Bone Abstracts (2015) 4 P197 | DOI: 10.1530/boneabs.4.P197

Benign osteopetrosis associated with homozygous mutation in CLCN7

Jeremy Allgrove1, Satheesh Mathew1, Chris C Buxton2 & Maggie Williams2

1Barts Health NHS Trust, London, UK; 2Bristol Genetics Laboratory, Bristol, UK.

Introduction: Benign osteopetrosis type 2 (OPTA2) (Albers-Schönberg disease) is usually associated with a heterozygous mutation in CLCN7. Patients may be asymptomatic and present following an x-ray taken for other reasons or with a low trauma fracture. There may be a family history. Homozygous mutations in CLCN7 usually result in severe disease which presents in the neonatal period or early infancy. We present a case of benign osteopetrosis associated with a homozygous variant in CLCN7 that was diagnosed incidentally.

Presenting problem: A 6 year-old girl was referred to the metabolic bone clinic for an opinion on increased bone density. She had been noted to have a heart murmur for which she had had a chest x-ray. This had shown generalised increase in bone density. Further investigation of the heart murmur showed this to be caused by a small ASD which was asymptomatic. She had no history of fractures and was otherwise quite well. Both parents are well as are her two sisters. The parents are consanguineous.

Clinical management: Further investigations revealed a very high bone density (BMD z-score+6.1) but routine biochemistry was all normal. Genetic analysis of genes for osteopetrosis showed a homozygous variant in CLCN7. LRP5 mutation analysis was negative. DXA scans of her two sisters showed that her older sister has a normal BMD but her younger sister’s BMD is +2.3. Father’s BMD was also normal. Mother has not had a DXA as she is pregnant. Genetic analysis of the other family members is awaited. Because of the lack of symptoms, she has not had any specific treatment.

Discussion: Homozygous mutations in CLCN7 usually give rise to osteopetrosis with severe disease whilst heterozygous mutations cause mild, often asymptomatic disease. This case is unusual in that she has a genotype suggestive of severe disease with a mild phenotype. It is currently not clear if the variant is contributing to her clinical phenotype and further family studies are ongoing to try to establish this.

Disclosure: The authors declared no competing interests.

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