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

Abstract

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 affected 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 pterygias, allowing prenatal ultrasound diagnosis as early as in the 11th week of gestation. The two affected fetuses of family 1 showed severe craniofacial anomalies with bilateral cleft lip and palate, acral hypoplasia, postaxial oligodactyly, persistent truncus arteriosus, and interrupted aortic arch, asplenia sequence, and complex central nervous system midline malformations. In family 2 with three affected sibs, ear anomalies with atresia of the auditory canals, postaxial hexadactyly, intestinal atresias, callosal defects, and eye colobomas were the most outstanding features. On the basis of the present findings and former reports, the inter- and intrafamiliar phenotypic variability in Fryns syndrome, possible pathogenetic mechanisms, and the value of prenatal diagnosis are discussed. In the pathogenetic discussion, a special emphasis is put on the neural crest cell developmental field.

Fryns syndrome: Report of eight new cases

“…7 Hirschsprung disease results from aberrant migration of neural crest cells and this case supports the hypothesis that aberrant neural crest cell migration may be pathogenically important in at least some cases with FS. 8 Further support for the importance of aberrant neural crest cell mi- Letters to the editor gration comes from cardiac malformations consistent with abnormal cardiac neural crest cell migration in FS, such as Tetralogy of Fallot and interrupted aortic arch.…”

Fryns Syndrome in Monozygotic Twins: A Case Report with Review of Literature

“…However, no specific genetic change has been found to cause all of the signs and symptoms of this disorder. A significant inter and intra-familial phenotypic variability as well as discordant phenotype in monozygotic twins has been reported (Ramsing et al, 2000;Vargas et al, 2000).…”

A system‐based approach to the genetic etiologies of non‐immune hydrops fetalis

“…CPAMs have not been reported as part of specific genetic disorders, but the genes HOXB‐5 , FGF‐7 , and PDGFB have been implicated in their development . CDH is associated with NIHF in a number of genetic disorders, including Pallister‐Killian syndrome, Fryns syndrome, and deletions such as 1p21.1p12 . CHAOS has been reported with NIHF and an underlying diagnosis of v ertebral defects, a nal atresia, c ardiac defects, t racheo‐ e sophageal fistula, r enal anomalies, and l imb abnormalities (VACTERL) association, as well as with several rare genetic disorders .…”

“…Genetic disorders by organ system Fryns syndrome, and deletions such as 1p21.1p12 45,46,129. CHAOS has been reported with NIHF and an underlying diagnosis of vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities (VACTERL) association, as well as with several rare genetic disorders 44,130.…”