Moyamoya Syndrome in an Infant with Aicardi–Goutières and Williams Syndromes: A Case Report

Abstract

Stroke in infancy is a rare phenomenon but can lead to significant long-term disability. We present the story of a 6-month-old Old Order Amish infant with underlying Williams syndrome, a rare neurodevelopmental disorder caused by a microdeletion, encompassing the elastin gene that produces abnormalities in elastic fibers of the lungs and vessels. This infant presented with lethargy, irritability, and a new-onset generalized tonic-clonic seizure. Brain magnetic resonance imaging (MRI) was consistent with ischemic stroke in the supratentorial regions. MR angiogram demonstrated bilateral narrowing of the internal carotid arteries with “ivy sign,” suggestive of Moyamoya. Moyamoya disease/syndrome is a cerebrovascular condition that is associated with progressive stenosis of the intracranial vessels and can cause ischemic stroke in young children. Targeted mutation analysis revealed a homozygous c.1411–2A > G splice site variant in the SAMHD1 gene, consistent with a diagnosis of Aicardi–Goutières syndrome type 5 (AGS5), an autosomal recessive condition with multisystem involvement. In our unique case of infantile stroke with Moyamoya syndrome and dual diagnosis of Williams syndrome and AGS5, both diagnoses likely contributed to the cerebrovascular pathology. This case report highlights the importance of suspecting and testing for multiple genetic abnormalities in children presenting with Moyamoya-related stroke.

Early arteriopathy in Aicardi–Goutières syndrome 5. Case report and review of literature

“…We have not been able to find a similar vascular lesion with ischemic sequelae in AGS so early. By reviewing the literature mentioned above, 7–11 only one patient had arteriopathy diagnosed at 6 months of age; 11 in other patients, the vascular disease was established later, between 2 and 37 years, which confirms the claim that pathogenic variants in the SAMHD1 gene have a later manifestation of the disease. 17 The stenotic lesions presented on the first MRI were more affirmative than those demonstrated on subsequent time of flight (TOF) MRA explorations (11 months, 34 months).…”

“…20 The incidence of AGS-5 is rare, and different allelic variants of the SAMHD1 gene have been identified. [7][8][9]11,15,16,21,22 Common clinical manifestations are progressive neurological dysfunction, poor feeding, and irritability. 22 Our case had arterial vasculopathy confirmed by MRI on the eleventh day after birth.…”

“…In the literature review on arteriopathy in AGS, we identified 12 cases described by five authors. 7–11 The blood relation was not encountered in nine individuals, consanguinity was observed in two children, and the third patient with possible consanguinity was born to Old Order Amish parents. Seven patients were female.…”

“…The age of diagnosed arteriopathy ranged from 2 to 37 years; one patient harbored Moyamoya disease at 6 months. 11 The dominant diagnostic method was magnetic resonance angiography (MRA), except in one case where angiography was used. 8 The type of lesion was as follows: aneurysms—two individuals (one experienced fatal intracerebral hemorrhage); unilateral stenosis of the intracranial large–medium vessels with collaterals (quasi-Moyamoya disease)—one case; bilateral stenosis or occlusion of the intracranial large–medium vessels with collateral vessels (Moyamoya disease)–three children; bilateral stenosis/or occlusion of the intracranial large– medium vessels without collateral—four cases.…”

“…Reviewing the available literature, we identified twelve more individuals with arteriopathy in AGS. [7][8][9][10][11]…”