Updated 2006-01-18 by Juliana Leite, MD
Original text 1999-05-21 Philippe Jeanty, MD, PhD & Sandra R Silva, MD
Definition: Fryns syndrome is a rare congenital disorder characterized by dysmorphic facial features (coarse face with microphthalmia, hypertelorism, facial hair growth, cloudy corneas, broad and flat nasal bridge, cleft lip and/or palate, microretrognathia, and low-set ears), diaphragmatic hernia, distal limb hypoplasia and pulmonary hypoplasia. The first description was done by Fryns in 1979.
Incidence: Unknown. Ayme and coworkers reported a prevalence of 0.7:10,000 births in France.
Etiology:Autosomal recessive inheritance.
Recurrence risk: 25%.
Diagnosis: The phenotypic variability makes the sonographic diagnosis of Fryns syndrome a challenge. The detection of typical facial dysmorphism associated with diaphragmatic hernia (which is a leading sonographic criterion), hypoplastic thorax with widely spaced nipples, hypoplasia or absence of the lobulation of the lungs, distal limb deficiencies with hypoplasia of the terminal phalanges and nails, and postaxial oligodactyly should suggest Fryns syndrome(1). Development of polyhydramnios late in the second trimester and normal growth or overgrowth of the fetus are also expected. The use of three-dimensional ultrasound may be helpful to precisely define the facial anomalies. Although the frequency of cystic hygroma is not as high as the features mentioned above, this defect has been proposed as a sonographic first trimester marker for recurrent cases. Other findings that can be detected are persistent truncus arteriosus, and interrupted aortic arch, left isomerism, complex central nervous system midline malformations and multiple pterygias (1). Maternal and amniotic fluid alpha-fetoprotein levels may be elevated, in particular in fetuses that carry open defects.
Genetic anomalies: No specific DNA defect has been identified.
Differential diagnosis: The differential diagnosis includes trisomy 18 (which can be excluded by karyotype), Killian/Teschler-Nicole syndrome (mosaic tetrasomy 12p), Zellweger syndrome (deficiency of peroxisomal enzyme), and Brachman-DeLange syndrome (usually associated with severe growth restriction).
Associated anomalies: Anomalies from skeletal, cardiac, central nervous, gastrointestinal, and genitourinary systems can be associated with Fryns syndrome.
Prognosis: The majorities are stillborn or die in early neonatal period. A few reported survivals have severe mental and developmental retardation.
Management: When the syndrome is detected before viability, termination of pregnancy can be offered. After viability, standard prenatal care is not altered.
1: Ramsing M, Gillessen-Kaesbach G, Holzgreve W, Fritz B, Rehder H. Variability in the phenotypic expression of Fryns syndrome: A report of two sibships. Am J Med Genet 2000;95(5):415-24