Ischemic stroke as an initial manifestation of Loeys-Dietz syndrome type 3 caused by the recurrent p.Arg287Trp variant in SMAD3: a case report with familial context.

BACKGROUND: Loeys-Dietz syndrome type 3 (LDS3) is a rare autosomal dominant connective tissue disorder caused by pathogenic variants in SMAD3. While characteristic features include aortic aneurysm, hypertelorism, and bifid uvula, ischemic stroke as the presenting symptom has been rarely reported.

CASE PRESENTATION: We report a 32-year-old Chinese woman who presented with acute ischemic stroke involving the right occipital lobe and thalamus. Comprehensive vascular imaging revealed multiple arterial abnormalities, including aberrant right subclavian artery with aneurysmal dilatation, right vertebral artery aneurysmal dilatation with multisegmental stenosis, left vertebral artery multifocal segmental severe stenosis, and tortuous intracranial vessels Whole-exome sequencing identified a heterozygous pathogenic variant NM_005902.4:c.859C>T (p.Arg287Trp) in SMAD3. Family history was significant for aortic dissection in her father.

CONCLUSION: This case expands the phenotypic spectrum of LDS3, emphasizing that ischemic stroke may be an underrecognized initial presentation. Early genetic screening in young stroke patients with unusual vascular features may facilitate timely diagnosis and enable appropriate preventive interventions.