Nevoid Basal Cell Carcinoma Syndrome is a complex inherited condition that affects various body systems. It is characterized by a predisposition to developing both cancerous and non-cancerous tumors, with basal cell carcinomas being a prominent feature. This disorder is syndromic, meaning it involves a collection of signs and symptoms that occur together, rather than being limited to a single medical issue. It is a rare disorder.
Understanding Nevoid Basal Cell Carcinoma Syndrome
Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is also known as Gorlin syndrome or Gorlin-Goltz syndrome. This condition stems from a genetic alteration, primarily caused by mutations in the PTCH1 gene. The PTCH1 gene functions as a tumor suppressor, which helps regulate cell growth and division, preventing uncontrolled proliferation.
When a mutation occurs in PTCH1, or less commonly in SUFU or PTCH2 genes, this regulatory function is impaired. This leads to rapid cell growth and division, contributing to tumor formation and various developmental issues. The inheritance pattern for NBCCS is autosomal dominant, meaning only one altered copy of the gene is sufficient for the condition to manifest. There is a 50% chance an affected parent will pass the mutated gene to each offspring.
While the condition is inherited, its presentation can vary significantly, even among family members who share the same genetic mutation. Some individuals may experience only a few symptoms, while others develop a broader range of features. This variability highlights the complex nature of genetic expression.
Recognizing the Signs and Symptoms
Basal cell carcinomas (BCCs) are a hallmark feature and the most common skin cancer in this syndrome. These skin cancers often appear during adolescence or early adulthood, frequently on sun-exposed areas like the face, chest, and back, but can also occur on covered skin. They can vary in appearance, resembling flesh-colored or pink bumps, and individuals may develop multiple lesions, from a few to thousands, over their lifetime.
Odontogenic keratocysts are non-cancerous cysts that develop within the jawbones, often appearing in multiples and commonly diagnosed in children and young adults with NBCCS. These cysts can lead to swelling, pain, or displacement of teeth if left untreated. Skeletal abnormalities are also common and can include bifid or fused ribs, vertebral anomalies like scoliosis, and distinctive facial features such as a prominent forehead or widely spaced eyes.
Small depressions on the palms of the hands and soles of the feet, known as palmar and plantar pits, are another characteristic sign common in affected individuals. Typically 1-3 mm, they can become more noticeable after soaking hands or feet in warm water. Neurological manifestations include an increased risk of specific brain tumors, such as medulloblastoma, particularly in childhood. Less common features include benign heart tumors (cardiac fibromas) or ovarian fibromas in females, and certain eye abnormalities.
How Nevoid Basal Cell Carcinoma Syndrome is Diagnosed
Diagnosing Nevoid Basal Cell Carcinoma Syndrome typically involves a thorough clinical evaluation, looking for characteristic physical signs. A physical examination by a dermatologist or geneticist identifies features like multiple basal cell carcinomas or palmar pits.
Imaging studies are significant for diagnosis. X-rays are often used to check for jaw cysts and skeletal anomalies, including rib and spinal abnormalities. Magnetic Resonance Imaging (MRI) may be used to screen for brain tumors or other neurological issues, especially in younger individuals.
Genetic testing, to identify PTCH1 gene mutations, serves as a confirmatory diagnostic tool. It is valuable when clinical features are subtle or to confirm a diagnosis. Given the syndrome’s varied manifestations, a multidisciplinary approach involving specialists like dermatologists, geneticists, oral surgeons, and oncologists is often necessary for a comprehensive diagnosis.
Living With and Managing the Syndrome
Living with Nevoid Basal Cell Carcinoma Syndrome involves ongoing management and regular surveillance to monitor and address potential complications. Lifelong monitoring includes frequent skin examinations to detect new basal cell carcinomas early. Periodic dental imaging is crucial for identifying and tracking jaw cysts. Neurological screening, such as MRI in childhood, is recommended due to the risk of medulloblastoma.
Treatment for basal cell carcinomas in individuals with NBCCS can involve surgical removal, a common approach. Other options like topical therapies or oral medications that target specific cellular pathways, such as the Hedgehog pathway, may be considered, especially for numerous lesions or those in sensitive areas. Radiation therapy for BCCs is generally avoided in NBCCS patients due to an increased risk of new cancer in irradiated areas.
Management of other manifestations includes surgical removal of jaw cysts to alleviate pain and prevent complications. Skeletal abnormalities may require orthopedic intervention if they cause significant issues. Genetic counseling is a crucial component of care, providing affected individuals and families with information about inheritance patterns and reproductive options. Support groups and specialized centers offer comprehensive care and resources for individuals navigating this condition.