Abstract
Background Young adult ischaemic stroke results in considerable mortality and morbidity, yet in most cases, no cause is identified. Loey-Dietz syndrome (LDS) encompasses a constellation of autosomal dominant connective tissue disorders secondary to pathological genetic variants in the Transforming Growth Factor Beta (TGFβ) signalling pathway. It is characterised by arterial tortuosity, aneurysms, and dissections, but can manifest in multi-organ system involvement. LDS3 accounts for approximately 4–6% of LDS cases and is defined by heterozygous pathogenic variants in the Mothers Against Decapentaplegic Homolog 3 (SMAD3) gene, which encodes a transcription factor in the downstream TGFβ signalling cascade. Although abnormalities in supra-aortic vessels, including carotid and vertebral arteries are possible in LDS3, to date there have been no reported cases. We report the first case of spontaneous bilateral vertebral artery dissection related to LDS3 from a novel SMAD3 variant.
Case A 25-year-old male with a new diagnosis of LDS3, presented with unprovoked bilateral vertebral artery dissections and posterior circulation ischaemic stroke. Genetic analysis revealed a novel SMAD3 c.(715 G>C) p.(Glu239Gln) variant. He has no residual clinical signs or symptoms from the ischaemic stroke, but has developed multiple vertebral artery aneurysms. Family screening demonstrated an identical mutation in his mother, who displays a clinical phenotype of severe posterior circulation dolichoectasia without a history of ischaemic stroke.
Conclusions Our case highlights the importance of screening in appropriate patient groups, particularly young adults. Accurately identifying genetic causes of stroke allows for improved patient management including familial screening, access to emerging therapies and pre-implantation genetics.
