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Bone Abstracts (2017) 6 P115 | DOI: 10.1530/boneabs.6.P115

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Expanding the genotype--phenotype correlation of osteogenesis imperfecta with a novel mutation in Col1A2 gene

Maimoona Al Qanoobi, Harriet Ryan & Ciara McDonnell

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Children’s University Hospital, Temple St., Dublin, Ireland.


Background: Osteogenesis imperfecta [OI] is a disorder of bone fragility with a variable spectrum of severity and poor correlation of antenatal findings with postnatal outcome. We present two antenatal diagnosed cases with a mild postnatal course significant for the absence of fractures and progressive remodelling of the long bones. A novel heterozygous pathogenic mutation predicted to replace glycine with aspartic acid at position 913 in exon 42 of the COL1A2 gene has been identified in both cases.

Presenting problem: Case 1: A female proband born at term by C-section was identified on scan at 20-weeks’ gestation to have bowed femori. Postnatally, she had marked curvature of her lower limbs, left talipes, frontal bossing, flat feet, hypermobile joints and white sclerae. Her height is <0.4th percentile. Her head circumference was persistently > 99th centile. Routine CT identified mild dilatation of the lateral ventricles and evidence of basilar invagination. She has no neurological symptoms. Case 2: A male proband born at 36-weeks’ gestation by normal vaginal delivery was identified on antenatal scan to have short long bones and angulation of his femori. Postnatally he had curved lower limbs, a right parietal skull fracture, frontal bossing, flat feet and white sclerae. His height is 9–25th centile.

Clinical management: Both children [female now 6yo, male 2.4 years] attend endocrine clinic for regular monitoring for complications of osteogenesis imperfecta. In both cases, motor development, dentition and hearing are normal and neither has had further fracture. Both have normal height velocity with mid-parental height on the 2nd centile. Neither is indicated for bisphosphonate therapy. Both children are monitored for symptoms of basilar invagination. Both attend local intervention services for allied health resources. In both cases the lower limbs have demonstrated progressive remodelling without intervention. Both children have healthy unaffected siblings but the mother of the male proband mother shares the clinical phenotype.

Discussion: Published genotype-phenotype correlations suggest that C-terminal mutations involving glycine substitution with aspartic acid would be suggestive of a higher risk of lethality or a more severe outcome. Phenotyping of antenatal cases based on early ultrasound findings and genotype remain fraught with uncertainty and can result in milder outcomes.

Disclosure: The authors declared no competing interests.

Volume 6

8th International Conference on Children's Bone Health

ICCBH 

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