Background: Raine Syndrome (RS) is characterized by hypophosphatemia and typical facial dysmorphic features. Subperiostal thickening and diffuse generalized osteosclerosis are the most common radiological findings. Biallelic loss of function mutations in FAM20Cgene cause RS and by reduction of the transcription of DMP1 leads to FGF23-related hypophosphatemia. Here we present a new case with RS.
Case: A 9-month-old male patient on a home-type ventilator was referred for hypophosphatemia. He was born with a weight of 3800 gr to non-consanguineous parents. Prenatal USG demonstrated nasal bone agenesis.He had tracheostomy, percutaneous endoscopic gastrostomy and ventriculoperitoneal shunt operations at 48 days, 5.5 and 9 months of age, respectively. Family history was unremarkable. At presentation, his height, weight and head circumference were at -1.1, -2.14 and -0.62 SDS, respectively. A large anterior fontanel (5x6 cm), frontal bossing, exophthalmos, hypoplastic nose, high arched palate, low set ear, triangular mouth, and corneal opacification were detected on physical examination. The ophthalmological examination was consistent with optic atrophy.
On laboratory evaluation: Ca:9.6mg/dL (9-11), PO4:2.0mg/dL (4-6.5), ALP:950U/L (116-450), 25OHD: 28ug/L (30-100), 1,25OHD:107pg/mL (24-86), PTH:84.5ng/L (15-65), Cre:0.12mg/dL (0-0.42), Mg:2.0mg/dL (1.8-2.6), U-Ca/Cre:0.22mg/mg (0.03-0.8), U-PO4/Cre:0.94mg/mg (<5.2), TRP:94% (85-100), TmP/GFR:2.31 (4.8-8).
Serial skeletal X-rays revealed diffuse osteosclerosis at birth which was gradually resolved by the age of 5 months and medullary space of long bone could be distinguishable with bone-in-bone appearance. At 9 month of age hand X-ray revealed cupping of ulna with loose radial bone margin with minimal fraying and osteopenia. Cranial CT scan showed bilateral periventricular calcification with cerebral atrophy. The clinical, laboratory and radiological examinations were consistent with RS. Molecular analyses revealed a compound heterozygous mutation in FAM20Cgene (a known pathogenic mutation,c.1645C>T, p.Arg549Trp,; and a novel insertion, c.953_956insACAGGTGAGCCC)
Conclusion: We described a novel variant in FAM20Cgene contributing to RS phenotype. Although rare, RS should be considered in differential diagnosis of FGF23 related hypophosphatemia in patients with typical craniofacial abnormalities.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology