Osteopetrosis is a general name for a group of rare genetic diseases which are all characterised by increased bone density. These result from problems in the formation or function of osteoclasts, cells which dissolve bone so that it can be reshaped during growth or repaired after injury. The dense bones are prone to fracturing easily. Nerves which pass through channels in bone (such as the nerves that pass through the skull to the eye or ear) can be damaged, since these channels do not enlarge as the nerves grow; this can affect vision or hearing.


Medical text written February 2017 by Professor Colin Steward, Consultant in BMT for Metabolic and Genetic Diseases, Royal Hospital for Children, Bristol, UK and Medical Adviser to the Osteopetrosis Support Trust.

Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information is provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

What are the symptoms?

Infantile (‘malignant’) osteopetrosis is the most severe form of the disease. Affected children tend to be short but with relatively large heads. They often sustain birth fractures and may be jittery or have convulsions during the first month of life due to hypocalcaemia (low blood calcium). Subsequently, they develop persistent snuffles (due to narrow nasal passages) and are prone to suffer increased ear, nose and throat, and respiratory infections. Bone marrow cavities are reduced: blood then accumulates in the liver and spleen, causing swelling of these organs and a low blood count may result. Many children become blind (see entry Vision disorders in Childhood) by six months of age, deaf (see entry Deafness) and later may develop hydrocephalus. Tooth eruption may be delayed and tooth quality tends to be poor.

Adult (‘benign’) osteopetrosis is most commonly diagnosed in late adolescence or early adulthood when bones are X-rayed due to a fracture, although it can sometimes be diagnosed in younger children especially where it is an incidental finding on an X-ray. Some people may go on to develop bone pain, dental problems and deafness or facial nerve paralysis. There is currently no specific treatment.

What are the causes?

It is now known that mutation in one of more than 10 different genes is responsible for three quarters of cases; the cause remains unknown in the remainder. These genes include those which code for a proton pump (TCIRG1, in 50% of those affected), chloride channel (ClCN7), carbonic anhydrase (CAII), OSTM1, RANK (TNFRSF11A), RANK Ligand (TNFSF11), cathepsin K (CTSK), PLEKHM1, SNX10 and NF-kB Essential Modulator (NEMO).

How is it treated?

Without treatment many affected children die before adolescence. However, at least half of children affected by the disease can be helped by haemopoietic stem cell transplantation (HSCT) using bone marrow, cord blood or peripheral blood stem cells from family or unrelated donors. Stem cells from the blood or bone marrow can give rise to a variety of specialised cells including osteoclasts, allowing replacement of the absent or ineffective osteoclasts that cause the increased bone density. HSCT is very effective for many types of infantile osteopetrosis including the commonest type due to TCIRG1 mutations. Severe brain problems can develop some time after otherwise successful transplants in children with ClCN7 mutations and always develop in those with OSTM1 mutations. Transplantation therefore has an unclear role in ClCN7 disease and must not be performed in OSTM1 disease. It also does not work for children whose disease is caused by TNFSF11 mutations and has not been reported in autosomal dominant osteopetrosis (ADO) disease. Expert assessment and genetic analysis is therefore important if inappropriate transplantation is to be avoided.

Injections of gamma interferon may be effective in alleviating some symptoms of the disease, but are not widely used.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Autosomal recessive disease may result from mutation of any of 10 or more genes identified as causing osteopetrosis. A total of 50 per cent of babies/infants with osteopetrosis will have mutations of TCIRG1 and 15 per cent will have mutations of ClCN7.

Adult osteopetrosis is usually due to dominant mutations of ClCN7, and is therefore termed autosomal dominant osteopetrosis (ADO).

Prenatal diagnosis
Accurate prenatal diagnosis is possible in families with known gene mutations by either chorionic villus sampling or amniocentesis from ten weeks of pregnancy onwards. For other families prenatal diagnosis is less reliable and depends on detection of changes in the fetus by X-ray or ultrasound in the last third of pregnancy; both tests may still fail to detect accurately affected fetuses.

Is there support?

Osteopetrosis Support Trust

Email: info@osteopetrosis-support-trust.org.uk
Website: osteopetrosis-support-trust.org.uk

The Osteopetrosis Support Trust is a parent run support group for families with children affected by Osteopetrosis. They provide information and support, aim to raise awareness of the condition and promote scientific research.

Group details updated January 2018.

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