Bone Abstracts

Background: Osteogenesis imperfecta (OI) is a genetic disorder with low bone mass and bone fragility. Type VII OI is one of the autosomal recessive subtypes and clinically moderate to lethal. It is caused by mutations in the cartilage associated protein (CRTAP) gene. Currently <20 mutations are known.

Case description: An 11-year-old Iraqi female was referred to our hospital after immigration to Finland. She had suffered numerous peripheral and spinal fractures. At presentation she had severe vertebral and limb deformities and could not stand, her height was 75 cm. The lumbar spine and whole body BMD Z-scores were −5.6 and −3.0, respectively. The clinical and radiographic features were consistent with OI. Her parents and three siblings were healthy; one sibling had died soon after birth due to similar bone disease. The parents were 1st cousins.

All known OI genes were analysed with flanking markers. The genes flanked by homozygous markers were chosen for direct sequencing. A homozygous mutation (c.141dupC) was identified in exon 1 of the CRTAP gene. The mutation leads to a premature stop codon. Both parents were heterozygous carriers of the mutation. The mutation has not previously been described.

The patient has received intravenous pamidronate and zoledronic acid treatment for 3 years. Spinal deformity required surgery. Bisphosphonate treatment improved subjective well-being and reduced bone pain and she is able to sit for much longer periods.

Discussion: This family illustrates the extreme severity of type VII OI. Bisphosphonate treatment was of subjective benefit even though it was not started until age 11. The reported novel CRTAP mutation expands the genetic defects associated with OI type VII.