Introduction:

Moyamoyavasculopathy (MV) is a chronic progressive vaso‐occlusivedisease affecting the distal intracranial carotid arteries and their proximal branches.Moyamoya disease (MMD) with a strong ethnicity related pattern suggests a genetic determinism.Moyamoya syndrome(MMS)on other hand is known to have associatedrisk factors.  This study aims to unravel genotypic- phenotypic correlation in MV from the Indian cohort.

Materials and methods:

Children between 0-18 years of proven MV (disease /syndrome)were reviewed for clinical presentations, associated risk factors, neuroimaging and treatment. Whole exome sequencing was done for 30/56 patients who consented for the study.

Results:

Total of 56 MV children between age range of 2 – 14yrs (M:F=2.5:1) were identified. Age at first stroke was 6 months to 11 years. Hemiparesis (n=15), Seizures (n=26), headache (n=9), encephalopathy (n=9), TIAs (n=16) were the most common clinical presentations. 44/56 were MMD and 12/56 were MMS (Down’s -2, sickle-2, Thalassemia-2, Seckel-1, Tubercular meningitis -3, Rhabdomyosarcoma with radiation -1, immunodeficiency -1).Surgery was done in 31/56 patients.2/31 had recurrence of stroke post surgery. Novel probably pathogenic variants were identified in 17/21 MMD and 8/9 MMS children.  The most common genes affected were MYH11, MTOR, RNF213, RANBP2, NOTCH1, PCNT and ACSF3and MTFMTgene. These genes code for proteins responsible for vessel wall integrity or oxidative stress resulting in vessel wall damage.

Conclusion :The study concludes that there is definite genetic basis that make certain children susceptible to vasculopathy and should be evaluated for to prevent morbidity and recurrence.