General Information
The SMAD4gene is found on the long arm of the chromosome 18 and has 11 coding regions (called exons). It makes a protein called Mothers against decapentaplegic homolog 4 (SMAD4), plays a role in the transformation growth factor-beta (TGFβ) signaling pathway, which helps control cell growth and development. Disruptions in this pathway are thought to contribute to the characteristics of Myhre Syndrome, affecting multiple systems, including the heart, skeleton, and skin.
How the Disease Happens
Research indicates that the enhanced function of SMAD4 protein causes the TGFβ pathway to become overactive, impacting the body's growth and development. There’s still some uncertainty about which mechanism is correct. However, there is still incomplete information about the disease mechanism.
Inheritance
Myhre Syndrome is an autosomal dominant disorder. It means that you only need one copy of a gene with a change (pathogenic variant) to get the condition. If one parent has the gene change, there’s a 50% chance they can pass it on to their child. Even if the parents don’t have the gene change, the child can still get the condition with the spontaneous pathogenic variant in the gene.
Diagnostic Testing
There are two approaches to detect the disease-causing changes in the SMAD4gene in Myhre Syndrome: If the individual’s traits suggest Myhre Syndrome, a direct DNA sequence analysis of the SMAD4gene will be sufficient. If the individual’s traits do not strongly suggest Myhre Syndrome, a multi-gene panel or whole exome sequencing will be used to analyze the DNA sequence of several genes, including SMAD4. Both of these genetic tests can be arranged by a clinical geneticist and require a blood sample from the affected individual (and possibly from the parents as well).
SMAD4