Myhre syndrome

Signs and symptoms

The clinical presentation is variable but includes

The facial abnormalities include:

The skeletal abnormalities include:

Congenital heart disease and undescended testes have also been reported in association with this syndrome.

Genetics

It is inherited as an autosomal dominant disorder.

It is due to mutations in the SMAD4 gene. This gene encodes a protein - transducer mediating transforming growth factor beta. Some researchers believe that the SMAD4 gene mutations that cause Myhre syndrome impair the ability of the SMAD4 protein to attach (bind) properly with the other proteins involved in the signaling pathway. Other studies have suggested that these mutations result in an abnormally stable SMAD4 protein that remains active in the cell longer. Changes in SMAD4 binding or availability may result in abnormal signaling in many cell types, which affects development of several body systems and leads to the signs and symptoms of Myhre syndrome.

The patients of this disease exhibit hypertrophic phenotype in their muscle tissues. Myostatin target genes are found to be downregulated while bone morphogenetic protein (BMP) target genes display both upregulated and downregulated genotypes.

History

This disorder was first reported in 1981. It has much similarity to LAPS Syndrome and they are both from the same mutations in the SMAD4 gene. It is now believed by many that they are the one in the same syndrome.