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Fraser syndrome
Fraser syndrome is a rare, potentially fatal developmental disorder characterized by eye malformations, fused digits, and genitourinary abnormalities.
Overview
Fraser syndrome affects development before birth. The most characteristic feature is cryptophthalmos, where the eyes are completely covered by skin and often malformed. The severity of the syndrome varies; while it can be fatal before or shortly after birth, some individuals survive into childhood or adulthood.
Symptoms
- Eyes: Cryptophthalmos (eyes covered by skin), microphthalmia (small eyes), or anophthalmia (missing eyes), leading to vision impairment or loss.
- Hands and Feet: Cutaneous syndactyly (fusion of skin between fingers and toes).
- Genitourinary: Renal agenesis (absence of one or both kidneys), bladder abnormalities, and genital anomalies (e.g., undescended testes or ambiguous genitalia).
- Other: Heart malformations, respiratory tract abnormalities, and facial features such as cleft lip or palate.
Causes
Mutations in the FRAS1, FREM2, or GRIP1 genes cause Fraser syndrome. These genes produce proteins that form the FRAS/FREM complex, which is found in basement membranes that support tissues. This complex acts as an anchor for the top layer of skin. When the complex is absent, the top layer of skin detaches during development, causing blisters that impair the formation of structures like the eyes and digits. The exact mechanism by which this leads to kidney and genital abnormalities remains unclear.
Inheritance
Fraser syndrome is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell must have mutations. Parents of an affected individual are typically carriers who do not exhibit signs or symptoms of the condition.