Spondyloenchondrodysplasia with immune dysregulation

Spondyloenchondrodysplasia with immune dysregulation is a very rare multisystem condition that primarily affects bone development and the immune system. It is caused by pathogenic variants in the ACP5 gene, which plays an important role in bone remodeling and immune function. Affected individuals typically present in childhood with distinctive skeletal changes such as metaphyseal widening and short stature along with immunological abnormalities. This condition is extremely rare, affecting fewer than 1 in 1,000,000 people.

The clinical presentation involves a broad spectrum of features affecting multiple organ systems. Nearly all affected individuals have skeletal abnormalities, including metaphyseal widening, metaphyseal dysplasia, and short stature, with features like platyspondyly and lumbar hyperlordosis also commonly observed. Immune system disturbances such as antinuclear antibody positivity and autoimmune thrombocytopenia may be present, and some individuals experience recurrent respiratory infections. In addition, mild intellectual disability and global developmental delay highlight central nervous system involvement. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by mutations in the ACP5 gene, which is essential for normal bone development and proper immune function. It is inherited in an autosomal recessive manner, meaning that an affected individual has received two mutated copies of the gene, one from each parent. The condition is more common when parents share a common ancestor, as this increases the likelihood that both carry the same rare variant. Genetic counseling is recommended to help families understand the inheritance pattern and implications for future family planning.

Currently, management focuses on supportive care and symptom control as there are no treatments specifically approved for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team addressing skeletal, immunologic, and neurodevelopmental challenges. Regular surveillance is an essential component of long-term care, helping to identify potential complications early. Patients and families are encouraged to discuss treatment options with their healthcare team and to seek genetic counseling for further guidance.

Outcomes for individuals with this condition vary widely, with the clinical spectrum ranging from milder presentations to more complex multisystem involvement. With current standards of care and advances in multidisciplinary management, many individuals are able to achieve a better quality of life as treatment strategies continue to evolve. The condition may progress, stabilize, or show a variable course over time. Families often find it helpful to connect with specialists and genetic counselors to better understand the long-term outlook and plan for future care.