Fryns syndrome

Fryns syndrome is a rare, severe multiple congenital anomaly syndrome first described by Fryns et al. in 1979. It is characterized primarily by congenital diaphragmatic hernia (CDH), which is present in approximately 80-90% of affected individuals, along with distal limb hypoplasia (underdeveloped fingernails and toenails, short fingers), characteristic facial features, and pulmonary hypoplasia (underdeveloped lungs). The facial features typically include a coarse face, wide and flat nasal bridge, thick nasal tip, long philtrum, low-set ears, and a wide mouth with a thick lower lip. Additional findings may include cloudy or opaque corneas, cardiovascular malformations, renal anomalies (such as cystic kidneys or renal agenesis), gastrointestinal malformations, and central nervous system abnormalities including Dandy-Walker malformation and agenesis of the corpus callosum. Polyhydramnios is frequently observed during pregnancy. Fryns syndrome affects multiple organ systems including the respiratory, cardiovascular, gastrointestinal, genitourinary, musculoskeletal, and central nervous systems. The prognosis is generally very poor, with the majority of affected infants dying in the neonatal period or being stillborn, primarily due to severe pulmonary hypoplasia associated with the diaphragmatic hernia. However, rare long-term survivors have been reported, typically those with less severe diaphragmatic defects. In survivors, intellectual disability is commonly observed. The exact genetic cause of Fryns syndrome remains unknown in most cases, though it follows an autosomal recessive inheritance pattern. No specific gene has been definitively identified, although some chromosomal abnormalities have been reported in association. Treatment is primarily supportive and surgical, focusing on repair of the diaphragmatic hernia and management of associated anomalies. Prenatal diagnosis may be possible through ultrasound detection of diaphragmatic hernia and other characteristic features. Genetic counseling is recommended for affected families given the 25% recurrence risk in subsequent pregnancies.

Common questions about Fryns syndrome