Jaffe–Campanacci syndrome

Overview

Jaffe–Campanacci syndrome is a rare genetic disorder characterized by the presence of multiple non-ossifying fibromas in the long bones, jaw, and other skeletal sites, often associated with skin pigmentation abnormalities and other systemic features. It is considered a variant or overlap of neurofibromatosis type 1 (NF1) due to the similarity in clinical features. The syndrome can lead to frequent bone fractures, skeletal deformities, and, in some cases, endocrine or developmental abnormalities.

Causes

The exact cause of Jaffe–Campanacci syndrome is not fully understood, but it is strongly associated with mutations in the NF1 gene, the same gene responsible for neurofibromatosis type 1. This gene provides instructions for making a protein called neurofibromin, which helps regulate cell growth. Mutations in NF1 can result in uncontrolled cell proliferation, leading to tumor development and bone lesions. While many cases are sporadic, the condition may follow an autosomal dominant inheritance pattern in cases linked to NF1 mutations.

Symptoms

Individuals with Jaffe–Campanacci syndrome may present with a combination of skeletal and dermatological features. Common symptoms include:

• Multiple non-ossifying fibromas, especially in the femur, tibia, and jawbones

• Frequent bone fractures and skeletal deformities due to weakened bone structure

• Café-au-lait spots (light brown skin patches)

• Delayed bone healing and limb length discrepancies

• Occasional endocrine abnormalities such as hypogonadism or precocious puberty

• In some cases, intellectual disabilities or learning difficulties

• Absence or minimal presence of typical neurofibromas despite the association with NF1

Diagnosis

Diagnosis of Jaffe–Campanacci syndrome is based on a combination of clinical, radiological, and genetic findings. Key steps in the diagnostic process include:

• Radiographic imaging (X-rays, CT scans, or MRI) showing multiple non-ossifying fibromas

• Skin examination revealing café-au-lait spots and other pigmentary changes

• Assessment of fracture history and skeletal abnormalities

• Genetic testing to detect mutations in the NF1 gene

• Exclusion of other disorders such as fibrous dysplasia or classic NF1 based on the full clinical presentation

Treatment

There is no specific cure for Jaffe–Campanacci syndrome; treatment is directed toward managing symptoms and preventing complications. A multidisciplinary approach is often necessary, involving orthopedists, geneticists, and endocrinologists. Treatment options may include:

• Surgical stabilization or curettage of large bone lesions to prevent or repair fractures

• Physical therapy and rehabilitation to maintain mobility and muscle strength

• Orthopedic braces or corrective surgery for limb deformities

• Monitoring and management of endocrine abnormalities

• Genetic counseling for affected individuals and families

Prognosis

The prognosis for individuals with Jaffe–Campanacci syndrome varies depending on the severity and extent of skeletal involvement. With appropriate orthopedic management and supportive care, most patients can lead functional lives. However, the risk of fractures and bone complications remains high, and close monitoring is essential. Intellectual development is typically normal unless associated with underlying neurofibromatosis-related features. Long-term outcomes are generally favorable with comprehensive care, although some individuals may experience chronic orthopedic issues requiring ongoing intervention.