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.