A Non-Lethal Osteogenesis Imperfecta Type II Mutation

Abstract

Background: We discuss the ethical decision points in a case report that describes a novel COL1A1 mutation associated to Osteogenesis Imperfecta type II, but with a non-lethal outcome.

Case: A 33-year-old female underwent a 21-week ultrasound that revealed short bowed femurs and humeri with old fractures and bowed tibias and fibulas. Amniotic fluid testing revealed a novel COL1A1 mutation (c.1840G>A; p.Gly614Arg). OI Type II diagnosis was made. A previously reported mutation of the same gene but different locus (c.1840G>C; p.Gly614Arg) led to a lethal form of OI type II. The newborn was delivered via a cesarean delivery and intravenous bisphosphonates (Zaledronic acid) was administered every 3 months. Currently the infant is 22 months old, is growing, with mild bilateral conductive hearing loss.

Conclusion: The unexpected clinical outcome should serve as a reminder that phenotypic variability can occur with genetic mutations. Our case shows that the diagnosis of the type of OI should be based not only on clinical findings and genetic investigations but also on the clinical course over time.

Keywords: Amniocentesis; Bisphosphonate; COL1A1 mutation; Collagen; Fetal fractures; Skeletal dysplasia; Ultrasound.