ESPN 51th Annual Meeting

ESPN 2018


 
A CASE REPORT OF NON LETAL RAINE SYNDROME
SVETLANA PAPIZH 1

1- RESEARCH AND CLINICAL INSTITUTE OF PEDIATRICS, RUSSIAN NATIONAL RESEARCH MEDICAL UNIVERSITY
 
Introduction:

Raine syndrome (RNS) (OMIM #259775) is a rare inherited disorder characterized by osteosclerotic bone dysplasia, dysmorphic facies, ectopic soft tissue mineralization, dental abnormalities due to gene FAM20C mutations, which encodes dentin matrix protein 4. RNS was originally reported as a lethal syndrome in infancy, but some cases have been described as survival into childhood and adulthood.

Material and methods:

We report a patient with Raine syndrome.

Results:

A girl, the third child of unrelated parents with negative  family history of bone and kidney disease.  Birth weight was 3450 g, height 52 cm, Apgar scores were 8/9. She had perinatal respiratory problems due to choanal hypoplasia. Computerized tomography (CT)  scan revealed intracranial calcifications. Mildly dysmorphic facies was observed as she grew. Severe dental demineralization were already reported in the first year of life. Rickets appeared in the second year of life. The girl was examined in  our clinic at first time at the age of 2 years. On admission  she had short stature (height 88 cm (3 pc), weight 13.9 kg (25-50 pc)), mild bilateral exopthalmos, depressed nasal bridge, large frontal encephalocele, low set ears, high arched palate, rickets, nails hypotrophy. On examination she had hypophosphatemia 1.14  mmol/l, increased serum alkaline phosphatase (APL) activity – 1139 U/l; acid base, electrolytes were normal.  Serum levels of metabolites of vitamin D, thyroid and parathyroid hormones were normal. Excretion calcium, phosphorus with urine were normal, decreased  level of maximum reabsorption rate of phosphate (TmP/GFR=0.19).  She had normal renal function,  eGFR 109.6  ml/min/1,73m2.  Renal  US scan, echocardiography were normal.    Long bone x-rays showed widening of the metaphyses and severe osteomalacia. CT findings revealed intracranial calcifications. Genetic analysis was performed by next generation sequencing revealed compound heterozygous mutations c.708C>A in exon 2 and c.1375C>T in exon 8 of FAM20C gene, firstly identified. Sanger sequencing  was revealed mutation c.708C>A in the father, c.1375C>T in the mother.  The girl has been treated with  high doses of  phosphate   (100.0 mg/kg/d) and an active vitamin D metabolite (alphacalcidol) 35 ng/kg/d in the first year and mild doses of phosphate   (40.0 mg/kg/d) in the second and third years. Follow-up after 3 years of this  treatment showed   that physical development become normal (height 1078 cm (3 pc), weight 13.9 kg (25-50 pc), disappearance of rickets. Laboratory findings were constant: serum phosphate  levels  (0.8-0.9  mmol/l) and  TmP/GFR were decreased; APL (960-1200 U/L) were increased.  X-rays showed widening of the metaphyses and mild osteomalacia.

Conclusions:

The clinical phenotype of non-lethal RNS is more variable. Our findings suggest that certain FAM20C mutations can cause hypophosphatemic osteomalacia. Therapy with high doses of vitamin D and phosphate can have a good long-term effect.