Moyamoya Disease 1

Description

Moyamoya is the name given to a cerebral angiographic picture of bilateral intracranial carotid artery occlusion associated with telangiectatic vessels in the region of the basal ganglia. The Japanese word moyamoya means 'something hazy like a puff of cigarette smoke, drifting in the air.' Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults (summary by Suzuki, 1986).

Genetic Heterogeneity of Moyamoya Disease

The MYMY1 locus maps to chromosome 3p. See also susceptibility to moyamoya disease-2 (MYMY2; 607151), caused by variation in the RNF213 gene (613768) on chromosome 17q25; MYMY3 (608796), which maps to chromosome 8q23; MYMY5 (614042), caused by mutation in the ACTA2 gene (102620) on chromosome 10q23; and MYMY6 with achalasia (615750), caused by mutation in the GUCY1A3 gene (139396) on chromosome 4q32.

See also MYMY4 (300845), an X-linked recessive syndromic disorder characterized by moyamoya disease, short stature, hypergonadotropic hypogonadism, and facial dysmorphism.

Clinical Features

Juvenile patients with moyamoya disease initially present with transient motor disturbances resulting from transient brain ischemia, whereas adults present with intracranial hemorrhage. The symptoms in juvenile patients are due to the narrowing or occlusion of the circle of Willis, and those in adults are due to a collapse of collateral circulation, which gradually develops as a result of the occlusion of the carotid fork at a younger age. Approximately 10% of cases are familial, with approximately 76% occurring in sibs and 24% in a parent and offspring. Because of noninvasive diagnostic methods, the identification of familial cases has increased through the finding of asymptomatic family members (Suzuki, 1986).

Soriani et al. (1993) reported a case of childhood moyamoya disease with clinical onset of neurologic symptoms in the third year of life; during the child's illness, the maternal grandmother presented with moyamoya disease also. Antiplatelet-aggregating and calcium-antagonist drugs seemed effective in preventing further vascular accidents.

Kikuchi et al. (1995) reported moyamoya disease in 3 sibs, a 6-year-old girl and 4-year-old twin boys. No information was provided about the rest of the family.

Dobson et al. (2002) conducted a retrospective study to determine whether the presence of moyamoya collaterals influenced the risk of recurrence of cerebrovascular events in patients with sickle cell disease (603903) placed on chronic transfusions after a stroke. They studied 43 patients with homozygous sickle cell anemia and 1 with HbSO (Arab) (141900.0245) who had suffered strokes before age 18 years. They found that up to 41% of patients with sickle cell disease experienced recurrent cerebrovascular events, stroke or transient ischemic attack, despite chronic transfusions and that the risk of recurrence was significantly higher for those who had moyamoya collaterals. Nagel (2002) commented that the same gene (or a related gene) found in the Japanese familial form of moyamoya disease is involved in a 'multigenic origin of the phenotype' in this complication of a monogenic disorder.

Inheritance

Meschino and Hughes (1989) described moyamoya disease in monozygotic twin boys and in 1 of their brothers. The children were born to consanguineous parents from a socially isolated Mennonite community in Ontario, Canada. Since the Amish and the Mennonites have common genetic backgrounds and similar environmental circumstances, a connection may be worth investigating.

Other Features

Erickson et al. (1980) described 2 sisters with neurofibromatosis (NF1; 162200) and intracranial arterial occlusive disease leading to the moyamoya pattern of collateral circulation. Four other members of their sibship of 8, and members of 2 previous generations, including the mother, had neurofibromatosis.

Echenne et al. (1995) described arteriographically proven moyamoya disease in a 9-year-old girl with hypomelanosis of Ito (300337). They speculated that the association could be that of an unrecognized biologic deficit affecting coagulation. They also reported 2 previous associations of moyamoya disease with von Recklinghausen disease (NF1), tuberous sclerosis (see 191100), encephalotrigeminal angiomatosis, and incontinentia pigmenti (308300).

Yamauchi et al. (2000) stated that more than 50 cases of the association of NF1 and moyamoya disease had been described, including the cases reported Woody et al. (1992) and Barrall and Summers (1996).

Mapping

Ikeda et al. (1999) performed a total genome search to determine the location of a familial moyamoya disease gene, studying 16 families and assuming an unknown mode of inheritance. Linkage was found between the disease and markers located at chromosome 3p26-p24.2. The maximum nonparametric lod score of 3.46 was obtained with marker D3S3050.

Heterogeneity

Aoyagi et al. (1995) found a significant association of human leukocyte antigen B51 in their investigation of 32 unrelated Japanese patients with moyamoya disease. HLA-B51 is believed to be an immunogenetic marker for a subgroup of Behcet disease (109650), associated with Kawasaki disease and idiopathic childhood stroke.

Inoue et al. (2000) analyzed 15 microsatellite markers on chromosome 6 in 20 Japanese sib pairs with moyamoya disease. All patients showed linkage to marker D6S441 on chromosome 6q25. A haplotype region encompassing this marker was shared by 16 families.

Population Genetics

The disorder occurs more frequently in females (male-to-female ratio of 2:3) and is prevalent among patients less than 10 years of age (Suzuki, 1986). Sakurai et al. (2004) stated that the peak age of onset is 10 to 14 years, with a smaller peak of onset age in the 40s.

A high incidence of moyamoya disease is found in Asia, predominantly in Japan (Ikezaki et al., 1997). No single region of Japan has an unusually high incidence (Goto and Yonekawa, 1992).

Yamauchi et al. (2000) stated that Moyamoya disease is the 'most critical cause of childhood stroke in the Japanese population.'

History

Gadoth and Hirsch (1980) observed moyamoya disease in an Amish child who also had pyruvate kinase deficiency (266200). Although PK-deficient red cells show 'spiky' erythrocytes and these may have been a factor in leading to a 'secondary' form of moyamoya, the disorders may have been unrelated.