Fraser syndrome is a rare genetic disorder characterized by fused eyelids (cryptophthalmos), fusion of the skin between the fingers and toes (syndactyly), and abnormalities of the genitalia and urinary tract. Signs and symptoms occur early in development and may also include abnormalities of the respiratory tract, specifically involving the larynx (voice box) and trachea (windpipe); failure of kidney development affecting one or both kidneys (renal agenesis); umbilical hernia; abnormalities of the nose and ear; cleft lip and palate; skeletal abnormalities; and intellectual disability. Depending on the severity of the signs and symptoms, Fraser syndrome can be fatal before or shortly after birth. Less severely affected individuals can live into childhood or adulthood.

Fraser syndrome is caused by mutations in three different genes: FRAS1, GRIP1, and FREM2 and is inherited in an autosomal recessive manner. This condition is diagnosed based on signs and symptoms. Genetic testing may be useful to confirm the diagnosis. While there is no cure for Fraser syndrome, there may be ways to manage symptoms, depending on the severity. A team of doctors is often needed to figure out the treatment options for each person.

FRAS1, GRIP1, and FREM2. The FRAS1 and FREM2 genes codes for proteins that work together and are involved in the proper development of the skin, internal organs, and other tissues. The GRIP1 gene codes for the GRIP1 protein, which ensures that the FRAS1 and FREM2 proteins get to the correct location of the cell to work together. Mutations in these genes are thought to impair the ability of the FRAS1 and FREM2 proteins, resulting in abnormal development of certain organs and tissues before birth.

FRAS1, GRIP1, or FREM2) in each cell. Individuals with Fraser syndrome inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected) and often do not know they are carriers until they have an affected child. When 2 carriers of an autosomal recessive condition have children, each child has a:

• 25% chance to be affected
• 50% chance to be an unaffected carrier like each parent
• 25% chance to be unaffected and not a carrier

Genetic testing may additionally be useful to confirm the diagnosis.

At this time, there is no cure for Fraser syndrome. Treatment varies depending on the severity of symptoms present in each individual. Some malformations may be corrected with surgery. A team of specialists is needed to evaluate each individual and determine what methods can be used to manage or treat each symptom.

The long-term outlook (prognosis) for Fraser syndrome differs depending on the severity of the signs and symptoms present. Fraser syndrome can be fatal before or shortly after birth in approximately 40% of cases. Abnormalities of the central nervous system, larynx (voice box) and pharynx (windpipe); absent or underdeveloped kidneys; and respiratory insufficiency may lead to a poor prognosis. In the absence of these findings, individuals may have a normal life span.