Which are the causes of Freeman Sheldon Syndrome?

Freeman Sheldon Syndrome, also known as whistling face syndrome, is a rare genetic disorder that affects various parts of the body. It is characterized by a distinct facial appearance, joint contractures, and other physical abnormalities. The exact cause of Freeman Sheldon Syndrome is not yet fully understood, but it is believed to be primarily caused by mutations in the MYH3 gene.

The MYH3 gene provides instructions for making a protein called myosin, which is involved in muscle contraction and movement. Mutations in this gene can disrupt the normal development and functioning of muscles, leading to the characteristic features of Freeman Sheldon Syndrome.

Genetic mutations can occur spontaneously or be inherited from a parent who carries the mutated gene. In most cases, Freeman Sheldon Syndrome is inherited in an autosomal dominant manner, which means that a person only needs to inherit one copy of the mutated gene from either parent to develop the condition. However, some cases may result from new mutations in the MYH3 gene.

The specific effects of MYH3 gene mutations on muscle development and function are not fully understood. However, it is thought that these mutations disrupt the normal balance of muscle contraction and relaxation, leading to the characteristic joint contractures seen in Freeman Sheldon Syndrome. Joint contractures are permanent tightening of the joints, which restricts movement and can cause significant functional impairment.

In addition to joint contractures, individuals with Freeman Sheldon Syndrome often have a distinctive facial appearance. This includes a whistling-shaped mouth, a small jaw, a prominent forehead, and a flat nasal bridge. These facial features are thought to result from abnormal muscle development in the face and skull during embryonic development.

Other physical abnormalities associated with Freeman Sheldon Syndrome may include clubfoot, webbed fingers or toes (syndactyly), shortened limbs, curvature of the spine (scoliosis), and abnormalities of the hands and feet. The severity of these features can vary widely among affected individuals.

While the exact cause of Freeman Sheldon Syndrome is still being researched, the identification of the MYH3 gene mutations has provided valuable insights into the underlying mechanisms of the condition. Further studies are needed to fully understand how these mutations lead to the specific features and symptoms of Freeman Sheldon Syndrome.