Buschke–Ollendorff syndrome

Buschke–Ollendorff syndrome is a rare genetic condition that affects the skin and bones. It is caused by mutations in the LEMD3 gene and is passed down in an autosomal dominant pattern. The disorder typically shows up as widespread, painless skin bumps (papules). It occurs in about 1 in every 20,000 people, with equal frequency in males and females. The condition was first described in 1928 by Abraham Buschke and Helene Ollendorff Curth, based on a single female patient.

Signs and symptoms can include osteopoikilosis (dense bone spots), bone pain, connective tissue nevi (skin growths), and abnormalities in the metaphysis (the growing end of bones). Possible complications include aortic stenosis and hearing loss.

The underlying cause is a mutation in the LEMD3 gene, which provides instructions for making a protein called MAN1. This protein sits in the inner nuclear membrane and helps regulate two key signaling pathways: transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP). Both pathways control the growth of new bone cells by directing SMAD proteins to bind to DNA. When LEMD3 is mutated, less MAN1 protein is produced, leading to overactivity of these pathways.

Diagnosis can be made through genetic testing, X-rays, ultrasound, or histological examination of tissue. Conditions that may look similar include melorheostosis and sclerotic bone metastases. Other disorders to consider are tuberous sclerosis, pseudoxanthoma elasticum, neurofibroma, and lipoma.

Treatment focuses on complications. If aortic stenosis develops, surgery may be needed. Hearing loss may also require surgical intervention.