Fryns syndrome is a multiple congenital anomaly syndrome characterized by dysmorphic facial features, congenital diaphragmatic hernia (CDH; see this term), pulmonary hypoplasia, and distal limb hypoplasia in addition to variable expression of additional malformations.
The birth prevalence of FS has been estimated at 1/14,000 births.
Polyhydramnios is often noted during pregnancy and neonates present with a spectrum of various malformations at birth. The classical features of FS include CDH (unilateral in 75% of cases), dysmorphic craniofacial features (coarse facies, ocular hypertelorism, microphthalmia, low-set, poorly formed ears, a broad and flat nasal bridge, thick nasal tip with anteverted nares, long philtrum, tented upper lip, macrostomia and microretrognathia) and limb malformations (mainly distal limb hypoplasia that includes short and broad hands, short digits, short terminal phalanges, hypoplastic or absent nails and clinodactyly). Thorax is small with widely spaced nipples. Brain (ventricular dilation, hydrocephalus) and cardiac malformations (atrial and ventricular septal defects (see these terms), aortic abnormalities) are reported frequently in affected individuals. Additional anomalies include orofacial clefting as well as pulmonary (lung hypoplasia), gastrointestinal (malrotation, anal atresia, omphalocele (see this term)), uro-genital (renal cysts, ureteral dilation, cryptorchidism), and musculo-skeletal (talipes, broad clavicles) malformations. In those that survive the neonatal period, severe developmental delay and intellectual disability is common. Death is mainly due to complications of CDH and pulmonary hypoplasia.
The etiology is not clear. Several chromosomal aberrations including microdeletions involving chromosome bands 15q26.2 and 8p23.1 have been reported in probands with FS but the causal genes are yet to be identified.
Diagnosis is based purely on clinical findings (CDH with brachytelephalangy, nail hypoplasia, craniofacial dysmorphism, pulmonary hypoplasia and/or polyhydramnios) as the causal gene has not yet been identified. Array comparative genomic hybridization (array CGH) can be useful in differentiating FS from other chromosomal conditions with CDH, as FS is associated with a normal karyotype. Radiographs, ultrasounds, echocardiograms, and magnetic resonance imaging (MRI) may be necessary to identify all anomalies present.
Differential diagnosis includes Donnai-Barrow syndrome, Matthew-Wood syndrome, Simpson-Golabi-Behmel syndrome, Cornelia de Lange syndrome, tetrasomy 12p, distal monosomy 15q (see these terms) and other chromosome aberrations.
Prenatal diagnosis is possible, in couples with a previously affected child, by 3D ultrasonography and fetal MRI revealing the characteristic malformations. Exclusion of chromosomal abnormalities and gene mutations is needed prior to diagnosis.
FS is thought to be inherited as an autosomal recessive trait and genetic counseling is possible in those with a family history of the disease.
Management of FS is multidisciplinary and may necessitate pediatric specialists in neurology, cardiology, gastroenterology and nephrology as well as clinical geneticists, developmental pediatricians and regular follow-up in a specialized centre. Supportive treatments are directed at the management of the diaphragmatic hernia and include extra-corporeal membrane oxygenation (ECMO) and nitric oxide and surfactant as therapies for persistent pulmonary hypertension of the newborn (PPHN). Other malformations are managed with standard treatment procedures.
Prognosis depends on malformations present, but is usually poor with survival beyond the neonatal period being rare. Patients without diaphragmatic defects have a better prognosis.
Last update: December 2014