Buschke–Ollendorff syndrome

Overview

Buschke–Ollendorff syndrome (BOS) is a rare genetic disorder characterized by the presence of skin lesions called connective tissue nevi and bony growth abnormalities known as osteopoikilosis. The condition typically becomes noticeable in childhood or adolescence and is generally benign. While the skin and bones are primarily affected, BOS is important to recognize due to its association with a more severe variant involving cardiovascular complications called LEMD3-related osteopoikilosis. Most individuals with BOS live normal, healthy lives without significant disability.

Causes

Buschke–Ollendorff syndrome is caused by mutations in the LEMD3 gene (also known as MAN1), which plays a role in regulating signaling pathways involved in bone and connective tissue development. The condition is inherited in an autosomal dominant pattern, meaning only one copy of the altered gene is sufficient to cause the disorder. In some cases, the mutation may occur spontaneously without a family history (de novo mutation).

Symptoms

The symptoms of BOS vary in severity, but most individuals exhibit the following features:

• Connective tissue nevi: Small, firm, painless skin-colored papules or plaques, often located on the trunk and upper limbs. These lesions are typically elastin-rich and may be present from childhood.

• Osteopoikilosis: Multiple, small, round or oval areas of increased bone density (bone islands) seen on X-rays. These are usually asymptomatic and discovered incidentally.

• Joint stiffness or mild pain: Occasionally present, though rare and not severe

Most individuals with BOS do not experience functional limitations, and symptoms typically do not worsen with age.

Diagnosis

Diagnosis of Buschke–Ollendorff syndrome is based on clinical findings, imaging, and genetic testing. Key diagnostic steps include:

• Skin examination: Identification of characteristic connective tissue nevi

• X-ray imaging: Detection of osteopoikilosis, often appearing as sclerotic bone lesions near joints

• Histopathology: Skin biopsy showing increased elastic fibers in the dermis

• Genetic testing: Confirmation of mutations in the LEMD3 gene

• Family history evaluation: As the condition is inherited, examination of relatives may help support the diagnosis

Treatment

There is no cure for Buschke–Ollendorff syndrome, but treatment is rarely necessary as the condition is usually benign. Management strategies may include:

• Observation: Most individuals require no treatment due to minimal symptoms

• Symptom relief: Over-the-counter pain relievers for occasional joint discomfort

• Cosmetic consultation: If skin lesions are bothersome for aesthetic reasons, dermatologic treatments such as laser therapy may be considered

• Genetic counseling: Recommended for affected individuals and their families to understand inheritance and recurrence risk

Prognosis

The prognosis for individuals with Buschke–Ollendorff syndrome is excellent. The condition does not affect life expectancy or overall health in the vast majority of cases. Skin lesions are benign and usually do not cause discomfort, while bone findings are non-progressive and typically asymptomatic. Regular follow-up may be advised if there are any unusual symptoms or if there is suspicion of a more severe variant. With appropriate diagnosis and awareness, individuals with BOS can lead completely normal lives.