Bone Abstracts

Background: OI-V is an autosomal dominant type of OI, which is characterized by recurrent fractures, hyperplastic callus formation and forearm interosseous membrane calcification. Less than 5% of OI patients are diagnosed with OI-V. The 5’-UTR IFITM5 mutation is a single recurrent heterozygous mutation reported in the majority of these patients.

Presenting problem: The 2 years old girl was born at term, BW 2880g(P25-50), L 48 cm (P25-50), OFC 33 cm(P3). Motor development was delayed, sitting age 15 months, standing without support at 2 years, whereas cognitive development seemed to be normal. At the age of 7 months the girl complained with pain after bending sitting at the mothers womb. X-ray revealed a fracture of the right femur. Spinal X-ray after acute back pain revealed vertebral fractures. A second low impact femur fracture occured at 13 months, suggesting a clinical diagnosis of Osteogenesis imperfecta (OI) type 1. However, molecular analysis of the type I collagen genes (COL1A1 and COL1A2) was normal. There was no history of fractures in the family.

Clinical Management: Fracture healing was noticed to be abnormal with delayed and hypertrophic callus formation. The child was treated with Neridronate 2 mg/kg every 3 months with good response. In follow up care a limitation in forearm supination/pronation was noticed at 1½ years. Molecular analysis of the IFITM5 gene in the proband revealed the presence of the recurrent heterozygous mutation (c.-14C>T) in the 5’ untranslated region (exon 1). Segregation analysis showed that the IFITM5 mutation was absent in the mother but was present in the father, albeit at a lower amount. Subsequent deep sequencing by NGS confirmed the mosaic state of the mutation in the father, revealing a mutation load of 34% in the paternal blood. Bone density in the father was normal.

Discussion: OI-V caused by the 5’-UTR IFITM5 mutation was confirmed in our patient. There are few reports of families with autosomal dominant inheritance from an affected parent. To our best knowledge a transmission from an unaffected parent was not reported before. In view of the implication of families and recurrence risk genetic investigation of healthy parents is warranted.

Disclosure: The authors declared no competing interests.