Современные возможности пренатальной и постнатальной диагностики синдрома Фринса: собственные наблюдения и обзор литературы

Fryns syndrome (FS, OMIM#194050) is a rare lethal autosomal recessive disorder with unknown genetic defect, manifested the distinct complex of the multiply congenital abnormalities (MCA), including diaphragmatic hernia. There was made the world literature overview for the FS phenotypic features, clinical and genealogical data of the published familial cases, ultrasound and morphological characteristics of affected fetuses. Aim . Analysis of the clinical, morphological and prenatal ultrasound data of 12 FS cases, detected in Belarus during 2009-2018 years, and families’ reproduction results. Material and methods . Genetic counseling of 10 families with affected outcome was performed. All the pregnants underwent the combined (biochemical and ultrasound) screening. Prenatal and postnatal cytogenetical studies (GTG-banding) and the morphological investigations of the 10 aborted fetuses and 2 deceased infants were fulfilled. Results and Discussion . All the patients presented typical FS phenotypic features correlated with the diagnostic criteria. The spectrum of prenatal findings diagnosed at 1-st trimester included nuchal skin enlargement/cystic hygroma (5 cases), at the 2-ed trimester – diaphragmatic hernia (11 cases), omphalocele (1), other malformations (4 fetuses). The facial dysmorphisms (coarse face) were detected in all the patients. Lungs hypoplasia was found in all cases, 5 patients additionally dysplayed other abnormalities: pulmonary sequestration, cystic-adenomatoid malformation, lobular aplasia. Characteristic phalanges and nails hypoplasia or aplasia were registered in 11 cases, 3 sibs presented rare malformations – polydactyly (hands) and ectrodactyly (feet). Associated malformations spectrum included cleft palate, brain abnormalities (ventricular dilatation, arhinencephaly), cardiac defects, omphalocele, Meckel diverticule, hydronephroses, renal cysts, bicornuate uterus and hypospadia. The familial case with 3 affected sibs demonstrated a similarity in main diagnostic criteria. The couples reproduction analysis illulustrated a serious failure. Outcome of 29 pregnancies were as follows: 12 – FS cases, 4 – miscarries at 1-st trimester, 11 – healthy offspring and 2 cases – pregnancies are going on currently (both fetuses without malformations). Conclusion . Clinical diagnosis of FS may be noted in patients (either fetuses or newborns), which display the conjunction of typical MCA pattern with a normal karyotype. Additional investigations must be used in order to exclude the associated abnormalities if diaphragmatic hernia has been detected in fetus. In our opinion polydactyly and ectrodactyly may be added to the FS phenotypic spectrum.