Fraser syndrome is a rare genetic disorder that causes malformations in several parts of the body. It can be very serious and sometimes life-threatening, but individuals with less severe symptoms can manage their symptoms and may have a normal lifespan. Fraser syndrome has many other names, including Meyer-Schwickerath syndrome, Fraser-Francois syndrome, and Ullrich-Feichtiger syndrome.
Definition & Facts
The condition was named after George Fraser, the geneticist who discovered it in the 1960s. The symptoms vary from person to person, but almost all individuals with the syndrome have eyelids which are fused together and cannot separate.
The severity of the symptoms also vary, and the syndrome is fatal before or shortly after birth in about 40 percent of cases. If an individual has less severe symptoms, he or she can live to adulthood. Fraser syndrome occurs in about 1 in 200,000 newborns and in about 1 in 10,000 fetuses who don't make it to birth. The condition affects men and women equally, but it is most common in individuals from southern and eastern Europe.
Symptoms & Complaints
Beneath the fused eyelids, the eyes also may be malformed. The eyes themselves sometimes fuse to the eyelids or may be abnormally small or missing. Vision impairment or blindness are common in individuals with Fraser syndrome.
Many individuals with the condition have syndactyly, or the fusion of the fingers or toes. Usually, the three middle fingers or toes are fused together, but the outer fingers and toes are sometimes connected as well.
Other common symptoms of the syndrome include malformations of the ears, nose, larynx, genitals, kidneys, and urinary system. The condition sometimes causes one or both kidneys to be missing. Occasionally, people with Fraser syndrome also have congenital heart defects, and some have intellectual disabilities.
Fraser syndrome is a genetic condition, so it is always caused by a genetic mutation. In about half of cases, it is linked to the FRAS1 gene, and in other cases, it is linked to the FREM2 gene and GRIP1 gene.
The FRAS1 and FREM2 genes belong to the FRAS/FREM complex, which are a group of proteins that support a variety of tissues throughout the body. This complex is very important during fetal development, and issues with the complex can result in malformations. The FRAS/FREM complex is partially responsible for the development of the kidneys and other organs and for connecting the top layer of skin to the next layer.
When there is a mutation in the FRAS1 or FREM2 gene, the FRAS/FREM complex doesn't form properly, so the top layer of skin detaches. This leads to the formation of blisters, which prevent other structures from forming, resulting in cryptophthalmos and other malformations.
Fraser syndrome is an autosomal recessive inheritance disorder, so individuals with the condition have inherited the mutated gene from both parents. Both parents must be genetic carriers of one mutated FRAS1, FREM2, or GRIP1 gene. Because an individual needs two mutated genes for the syndrome to be present, there is a 25 percent chance a child will receive the mutated gene from each parent and have the disease.
Diagnosis & Tests
Doctors use physical examinations and the family's genetic history to diagnose Fraser syndrome. The presence of cryptophthalmos does not necessarily indicate Fraser syndrome. Doctors usually look for a combination of cryptophthalmos and other malformations of the face, hands, kidneys, or genitals.
Major criteria include cryptophthalmos, the fusion of the fingers or toes, malformations in genitalia, malformations in the larynx or trachea, and a family history of the syndrome. Minor criteria include malformations in the face, skeletal defects, kidney defects, and intellectual disability. To be diagnosed, individuals usually should have three major criteria, two major criteria and two minor criteria, or one major criteria and three minor criteria.
Fraser syndrome can often be diagnosed with a prenatal ultrasound if the syndrome is severe. Doctors can often make a diagnosis once the fetus is at 18 weeks if the fetus shows two criteria. Criteria for fetuses include oligohydramnios, or a low amount of amniotic fluid; microphthalmia, or abnormally small eyeballs; obstructive uropathy, or the inability for urine to drain through the ureter; and the fusion of the fingers or toes.
Treatment & Therapy
There is no cure for Fraser syndrome, but individuals can undergo treatment to address their symptoms. Some people with the condition can have surgery to correct malformations that occur as a result of the genetic mutation. This includes surgery to correct the eyelids, genitals, and facial malformations.
Symptoms vary in severity for everyone with the condition, so doctors and professionals have to determine the best treatment plan for an individual. Doctors can consider the severity of a patient's symptoms to determine whether he or she could benefit from a surgery to correct a malformation. If the symptoms aren't severe, people with Fraser syndrome can live to adulthood and have a normal lifespan. Many people with the syndrome seek other therapies, such as physical therapy or occupational therapy, to help with symptom management.
Prevention & Prophylaxis
A genetic counselor can help parents decide whether they want to have a child if they are both carriers. Early diagnosis or diagnosis during pregnancy can help the parents learn how severe the symptoms are and what treatment options are available.