Moyamoya disease

Moyamoya disease may present with stroke in children and young adults. It was first described in 1963; early reports were predominantly in Japanese patients although later reports include non-Japanese:

• RNF213 encodes an unconventional E3 ubiquitin ligase
  • is the major susceptibility gene for moyamoya disease in people from east Asia
  • the Arg4810Lys variant of the gene is most strongly associated with moyamoya disease, but the penetrance is lower than 1%, suggesting a synergistic relationship with additional environmental and genetic risk factors
    • white people carry less common non-Arg4810Lys variants of RNF213
      • partly explains the lower prevalence of moyamoya disease in European countries and in the USA than in east Asian countries
      • several monogenic moyamoya syndromes possess the radiological characteristics of moyamoya disease and have been associated with multiple genes and pathways involved in moyamoya angiopathy pathogenesis (1)
• highest number of cases are seen in East Asia, with more women affected than men (2)
  • based on epidemiological studies, the incidence of MMD is 0.94 and 2.3 per 100,000 individuals in Japan and South Korea, respectively
    • majority of cases are sporadic, around 10%-15% of patients have a family history of MMD

It arises in the presence of bilateral occlusion of the carotid arteries resulting in the development of an extensive fine network of collateral arteries and arterioles at the base of the brain - collaterals resemble a puff of smoke. Children typically present with sudden ischaemic strokes whilst young adults more commonly present with a sub-arachnoid haemorrhage.

• gold standard investigation for diagnosis is cerebral angiography which reveals a smoky appearance of arteries at the base of the skull (2)

There is no specific treatment but surgical revascularisation may be tried.

Reference:

• Ihara M, Yamamoto Y, Hattori Y, Liu W, Kobayashi H, Ishiyama H, Yoshimoto T, Miyawaki S, Clausen T, Bang OY, Steinberg GK, Tournier-Lasserve E, Koizumi A. Moyamoya disease: diagnosis and interventions. Lancet Neurol. 2022 May 20:S1474-4422(22)00165-X
• Gupta A, Tyagi A, Romo M, Amoroso KC, Sonia F. Moyamoya Disease: A Review of Current Literature. Cureus. 2020 Aug 30;12(8):e10141.