Fraser syndrome is a rare congenital disorder characterized by cryptophthalmos and syndactyly. Ophthalmic features are very common among affected individuals and these include the lack of palpebral fissures with severe microphthalmia or anophthalmia, and absent or malformed lacrymal ducts. In addition to syndactyly, Fraser syndrome can involve severe malformations affecting the urinary system (e.g. renal agenesis or hypoplasia), larynx (stenosis, atresia), ears, palate, nose, tongue, and reproductive organs. This syndrome is not usually associated with intellectual impairment and it is most common in families with a history of consanguinity.
Antenatal diagnosis using ultrasonography is possible at 18 weeks gestation and the presence of 2 of the following features is required for diagnosis; microphthalmia, syndactyly, enlarged echogenic lungs, or oligohydramnios. Almost 25% of affected fetuses are stillborn and 20% die within the first year of life
Mutations in the FRAS1 gene is associated with Fraser syndrome 1. Fraser syndrome 2 and Fraser syndrome 3 are caused by mutations in FREM2 gene and GRIP1 gene, respectively.
The first report of bladder pseudoexstrophy in association with Fraser Sydrome was made by Daia (2001). The case was a 1-year old girl with the typical features of Fraser Syndrome, including cryptophthalmos and depressed broad nasal bridge, sydactyly of both hands and feet, and laryngeal stenosis. In addition, the patient had multiple urogenital abnormalities, including clitorimegaly and left renal agenesis. She also showed certain skeletal and abdominal wall abnormalities that are usually associated with a bladder extrophy, such as a herniated bladder, a low-set umbilicus, and separated pubic bones. However, the bladder was intact, prompting Daia (2001) to term it a pseudoexstrophy.
van Haelst et al. (2008) studied 48 Fraser syndrome patients from 18 consanguineous and 15 non-consanguineous families. DNA analysis revealed a homozygous c.9524A>C mutation in the FRAS1 gene in one Emirati.