Am J Med Genet A. 2025 Nov 1:e64292. doi: 10.1002/ajmg.a.64292. Online ahead of print.
ABSTRACT
Raine Syndrome (MIM #259775) is an autosomal recessive osteosclerotic disorder due to biallelic variants in the FAM20C gene. It is classified into two subtypes based on perinatal lethality. Here, we report an 18-year-old male who presented with dental problems in childhood and subjective gait instability, followed by an incidental finding of hypophosphataemia and multiple-level spinal stenosis. Examination showed characteristic features including a high forehead, midface hypoplasia, prognathism, amelogenesis imperfecta, brachydactyly and bulbous finger tips, and further biochemical workup revealed a low 1,25-dihydroxyvitamin D level and an elevated FGF23 level. Exome sequencing identified compound heterozygous NM_020223.4 c.1487C > T, p.(Pro496Leu), and c.1375C > T, p.(Arg459Cys) likely pathogenic variants in the FAM20C gene, with the latter being a novel variant. This case report therefore expands the genetic and phenotypic spectrum of non-lethal Raine Syndrome, and underscores the importance of genetic evaluation in hypophosphatemic patients with dysmorphic features.
PMID:41174912 | DOI:10.1002/ajmg.a.64292
