Variability in the phenotypic expression of Fryns syndrome: A report of two sibships

We report on two sibships with four fetuses of 12, 15, 17, and 20 weeks of gestation, respectively, and 1 preterm baby of 31 weeks of gestation affect ed by a multiple congenital disorder with manifestation suggestive of Fryns syndrome. In addition to the characteristic malformation pattern in Fryns syndrome, they presented with fetal hydrops, cystic hygroma, and multiple p teryglas, allowing prenatal ultrasound diagnosis as early as in the 11th we ek of gestation, The two affected fetuses of family 1 showed severe craniof acial anomalies with bilateral cleft lip and palate, acral hypoplasia, post axial oligodactyly, persistent truncus arteriosus, and interrupted aortic a rch, asplenia sequence, and complex central nervous system midline malforma tions, In family 2 with three affected sibs, ear anomalies with atresia of the auditory canals, postaxial hexadactyly, intestinal atresias, callosal d efects, and eye colobomas were the most outstanding features. On the basis of the present findings and former reports, the inter-and intrafamiliar phe notypic variability in Fryns syndrome, possible pathogenetic mechanisms, an d the value of prenatal diagnosis are discussed. In the pathogenetic discus sion, a special emphasis is put on the neural crest cell developmental fiel d.