Fraser syndrome

Fraser syndrome (also known as cryptophthalmos-syndactyly syndrome) is a rare autosomal recessive congenital malformation disorder characterized by a distinctive triad of cryptophthalmos (hidden eyes due to skin covering the eyeball), syndactyly (fusion of the fingers and/or toes), and genitourinary anomalies. The condition is caused by mutations in the FRAS1, FREM2, or GRIP1 genes, which encode proteins involved in epithelial-basement membrane adhesion during embryonic development. The syndrome affects multiple organ systems. Ocular abnormalities are the hallmark feature and range from complete cryptophthalmos (where the eyelids fail to form and skin covers the eye) to partial cryptophthalmos or microphthalmia/anophthalmia. Cutaneous syndactyly, most commonly involving the fingers and toes, is present in the majority of affected individuals. Genitourinary malformations include renal agenesis or dysplasia, ambiguous genitalia, and malformations of the uterus or vagina. Additional features may include laryngeal or tracheal stenosis or atresia, which can be life-threatening in the neonatal period, as well as ear malformations, nasal anomalies, and intellectual disability in some cases. The prognosis of Fraser syndrome is variable and depends largely on the severity of the associated malformations. Bilateral renal agenesis and severe airway anomalies are the most common causes of stillbirth or early neonatal death, and a significant proportion of affected individuals are stillborn or die in infancy. For those who survive, management is supportive and multidisciplinary, involving ophthalmologic, surgical, urologic, and otolaryngologic care. Surgical correction of syndactyly and reconstruction of eyelids may be performed when feasible. Genetic counseling is recommended for affected families, as carrier parents have a 25% recurrence risk with each pregnancy.

Common questions about Fraser syndrome