What are the other Names for this Condition? (Also known as/Synonyms)

• Primary Moyamoya Disease
• Secondary Moyamoya Disease
• Spontaneous Occlusion of the Circle of Willis

What is Moyamoya Disease? (Definition/Background Information)

• Moyamoya Disease (MMD) is a rare, progressive, blood vessel disease caused by blocked arteries at the base of the brain in an area called the basal ganglia
• The name "moyamoya" means "puff of smoke" in Japanese and describes the look of the tangled vessels that form to compensate for the blockage. This condition usually affects children, but can affect adults
• Affected people are at increased risk for blood clots, strokes, and transient ischemic attacks (TIAs) which are frequently accompanied by seizures and muscular weakness, or paralysis on one side of the body
• Affected people may also have disturbed consciousness, speech deficits (usually aphasia), sensory and cognitive impairments, involuntary movements, and vision problems
• Researchers believe that Moyamoya Disease is an inherited condition because it tends to run in families
• Moyamoya syndrome is a related term that refers to cases of Moyamoya Disease that occur in association with other conditions or risk factors, such as neurofibromatosis, tuberculosis meningitis, sickle cell disease, leptospirosis, brain tumors, Sturge-Weber syndrome, and tuberous sclerosis

(Source: Moyamoya Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Moyamoya Disease? (Age and Sex Distribution)

• Moyamoya Disease is a rare congenital disorder that can affect individuals of all ages. However, most cases are reported in children
• The condition can occur in both males and females
• Although MMD can affect all populations worldwide, it is more prevalent in individuals of Asian descent. The frequency of occurrence in Japan is estimated to be between 1:9,500 to 1:30,000, compared to 1:1,100,000 in the United States

What are the Risk Factors for Moyamoya Disease? (Predisposing Factors)

The risk factors for Moyamoya Disease may include:

• A family history of the disorder
• Inherited connective tissue disorders
• Chromosomal disorders
• Autoimmune conditions
• Atherosclerosis
• Infections
• Blood and vascular disorders
• Metabolic diseases
• Heart disease
• Brain tumors
• Exposure to radiation
• Head trauma

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Moyamoya Disease? (Etiology)

Moyamoya Disease may by caused by heritable mutation(s) in the RNF213 or ACTA2 gene.

• Additionally, mutation(s) in other unidentified genes may cause the disorder. In some cases, more than one gene may be involved in the development of this disease
• Moyamoya Disease can also occur as Moyamoya Syndrome, in association with other inherited or acquired disorders, such as the following:
  • Inherited connective tissue disorders (such as neurofibromatosis)
  • Chromosomal disorders (such as Down syndrome)
  • Autoimmune conditions (such as lupus)
  • Atherosclerosis
  • Infections
  • Blood disorders (such as sickle cell disease)
  • Vascular disorders (such as vasculitis)
  • Metabolic diseases
  • Heart disease
  • Brain tumors
  • Exposure to radiation
  • Head trauma
• Moyamoya Disease may follow an autosomal dominant, autosomal recessive, or X-linked inheritance pattern

Autosomal dominant pattern of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

X-linked recessive pattern: The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

What are the Signs and Symptoms of Moyamoya Disease?

The signs and symptoms of Moyamoya Disease may include:

• Inflammatory Arteriopathy
• Very frequently present symptoms in 80-99% of the cases: Telangiectasia

Frequently present symptoms in 30-79% of the cases:

• Abnormality of the cerebral vasculature
• Intellectual disability
• Seizures 
• Ventriculomegaly

(Source: Moyamoya Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Moyamoya Disease Diagnosed?

Moyamoya Disease is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies, including cerebral angiography for confirmation
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm known causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Moyamoya Disease?

The complications of Moyamoya Disease may include:

• Risk of falls and injury due to seizures
• Involuntary movements
• Transient ischemic attacks
• Stroke
• Hemiparesis
• Paralysis
• Intracranial hemorrhage

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Moyamoya Disease Treated?

The treatment for Moyamoya Disease may include the following:

• Surgery to correct malformations, if any
• Revascularization surgeries to bypass blocked arteries
• Use of medications such as:
  • Blood thinners (aspirin) to minimize blood clot formation
  • Calcium channel blocker to address symptoms associated with transient ischemic attacks
  • Anti-seizure medications
  • If necessary, anti-coagulant medications

How can Moyamoya Disease be Prevented?

Currently, Moyamoya Disease that is inherited or associated with inherited conditions may not be preventable.

• Genetic testing of the expecting parents (and related family members), if available, and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Taking precautions to avoid head trauma may help prevent Moyamoya Disease associated with such injuries
• Seeking medical attention for pre-existing conditions (such as atherosclerosis and infections) that may lead to Moyamoya Disease may help prevent the occurrence of this disorder
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Moyamoya Disease? (Outcomes/Resolutions)

• The prognosis of Moyamoya Disease is dependent upon the severity of the signs and symptoms and associated complications, if any
• Without treatment, the condition is progressive and may result in recurrent strokes and intracranial hemorrhage, which may be fatal
• A long-term follow-up study of poor outcomes were reported in 50-66% of untreated individuals, due to progressive neurologic deficits
• Approximately 10% of adults and 4.3% of the children affected by Moyamoya Disease succumb to the condition

Additional and Relevant Useful Information for Moyamoya Disease:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/