Endocrine Abstracts (2017) 51 P008 | DOI: 10.1530/endoabs.51.P008

Antenatal diagnosis in osteogenesis imperfecta needs more than a gennotype

Fawaz Arshad1,2 & Nicholas Bishop1,2


1Sheffield Children’s NHS Foundation Trust, Sheffield, UK; 2Academic Unit of Child Health, University of Sheffield, Sheffield, UK.


Osteogenesis imperfecta (OI) is a disorder that affects bone material properties, mass and architecture, with resultant bone fragility. Most (85–90%) affected individuals have a mutation in one of the two genes encoding type I collagen (COL1A1/2), although mutations in 16 other genes have been identified that result in congenital bone fragility. Mother A presented in her sixth pregnancy, after having four previous first trimester miscarriages and one well infant. Early antenatal scans showed bowed lower limb bones and poor growth. Amniotic fluid cells showed a COL1A1 defect, reported by the NE Thames Regional Genetics Laboratory as consistent with severe or lethal OI. The baby was deemed to be too severely affected to be entered into an impending fetal mesenchymal stem cell transplant study (BOOSTB4). Parents were offered, and refused, termination. At 34 weeks the ultrasound showed a very small fetus with mild bowing of the lower limbs. Because of the risk attributable to severe growth retardation, the decision to deliver electively at 37 weeks was made. Baby A was born in good condition weighing 1.23 kg and requiring no resuscitation. Expressed breast milk (EBM) feeds started straight away. Newborn and infant physical exam showed diastasis of the skull sutures, bowed lower limb but not upper limb segments, and bilaterally undescended testes. Baby A plotted below 0.4th centile in weight and head circumference. Multidisciplinary team approach was taken, including physiotherapists, speech and language, dietician, neonatologists, metabolic bone team and nurses. Minimal handling was employed with regular turns, particularly head turns, to prevent skull abnormalities. Radiographs confirmed the bowed tibia and femora, with good overall shape, and gracile ribs. The baby is growing very slowly, tracking away from 0.4th centile and has had one bronchiolitis episode at day 40. This case highlights important issues in the approach to genetic diagnosis and antenatal interventions. Specifically, genetic testing does not give the full picture in OI and experience is required to provide an accurate interpretation. In addition, clear definition of the pre-treatment state of the fetus is needed to provide assurance regarding the effect of any antenatal intervention.

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