Clinical features of familial juvenile cases of moyamoya disease: analysis of patients treated in a single institute over a 28-year period

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The authors compared the clinical features between familial and sporadic cases of moyamoya disease (MMD) by retrospectively analyzing data on patients with MMD registered in the database of Tokyo Medical and Dental University over a period of 28 years.


In total, 383 patients with hospital records at Tokyo Medical and Dental University from 1980 to 2007 were registered into the database. The data on all of these patients were retrospectively reviewed to clarify the occurrence of familial cases. Clinical features of child or adolescent patients (< 20 years of age) with MMD were compared between familial and sporadic cases in a subgroup of patients who were registered after 1995, initially diagnosed using MR angiography, and assessed using an intelligence scale.


Familial occurrence was observed in 59 patients (15.4%) in 40 pedigrees. The clinical features of juvenile patients were analyzed in 124 patients, 22 (17.7%) of whom had familial histories. In comparison with the sporadic cases, patients with familial histories were significantly younger at onset (4.7 vs 6.6 years old), had significantly more cortical infarction (59.1% vs 25.5%), and had significantly more stenoocclusive lesions in the posterior cerebral artery (45.4% vs 24.5%). The rate of patients with intellectual disturbance (intelligence quotient < 75) was significantly larger in the familial cases (47.4%) than in the sporadic cases (17.8%).


This survey of the clinical features of familial MMD suggests that patients with familial MMD had a more serious clinical course in childhood than the sporadic MMD cases.

Abbreviations used in this paper:IQ = intelligence quotient; MMD = moyamoya disease; PCA = posterior cerebral artery.

Article Information

Address correspondence to: Tadashi Nariai, M.D., Ph.D., Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. email:

Please include this information when citing this paper: published online May 31, 2013; DOI: 10.3171/2013.4.PEDS12420.

© AANS, except where prohibited by US copyright law.



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    Patterns of inheritance in familial MMD. There were 40 pedigrees (59 patients) in total.

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    Magnetic resonance angiograms of 2 pairs of identical twins. Two of the patients (A and B) were sisters with MMD, both of whom underwent surgical treatment over a 5-year interval; the other 2 patients (C and D) were also twin sisters. Their identity was confirmed from the birth record of a single placenta. One of the patients (C) presented with severe cerebral infarction at the age of 2 years and was diagnosed with MMD. Meanwhile, her twin sister appeared normal on MR angiography. Thus, the A-B pair were both patients with MMD, while the C-D pair were 1 patient with MMD (C) and 1 normal individual (D).

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    Case 1. Representative neuroradiological findings þf 2 female siblings. A: Axial T2-weighted MR images of an 8-year-old girl (elder sister) when she presented with a large cerebral infarction in the temporooccipital lobe together with a right cerebellar infarction. B: Her initial cerebral angiography images demonstrated bilateral occlusion of internal carotid (IC) arteries and marked development of moyamoya vessels. The angiogram revealed bilateral occlusion of vertebral arteries (VAs) at the extracranial portion (arrows). C: Postoperative external carotid angiogram (ECAG) obtained 1 year after her bilateral indirect bypass surgery demonstrated marked collateral flow to the noninfarcted cerebral cortex. She has remained free from any subsequent infarction or physical deficits, but her final IQ was 52. D: Radiological findings of the younger sister (3 years younger) at diagnosis. Bilateral frontal cortical and subcortical infarction was found at presentation (axial MRI, left). At this stage, she had bilateral IC artery lesions with moyamoya vessels. The IC angiograms and VA angiogram both failed to visualize the left PCA.

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    Case 2. Representative neuroradiological findings of a brother and sister. A: Axial T2-weighted MR images of a 4-year-old boy presenting with a large cortical infarction in the left cerebral hemisphere. B: Two vertebral angiograms obtained in his younger sister: once when she presented with a transient ischemic attack and was diagnosed with MMD at the age of 6 (left), and once when she received final postoperative examination at the age of 11 (right). The peripheral portion of the right PCA was already occluded at the initial diagnosis (left). Five years later, her PCAs were bilaterally occluded. C: Postoperative right and left external carotid angiograms after the sister received bilateral indirect surgery. Marked revascularization was achieved bilaterally. Cerebral infarction did not occur and she has maintained a normal IQ (104) despite severe vascular lesions.



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