Clinical polymorphism of heterogeneous types of Loeys–Dietz syndrome in children

Loeys-Dietz syndrome is a monogenic connective tissue disease with an autosomal dominant inheritance pattern. The TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD2, and SMAD3 genes, which are associated with six types of the syndrome, encode components of the transforming growth factor β (TGFβ) signaling pathway. The pathogenesis of the syndrome is associated with impaired signal transmission in this signaling pathway, which leads to impaired structure and function of the connective tissue elements in many organs and systems, including the cardiovascular, respiratory, musculoskeletal, central nervous, and visual systems.

The article presents an analysis of the medical histories of 7 children with types 1 and 2 of Loeys-Dietz syndrome, which was confirmed by molecular genetics (mutations in the TGFBR1 and TGFBR2 genes). All 7 probands had cardiovascular and musculoskeletal disorders, as well as allergic manifestations. It was noted that all patients had abnormalities in their urinary system. The clinical data of a child who inherited the disease from an ill mother are provided in detail.

A differential diagnosis was performed with other phenotypically similar monogenic connective tissue diseases. It is emphasized that medical supervision of patients with Loeys-Dietz syndrome should be carried out with the participation of a clinical geneticist, cardiac and orthopedic surgeons, a nephrologist, an allergist, and an ophthalmologist. The insufficient effectiveness of medical and cardiac surgical methods highlights the importance of developing a pathogenetic therapy for this severe disease.

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