A multidisciplinary approach for prenatal diagnosis of FRASER SYNDROME-report of a novel variant in FRAS1.

OBJECTIVE: With this case report, we would like to highlight the importance of a multidisciplinary approach and atypical findings of congenital high airway obstruction sequence (CHAOS), anhydramnios, and renal dysgenesis in the prenatal diagnosis of Fraser syndrome (FS). CASE REPORT: A 25-year-old primigravida at 19 weeks of routine anomaly scan revealed abnormal sonographic findings such as fetal bilateral dysplastic small kidneys and gross oligohydramnios. The further detailed evaluation revealed that both fetal lungs were hyperechogenic with prominent (dilated) trachea and bronchi suggestive of CHAOS. Based on these findings, a diagnosis of FS was suspected. The couple was counseled and the pregnancy was terminated. The postmortem evaluation and novel homozygous variant in the FRAS1 gene confirmed the diagnosis of FS. CONCLUSION: The diagnosis and counseling of the patient were supported by a well-coordinated, multidisciplinary approach involving an obstetrician, a fetal medicine specialist, a medical geneticist, and a fetal pathologist.

Fraser syndrome: review of the literature illustrated by a historical adult case.

Fraser syndrome (cryptophthalmos-syndactyly syndrome) is a rare autosomal recessive malformation disorder. The first description of the syndrome was reported by George Fraser in 1962. Diagnosis is based on the major and minor criteria established by van Haelst et al. in 2007. Unilateral or bilateral cryptophthalmos, syndactyly, unilateral renal agenesis, and genital anomalies are the most frequent anomalies. Several maxillofacial, oro-dental, ear-nose-throat, hormonal, and anorectal disorders are reported. Cardiac malformations and musculoskeletal anomalies are uncommon. The syndrome is related to mutations in three different genes (FRAS1, FREM2, and GRIP1) resulting in failure of the apoptosis program and disruption of the epithelial-mesenchymal interactions during embryonic development. Prenatal diagnosis is based on the detection of renal agenesis and laryngeal atresia, together with a family history. Most foetuses with severe anomalies are terminated or are stillborn. All patients or pregnancies with a diagnosis of Fraser syndrome should be referred to expert centres. A collaborative approach including anaesthetists, ENT specialists, maxillofacial surgeons, and geneticists is necessary for the management of this syndrome. In vivo and in vitro research models are available to better understand the underlying aetiology.

Fraser syndrome: features suggestive of prenatal diagnosis in a review of 38 cases.

OBJECTIVE: Fraser syndrome (FS) is a rare malformation recessive disorder. Major criteria are cryptophtalmos, syndactyly, respiratory, genital and urinary tract anomalies. Few prenatal presentations have been reported. METHOD: We analyzed the prenatal and postnatal fetal phenotype in 38 cases of FS, including 25 pregnancy termination cases, 8 intra-uterine death cases and 4 cases that died after birth. RESULTS: Including both prenatal and postnatal fetal phenotypic evaluation, all cases presented dysmorphic features with nose and ear dysplasia. Renal anomalies and syndactyly were present in 37/38 cases, cryptophtalmos in 36/38, airways anomalies in 30/37 and genital anomalies in 30/35 cases. Anomalies of the abdominal wall such as low set umbilicus and omphalocele were found in 31 cases. Among the 26 cases for which ultrasound data were available, detectable anomalies included oligohydramnios (22), ascites/hydrops (9), renal anomalies (20), evidence for high airways obstruction (11), ophthalmologic anomalies (4), ear dysplasia (2) and syndactyly (2). CONCLUSION: This study shows that the postnatal phenotype of FS is very specific, whereas oligohydramnios hampers the prenatal recognition of the cardinal FS diagnosis criteria. Association of oligohydramnios, kidney agenesis and CHAOS should lead to consider this diagnosis. © 2016 John Wiley & Sons, Ltd.