Atypical Presentation of Raine Syndrome in a Middle-aged Lady

Area of Science:

• Genetics
• Biochemistry
• Radiology

Background:

• Raine syndrome is a rare autosomal recessive disorder characterized by osteosclerotic bone dysplasia, often fatal in neonates.
• Mutations in the FAM20C gene, encoding a key enzyme in bone mineralization, cause Raine syndrome and FGF23-mediated hypophosphatemic rickets/osteomalacia.
• Nonlethal variants of Raine syndrome have been identified, suggesting a broader clinical spectrum.

Purpose of the Study:

• To report a novel homozygous FAM20C mutation in an adult patient with Raine syndrome.
• To expand the understanding of the phenotypic and genetic spectrum of nonlethal Raine syndrome variants.
• To investigate the clinical presentation of adult-onset Raine syndrome with hypophosphatemic osteomalacia.

Main Methods:

• Clinical evaluation of a middle-aged female presenting with proximal myopathy.
• Biochemical analysis to assess phosphate levels and renal tubular wasting (TMP/GFR).
• Radiological assessment for osteomalacia and osteosclerosis.
• Molecular analysis to identify mutations in the FAM20C gene.

Main Results:

• The patient presented with proximal myopathy, hypophosphatemia, and renal tubular phosphate wasting.
• Radiological findings were suggestive of osteomalacia and osteosclerosis.
• A novel homozygous FAM20C mutation (c.1375C>T; p.Arg459Cys) was identified, confirming the diagnosis of Raine syndrome.

Conclusions:

• This case expands the phenotypic spectrum of Raine syndrome to include adult-onset proximal myopathy and hypophosphatemic osteomalacia.
• The identification of a novel FAM20C mutation further contributes to the genetic understanding of nonlethal Raine syndrome variants.
• FAM20C mutations can lead to diverse clinical presentations, including those manifesting in adulthood.