Raine syndrome: Report of a novel mutation and review of the different antenatal imaging modalities used to diagnose this disease

Abstract

Introduction Raine syndrome is an autosomal recessive disorder characterized mainly by the presence of exophthalmos, choanal atresia or stenosis, osteosclerosis, and cerebral calcifications. There are around 50 cases described in the literature with a prevalence of less than 1/1,000,000. It is secondary to pathogenic variants in the FAM20 C gene, located on chromosome 7p22.3. Case report We report a consanguineous family with three affected pregnancies. In the first two, exophthalmos and bone abnormalities were noted, ending in one intra‐uterine demise and one neonatal death, without identifying any genetic disorder. During the couple's most recent pregnancy, fetal anomaly sonogram and fetal CT scan revealed microcephaly, intracranial calcifications, exophthalmos, hypertelorism, depressed nasal bridge, midface hypoplasia and thoracic hypoplasia. Fetal blood sampling for whole exome sequencing revealed a novel pathogenic homozygous variant c.1363+1G > A in the FAM20 C gene associated with Raine syndrome. Delivery occurred at 26 weeks of gestation after rupture of membranes followed by neonatal death due to respiratory failure. Review A review of the distinctive features of Raine syndrome, the contribution of different prenatal imaging modalities (Ultrasound, Computed Tomography and Magnetic Resonance Imaging) in making the diagnosis and the molecular characterization of this disorder is provided.

Compound heterozygous FAM20C gene variants in a patient with severe Raine syndrome: a case report

“… Simpson et al (2009) were the first to report on non-lethal Raine syndrome when the patients were 9 and 11 years old. Approximately 70 cases of Raine syndrome (40 cases of lethal Raine Syndrome and 30 non-lethal cases) have been reported ( Xu, R., et al, 2021 ), with a prevalence of 1/100,000 cases, requiring continuous investigations to understand better the syndrome, its functioning mechanism, and possible treatment ( Rameh, G., et al, 2022 ). Raine et al described in 1989 an unknown multiple congenital anomalies syndrome in a newborn who died soon after birth, later on, identified as Raine Syndrome ( Hernández-Zavala, A., et al, 2020 ).…”

Prenatal sonographic phenotype of Raine syndrome: detection of novel FAM20C gene mutation at 20 weeks

“…Neonatal demise occurs due to respiratory distress as a consequence of choanal atresia or pulmonary hypoplasia in the lethal type. The characteristic facies of Raine syndrome comprises exophthalmos, hypertelorism, midfacial hypoplasia, a depressed nasal bridge, micrognathia and low-set ears 4,5 . Skeletal manifestations include frontal bossing with a cloverleaf-shaped skull, osteosclerosis, shortening of long bones, irregular bone contour due to fractures, periosteal bone formation and a narrow thorax 6 .…”