autosomal recessive osteopetrosis 7

Autosomal recessive osteopetrosis 7 is a very rare inherited bone disorder in which the bones become overly dense and brittle, leading to a range of health problems. The condition is caused by changes in the TNFRSF11A gene, which plays a key role in the development and activity of osteoclasts, the cells responsible for breaking down old bone. Because osteoclast function is impaired, new bone is laid down without the usual remodeling, resulting in abnormally hard but fragile bones. Symptoms usually begin in infancy or early childhood and can affect several body systems. Fewer than one in a million people are thought to have this condition worldwide.

The hallmark features are markedly dense bones (osteopetrosis) and progressive visual loss, which are reported in every individual described. Early signs often include delayed growth, an unusually large head, and fractures that occur with minimal trauma. As the disease evolves, children may develop enlargement of the liver and spleen, low levels of immunoglobulins that increase the risk of infections, and neurological concerns such as nystagmus or low muscle tone. Less common findings include hydrocephalus, seizures related to low calcium levels, and protruding eyes due to changes in the skull bones. Not all individuals experience all features, and severity varies considerably.

Autosomal recessive osteopetrosis 7 results from pathogenic variants in the TNFRSF11A gene. The TNFRSF11A protein is part of a signaling pathway that triggers the formation and activation of osteoclasts. When the gene is not working correctly, osteoclasts are scarce or ineffective, so bone that is formed cannot be broken down and remodeled. The condition follows an autosomal recessive inheritance pattern, meaning a child must receive a non-working copy of TNFRSF11A from each parent to be affected. Parents who each carry one altered copy are usually healthy carriers but have a 25 percent chance with each pregnancy of having an affected child. Because the disorder is very rare, it is more likely to appear in families in which parents share a common ancestor, as this increases the chance that both carry the same rare variant. Genetic counseling can help families understand carrier testing options and implications for future pregnancies.

Currently, management focuses on supportive care and symptom management. Care typically involves a multidisciplinary team that may include orthopedic surgeons for fracture care, ophthalmologists to monitor vision, endocrinologists for calcium balance, immunologists for low antibody levels, and physical therapists to support mobility. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Depending on individual needs, interventions can include protective measures to reduce fracture risk, immunoglobulin replacement to prevent infections, nutritional support to address growth concerns, and close monitoring of head growth and neurological status. Patients should discuss treatment options and appropriate monitoring schedules with their healthcare team to determine the best plan for their situation.

Outcomes vary depending on the severity of bone changes, the degree of vision impairment, and the presence of complications such as fractures or recurrent infections. Some children experience significant physical challenges, while others have milder courses and maintain reasonable mobility with early intervention and careful monitoring. Advances in supportive care, fracture management, and immunologic therapies are helping many affected individuals achieve better quality of life. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition and to engage with genetic counseling for guidance and support.