A novel NODAL variant in a young embolic stroke patient with visceral heterotaxy

• Published in: BMC neurology 2024-04, Vol.24 (1), p.119-119, Article 119
• Main Authors: Kaburagi, Kei, Hagiwara, Yuta, Tachikawa, Keiji, Miyake, Noriko, Akiyama, Hisanao, Kawai, Yosuke, Omae, Yosuke, Tokunaga, Katsushi, Yamano, Yoshihisa, Shimizu, Takahiro, Mitsuhashi, Satomi
• Format: Article
• Language: English
• Subjects: Activities of daily living; Adolescent; Analysis; Anticoagulants; Cardiac arrhythmia; Cardiovascular Abnormalities; Care and treatment; Case Report; Computed tomography; Congenital diseases; Cryptogenic stroke; CT imaging; Disease; DNA sequencing; Echocardiography; Electrocardiography; Embolic Stroke; Embolisms; Embryogenesis; Families & family life; Genes; Genetic aspects; Genetic counseling; Genetic testing; Genetic variation; Genomes; Health aspects; Heterotaxy Syndrome - genetics; Humans; Ischemia; Magnetic Resonance Imaging; Male; Neuroimaging; Nodal gene; Nucleotide sequencing; Patients; Proteins; Pulmonary arteries; Stroke; Stroke - diagnostic imaging; Stroke - genetics; Stroke patients; Visceral heterotaxy; Whole genome sequencing; Young adults
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/s12883-024-03619-x

Ischemic stroke in young adults can be caused by a variety of etiologies including the monogenic disorders. Visceral heterotaxy is a condition caused by abnormal left-right determinations during embryonic development. We aimed to determine the cause of a young ischemic stroke patient with visceral heterotaxy. We performed neurological, radiological, and genetic evaluations in a 17-year-old male patient presenting ischemic stroke and visceral heterotaxy to determine the underlying cause of this rare disease combination. Brain magnetic resonance imaging (MRI) showed evidence of embolic stroke, abdominal computed tomography (CT) showed visceral heterotaxy, and echocardiogram showed cardiac anomaly with right-to-left-shunt (RLS). Whole genome sequencing (WGS) revealed a heterozygous missense variant (NM_018055.5: c.1016 T > C, p.(Met339Val)) in the NODAL gene, which is essential to the determination of the left-right body axis. Our study highlights the importance of evaluating genetic etiology in young ischemic stroke and the need for stroke risk management in visceral heterotaxy patients with RLS. To the best of our knowledge, we report the first genetically-confirmed case of visceral heterotaxy with young embolic stroke reported to date.