Case Report

Three Patient Kindred with a Novel Phenotype of Osteogenesis Imperfecta due to a COL1A1 Variant


  • Nidhi Gupta
  • Seth W. Gregory
  • David R. Deyle
  • Peter J. Tebben

J Clin Res Pediatr Endocrinol 0;0(0):0-0 [e-Pub] PMID: 32519829

Osteogenesis Imperfecta (OI) is characterized by fractures and progressive bone deformities. Fracture rates peak during the toddler and adolescent years and decline during adulthood but do not stop entirely. We describe a 3-person kindred (mother and 2 sons) who presented with a unique phenotype of OI. Our patients demonstrated a pattern of prenatal bone deformities followed by multiple nontraumatic long bone fractures within the first two years of life and then an absence of nontraumatic fractures thereafter. No extraskeletal manifestations have been noted to date. The mother did not receive bisphosphonate therapy but had no nontraumatic fractures after age 5 months. Intravenous bisphosphonate therapy was started for both sons within 2 months of birth with the most recent infusions at age 18 months and 28 months in patient 2 and 3 respectively. Two patients harbored a variant of uncertain significance in the COL1A1 gene. This heterozygous variant, c.3548C>T; p.(Pro1183Leu), is listed in the OI Variant Database as affecting only 1 other individual with osteopenia. We describe 3 family members with a unique presenting phenotype of OI, characterized by cessation of nontraumatic fractures after the first two years of life.

Keywords: fragility fractures, collagen, child, bisphosphonates, bone density