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Case Reports
. 2025 Nov 1:e64292.
doi: 10.1002/ajmg.a.64292. Online ahead of print.

An Uncommon Case of Hypophosphataemia-Non-Lethal Raine Syndrome With Novel FAM20C Variant: Expanding the Phenotypic Spectrum

Candice Wai-Man Au  1 , Shirley Sze-Wing Cheng  1 , Timothy Hua-Tse Cheng  2 , Pui Kwan Joyce Chan  3 , Lai-In Ho  4 , Jenny Yeuk-Ki Cheng  2 , Walter Wai Yeung  2 , Min Ou  1 , Vincent Cheuk-Tung Tse  5 , Hugo Chi-Chung Wong  5 , Ho-Ming Luk  1
Affiliations
Case Reports

An Uncommon Case of Hypophosphataemia-Non-Lethal Raine Syndrome With Novel FAM20C Variant: Expanding the Phenotypic Spectrum

Candice Wai-Man Au et al. Am J Med Genet A. .

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.

Keywords: FAM20C; FGF23; amelogenesis imperfecta; hypophosphataemia; non‐lethal Raine Syndrome; osteosclerosis.

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References

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