Alerts and Notices
SynopsisFraser syndrome (FS), also known as cryptophthalmos-syndactyly syndrome, is a rare autosomal recessive condition affecting approximately 1 in 200 000 newborns. FS arises from mutations in the FRAS1 (approximately 50% of cases), FREM1, FREM2, or GRIP1 genes, which cause failure of apoptotic processes during embryogenesis and defects in connective tissue development. The condition affects males and females equally. It is reportedly more prevalent in the Roma populations of southern and eastern Europe.
FS is characterized by unilateral or bilateral cryptophthalmos (skin covering the eyes), with or without underlying abnormalities of the eye; syndactyly (fused digits of the hands and feet); renal agenesis; and genital anomalies such as cryptorchidism and ambiguous genitalia. Less common abnormalities include heart malformations, anomalies of the larynx and respiratory tract, and cleft lip / palate. The condition can be fatal in the antenatal and neonatal periods, but individuals with lower severity of symptoms can live into childhood or adulthood with a normal life expectancy.
The prognosis depends on the severity of the condition. Death within the first year of life is common in affected newborns with severe anomalies.
Q87.0 – Congenital malformation syndromes predominantly affecting facial appearance
204102004 – Cryptophthalmos syndrome
Differential Diagnosis & Pitfalls
- Trigonocephaly 2 – FREM1 gene mutation resulting in intellectual disability and a triangular head.
- Manitoba oculotrichonal syndrome – FREM1 gene mutation resulting in a bifid nose, hypertelorism, and microphthalmia.
- Cat eye syndrome – Characterized by ocular coloboma, anal atresia, ear abnormalities (typical triad), with or without renal agenesis, cardiac defects, intellectual disability, etc.
- Fryns syndrome – Characterized by congenital diaphragmatic defects (> 90% of affected individuals), pulmonary hypoplasia, microphthalmia, orofacial clefting, distal digital hypoplasia, cardiac malformations, GI malformations, renal dysplasia / cysts, genital malformations, etc.
- CHARGE syndrome – Coloboma, heart defects, atresia of the choanae, retardation of growth, genital underdevelopment, ear abnormalities.
- Meckel syndrome – Occipital encephalocele, cystic kidneys, craniofacial abnormalities, polydactyly, pulmonary hypoplasia due to oligohydramnios, GI tract abnormalities, etc.
- Norrie disease – X-linked eye disorder characterized by blindness at birth due to abnormal retinal development.
- Syndromic microphthalmia-9 (MCOPS9) – Autosomal recessive disorder characterized by bilateral clinical anophthalmia, pulmonary hypoplasia, cardiac abnormalities, and diaphragmatic defects.
- Branchiootorenal spectrum disorders – Characterized by hearing loss and renal agenesis.
- Bilateral renal agenesis – Due to failure of kidneys to develop in utero.