetic counselling.
Challenges in diagnosing Carasil
The main challenge in diagnosing Carasil is due to its resemblance with other small vessel diseases. Incomplete family history brings a challenge in the diagnosis of the disease. Misinterpretation of symptoms puts up a challenge in differentiating Carasil with other conditions.
Management of Carasil
A multidisciplinary approach is needed in the management of Carasil. Education about the disease, psychological and emotional support and supportive care is the mainstay of management for the people affected with Carasil and their families. To compensate for gait disturbance a walking aid can be provided along with medications to relieve spasms. Mood stabilisers can be administered to treat psychological symptoms. Physical therapy and rehabilitation can be provided to enhance mobility. Genetic counselling helps to provide information about the genetic conditions to families. Genetic counsellors can explain the procedure of genetic testing. Research and trials are going on in the treatment aspect of Carasil. Some potential therapies include
- Gene therapy to reinstate HTRA1 function
- Stem cell therapy to enhance vascular repair
FAQs
Is Carasil a rare disease?
Yes, Carasil is a rare genetic disorder.
What are the other names of Carasil?
- Nemoto disease
- Maeda syndrome
- Familial young adult-onset arteriosclerotic leukoencephalopathy with alopecia and lumbago without arterial hypertension
- CADASIL 2
Summary
Carasil is a genetic disorder which is rare and affects small cerebral blood vessels. It follows an autosomal recessive pattern. The symptoms include recurrent strokes, alopecia or hair fall, motor disability, difficulty in walking, gait abnormalities, dementia, cognitive dysfunction and back pain. The sole gene associated with Carasil is HTRA1. Family history helps in diagnosing Carasil to a great extent. An affected individual with Carasil takes over a mutated gene from both the parents. Management of Carasil includes emotional, psychological and supportive care. Genetic counselling and genetic testing helps the family members understand the disease and to manage the symptoms in a positive way.
References
- .Maeda S, Nakayama H, Isaka K, Aihara Y, Nemoto S. Familial unusual encephalopathy of Binswanger's type without hypertension. Folia Psychiatr Neurol Jpn. 1976;30:165–77. doi: 10.1111/j.1440-1819.1976.tb00119.x. [DOI] [PubMed] [Google Scholar]
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- Dewan A, Liu M, Hartman S, et al. HTRA1 promoter polymorphism in wet age-related macular degeneration. Science 2006;314:989-992.
- .Arima K, Yanagawa S, Ito N, Ikeda S. Cerebral arterial pathology of CADASIL and CARASIL (Maeda syndrome). Neuropathology. 2003;23(4):327–334. doi: 10.1046/j.1440-1789.2003.00519.x [DOI] [PubMed] [Google Scholar]Yu Z, Cao S, Wu A, et al. Genetically confirmed CARASIL: case report with novel HTRA1 mutation and literature review. World Neurosurg. 2020;143:121–128. doi: 10.1016/j.wneu.2020.05.128 [DOI] [PubMed] [Google Scholar]
