Endocrine Abstracts

Background: Osteogenesis imperfecta is a systemic connective tissue disorder characterized by low bone mass and bone fragility leading to low-trauma fractures or fractures in atypical locations. Extraskeletal manifestations may include dental anomalies, blue-gray sclera, hearing loss, joint hypermobility, muscle weakness, cardiovascular and pulmonary complications.

Case presentation: A 7year old boy presented with a history of fracture right femur 1 month ago after a trivial trauma. He sustained fracture of right femur 3 times in the past. There was no history of renal calculi. Family history was non-contributory. On examination, he had bowing of legs. His height was 121.5 cm (C0.8 standard deviation), arm span was 126 cm, Upper to lower segment ratio was 0.97. Tanner’s staging was prepubertal. Investigations revealed serum calcium 9.7 mg/dl, phosphorus 4.5 mg/dl, 25(OH)vitamin D3 15.2 ng/ml, Alkaline phosphatase 80 IU/l. Renal, liver, thyroid functions were normal. urine pH 6.5. He underwent open reduction and internal fixation. Vitamin D replacement was initiated as he had vitamin D deficiency. Gene panel testing for osteogenesis imperfecta was done as there was a strong clinical suspicion. A heterozygous missense variant c.2764GOC (p. Gly922Arg) in exon 42 of the COL1A2 gene was detected. Functional studies haven’t been carried out yet due to financial constraints. Patient is being followed up for progress and treated with bisphosphonates to prevent further fractures.

Conclusion: With the advances in next-generation sequencing technology and its wide availability, novel pathogenic variants in established osteogenesis imperfecta genes and new genes are being identified. According to literature review, this mutation is novel and is being reported for the first time. Clinical features are mostly suggestive of osteogenesis imperfecta type 4. In cases of recurrent fracture with strong clinical suspicion, genetic analysis helps in diagnosing osteogenesis EYES 2021 Endocrine Abstracts (2021) Vol 75 imperfecta. Genetic confirmation helps in further management, fracture prevention and counseling the family members.