Key result
Novel TGFB2 deletion variant linked to Loeys-Dietz 4 syndrome in a family with aneurysms.
Case Report
No
A novel TGFB2 mutation (c.280_298del) was identified as the cause of Loeys-Dietz 4 syndrome in a family, highlighting the importance of genetic testing for heritable connective tissue disorders with variable expressivity.
Should not yet change practice; hypothesis-generating for TGFB2 variant expansion in Loeys-Dietz 4.
Background: Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized by vascular and skeletal abnormalities. LDS, classified into six subtypes (LDS1– 6), is caused by mutations in the genes encoding proteins involved in the transforming growth factor-beta (TGF-β) signaling pathway. LDS4 is the mild form of the LDS spectrum, considering that aneurysms are observed in the fourth decade and the disease progression is slower than the other forms. Case Presentation: We reported the case of a novel TGFB2 variant c.280_298del p.(Ser94Profs*7), NM_001135599.2 responsible of LDS4 in a family with sudden death and vascular lesions. Conclusion: The pedigree analysis highlighted the high clinical variability of LDS signs even within the same family. In addition, TGFB2 mutations which do not always lead to vascular phenotype and skeletal signs can be prevalent. We emphasize the relevance of genetic counseling and molecular analysis to identify genetic diseases subtending sudden deaths and to distinguishing heritable connective tissue disorders with phenotypic overlap. Genetic testing can be used to guide clinical management and provide valuable prognostic information.
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Zazzo et al. (2025) conducted a case report in Loeys-Dietz 4 Syndrome. Genetic testing (Next Generation Sequencing) was evaluated on Identification of pathogenic genetic variant. A novel heterozygous deletion variant c.280_298del in the TGFB2 gene was identified as the cause of Loeys-Dietz 4 syndrome in a family presenting with pes planus and a history of aneurysms.
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