Raine syndrome: Prenatally identified severe craniofacial phenotype with multisuture synostosis and brain abnormalities associated with variants in FAM20C

Raine syndrome (MIM 259775) is a rare autosomal recessive disorder, first described by Raine et al. in 1989, with an estimated prevalence of A (p.Gly482Glu)) was identified in FAM20C associated with Raine syndrome. The infant had the characteristic dysmorphic features seen in Raine syndrome. He had particularly significant CNS manifestations consisting of multisuture craniosynostosis with protrusion of the brain parenchyma through fontanelles and cranial lacunae. Histological sections of the brain showed marked periventricular gliosis with regions of infarction, hemorrhage, and cavitation with global periventricular leukomalacia. Numerous dystrophic calcifications were diffusely present. Here, we demonstrate the identification of a novel variant in FAM20C in an infant with the characteristic features seen in Raine syndrome. The patient expands the characteristic phenotype of Raine syndrome to include a uniquely severe CNS phenotype, first identified on prenatal imaging. Key points What is already known about this topic? Biallelic pathogenic variants in FAM20C are associated with Raine syndrome (OMIM #259775). Raine syndrome is characterized by diffuse, marked osteosclerosis of the base of the skull and long bones as well as typical dysmorphic features including proptosis, underdeveloped midface, depressed nasal bridge and short nose. What does this study add? A novel variant in FAM20C associated with the characteristic features seen in Raine syndrome. Demonstration that prenatal imaging is highly sensitive for the majority of characteristic anomalies in Raine syndrome. Expansion of the phenotype of Raine syndrome to include a uniquely severe CNS phenotype.