Loeys-Dietz syndrome is a genetic disorder that is caused by a mutation (gene change) in either the TGFBR1 or TGFBR2 genes (transforming growth factor beta receptor 1 or 2), the SMAD2 or SMAD3 genes (mothers against decapentaplegic homolog 2 or 3) or the TGFB2 or TGFB3 genes (tgfbeta 2 or 3, or transforming growth factor beta 2 or 3 ligand).
These genes encode for the receptors and other molecules involved in the tgf-beta pathway. Correlation between the genetic cause of LDS and physical manifestation continues to evolve.
There are five genetic causes of Loeys-Dietz syndrome, with the proposed naming system.
- Loeys-Dietz syndrome 1 caused by mutations in the TGFBR1 gene
- Loeys-Dietz syndrome 2 caused by mutations in the TGFBR2 gene
- Loeys-Dietz syndrome 3 caused by mutations in the SMAD3 gene
- Loeys-Dietz syndrome 4 caused by mutations in the TGFB2 gene
- Loeys-Dietz syndrome 5 caused by mutations in the TGFB3 gene
There is not yet enough information on LDS features caused by SMAD2 variants to include this gene in the list of Loeys-Dietz syndrome subtypes.
Although there is significant overlap between the clinical features caused by mutations in the different genes, we are learning about what might be differing features between the types and how this may impact medical management.
The term genetic disorder also indicates that the disorder has been present in an individual since conception. Loeys-Dietz syndrome exhibits an autosomal dominant inheritance pattern. This means that each offspring of an individual with LDS has a 50% chance of inheriting the gene mutation for LDS. There is no way to predict the severity of vascular, skeletal or skin findings that may occur in an offspring.
Many individuals are the first in their family to have the mutation causing LDS. These cases are caused by sporadic (random) mutations that occur during conception. There is no parental cause (medication or alcohol use for example) for the random mutation occurring. It is no one's fault.
For anyone who has the diagnosis of LDS and who is of reproductive age, it is recommended that they review the recurrence risk information with a genetics professional. There are testing options performed during pregnancy (prenatal diagnosis) and through in-vitro techniques (pre-implantation genetic diagnosis) to determine the presence of LDS in the fetus.
Last Updated February 7, 2020