Neurovascular abnormalities in patients with Loeys-Dietz syndrome type III

• Published in: European journal of medical genetics 2022-02, Vol.65 (2), p.104424-104424, Article 104424
• Main Authors: Dekker, Silvy, Thijssen, Carlijn G.E., Linde, Denise vd, vd Laar, Ingrid M.B.H., Saris, Jasper J., van Es, Adriaan C.G.M., Doormaal, Pieter-Jan van, van Bronswijk, Paul, van Kooten, Fop, Roos-Hesselink, Jolien W.
• Format: Article
• Language: English
• Subjects: Aorta aneurysms osteoarthritis syndrome; Aortic Aneurysm - epidemiology; Arteries - abnormalities; Child; Child, Preschool; Cranial aneurysm/dissection/tortuosity; Female; Humans; Infant; Intracranial Aneurysm - epidemiology; Joint Instability - epidemiology; Loeys-Dietz Syndrome - complications; Loeys-Dietz Syndrome - genetics; Loeys-Dietz Syndrome - pathology; Loeys-Dietz syndrome type III; Male; Neurovascular abnormalities; Phenotype; Skin Diseases, Genetic - epidemiology; SMAD3 mutation; Smad3 Protein - genetics; Vascular Malformations - epidemiology
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2022.104424

The aim of this article is to describe neurovascular findings in patients with Loeys Dietz syndrome type III and their possible clinical impact. Loeys Dietz syndrome type III, caused by pathogenic SMAD3 variants, is an autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis. Neurovascular abnormalities have been described in other heritable aortic syndromes, however, reliable data in Loeys Dietz syndrome type III is missing. In our tertiary center, all adult patients with confirmed Loeys Dietz syndrome type III are followed in a standardized aorta outpatient clinic including Computed Tomography Angiography (CTA) of the head and neck region at baseline and (tri) yearly during follow-up. We performed an analysis of the neurovascular imaging findings and clinical follow-up. The primary outcome was a combined endpoint of mortality, dissection, cerebral vascular event and intervention. In addition, tortuosity and vascular growth were assessed. In total 26 patients (mean age 38.4 years, 38.5% males) underwent 102 (mean 3.9 (1-8) per patient) neurovascular Computed Tomography Angiography scans between 2010 and 2021. In 84.6% some form of neurovascular abnormality was found. The abnormalities at baseline were aneurysm (26.9%) dissection flap (7.7%), arterial tortuosity (61.5%), arterial coiling (23.1%) and arterial kinking (3.8%). During follow up (mean 8.85 (1-11) years) one patient suffered from sudden death and one patient needed a neuro-radiological intervention. No cerebral bleeding or stroke occurred. In conclusion, neurovascular imaging in Loeys Dietz syndrome type III patients revealed abnormalities such as aneurysm, tortuosity, coiling and kinking in the vast majority of patients, but clinical events were rare. Neurovascular screening and follow up is advised in all Loeys Dietz syndrome type III patients.