autosomal dominant osteopetrosis 1

Autosomal dominant osteopetrosis 1 is a sclerosing bone disorder that primarily affects the cranial vault, leading to increased bone density. This condition is caused by variants in the LRP5 gene and follows an autosomal dominant inheritance pattern, meaning a single altered copy of the gene can be sufficient to cause the disease. It is very rare, affecting fewer than 1 in 1 million people. Although symptoms may become apparent at different ages, the clinical presentation is highly variable between individuals.

Individuals with autosomal dominant osteopetrosis 1 may present with a range of skeletal findings. A majority have evidence of calvarial osteosclerosis as well as a thickened cortex of the long bones, observed in approximately 30 to 79% of affected persons. Other reported features include the development of a bony growth on the palate known as torus palatinus, while a smaller proportion may experience symptoms such as mandibular pain and headaches. That not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the LRP5 gene, which plays a key role in bone metabolism and remodeling. Autosomal dominant inheritance means that an affected individual has a 50% chance of passing the variant on to each child. Moreover, the clinical presentation can vary among affected family members, with some individuals experiencing significant skeletal manifestations while others may have milder symptoms. Genetic counseling is recommended for families to understand the implications of inheritance and to discuss potential risks for future pregnancies.

Currently, management focuses on supportive care and symptom management because there are no FDA-approved treatments specifically for this condition. Treatment is tailored to the individual, often involving a multidisciplinary team to address pain, structural complications, and other related issues. Patients are encouraged to discuss treatment options with their healthcare team, and genetic counseling is recommended to assist families in understanding management strategies, including approaches to monitor and address skeletal complications as they arise.

Outcomes for individuals with autosomal dominant osteopetrosis 1 are highly variable and depend on the range and severity of skeletal findings. With current standards of care, many individuals manage their symptoms well into adulthood, although some may experience complications that require ongoing monitoring and intervention. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialized healthcare professionals, and genetic counseling can provide guidance regarding inheritance patterns and long-term management options.