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

Özet

Osteogenesis imperfecta (OI) is characterized by fractures and progressive bone deformities. Fracture rates peak during the toddler andadolescent years and decline during adulthood but do not stop entirely. We describe a kindred, the affected members of which were themother and two sons, who presented with an apparently unique phenotype of OI. Our patients demonstrated a pattern of prenatal bonedeformities followed by multiple, nontraumatic long bone fractures within the first two years of life and then an absence of nontraumaticfractures thereafter. No extra-skeletal manifestations have been noted to date. The mother did not receive bisphosphonate therapy buthad no nontraumatic fractures after the age of five months. Intravenous bisphosphonate therapy was started for both sons within twomonths of birth, with the most recent infusions at age 18 months and 28 months in Patients 2 and 3, respectively. Two patients harboreda variant of uncertain significance in the COL1A1 gene. This heterozygous variant, c.3548C>T; p.(Pro1183Leu), is listed in the OI VariantDatabase as affecting only one other individual with osteopenia. We describe three family members with a unique presenting phenotypeof OI, characterized by cessation of nontraumatic fractures after the first two years of life.