osteoporosis, childhood- or juvenile-onset, with developmental delay

Osteoporosis, childhood- or juvenile-onset, with developmental delay is a condition that affects both skeletal development and the central nervous system. It is characterized by reduced bone density along with developmental challenges that become apparent early in life. The underlying genetic basis is linked to variants in the COPB2 gene, and the condition is inherited in an autosomal dominant pattern. Precise prevalence estimates are not available, with current knowledge primarily based on clinical observations of affected individuals.

Individuals with this condition consistently show global developmental delay and osteopenia, which are the hallmark features observed in every case. Many affected children also exhibit central nervous system involvement, including intellectual disability, delayed CNS myelination, and seizures. Additional findings can include a thin corpus callosum, microcephaly, a broad-based gait, and difficulties with walking, along with features such as spasticity and recurrent fractures. Not all individuals experience all features, and severity varies considerably.

This condition is linked to pathogenic variants in the COPB2 gene, which is believed to play a role in intracellular protein trafficking and bone development. It is inherited in an autosomal dominant manner, meaning that a single copy of the altered gene can lead to the condition. As a result, an affected individual has a 50% chance of passing the variant on to each offspring, although the clinical presentation may differ due to variable expressivity. Genetic counseling is recommended to help families understand these implications.

Currently, management focuses on supportive care and symptom management, as there are no treatments specifically approved for this condition. A multidisciplinary approach is often used, involving physical therapy, occupational therapy, and other supportive interventions to address both skeletal and neurodevelopmental challenges. Patients should discuss treatment options with their healthcare team to determine which therapies may be most beneficial for their individual situation, and genetic counseling is also recommended for family planning.

Outcomes vary widely among affected individuals, with the clinical course influenced by the severity of both skeletal and developmental features. With current standards of care, many individuals can live into adolescence and adulthood, although challenges with mobility and cognitive function may persist. The overall course is highly variable, and outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with the condition, and genetic counseling can provide guidance regarding future family planning.