Resolving the biological paradox of aneurysm formation in children with tuberous sclerosis complex

• Published in: JVS-vascular science 2021, Vol.2, p.72-78
• Main Authors: Hedin, Ulf, Brunnström, Hans, Dahlin, Maria, Backman, Torbjörn, Perez de Sa, Valeria, Tran, Phan-Kiet
• Format: Article
• Language: English
• Subjects: Aortic aneurysms; Clinical Medicine; Evidence Summary; Kirurgi; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; mTOR signaling; Smooth muscle cell phenotype; Surgery; Tuberous sclerosis
• ISSN: 2666-3503; 2666-3503
• DOI: 10.1016/j.jvssci.2021.05.003

Aortic aneurysms are rare manifestations in children with tuberous sclerosis complex (TSC) with life threating implications. Although an association between TSC, aortic and other aneurysms has been recognized, mechanistic insights explaining the pathophysiology behind aneurysm development and genetic aberrations in TSC have so far been lacking. Here, we summarize existing knowledge on aneurysms in TSC and present a case of a 2-year-old boy with an infrarenal aortic aneurysm, successfully treated with open aortic reconstruction. Histologic examination of the excised aneurysm wall showed distortion of vessel wall structure with loss of elastin and a pathologic accumulation of smooth muscle cells. Until now, these pathologic features have puzzled researchers as proliferating smooth muscle cells would rather be expected to preserve vessel wall integrity. Recent reports exploring the biological consequences of the dysregulated intracellular signaling pathways in patients with TSC provide plausible explanations to this paradox, which may support the development of future therapeutic strategies.