nevoid basal cell carcinoma syndrome

Nevoid Basal Cell Carcinoma Syndrome (NBCCS): A Rare Genetic Disorder

Nevoid basal cell carcinoma syndrome, also known as Gorlin-Goltz syndrome or Gorlin syndrome, is a rare genetic disorder characterized by a variety of developmental abnormalities and an increased predisposition to cancer, particularly basal cell carcinoma of the skin.

Key Features:

• Basal Cell Carcinoma: The most common type of skin cancer, often appearing on the face, hands, or neck.
• Keratocystic Odontogenic Tumors: Benign cysts in the jawbone that can form from adolescence until about age 30.
• Pits or Small Indentations: On the soles of the feet or palms of the hands.
• Developmental Abnormalities: May include a large head, unusual facial features, small pits on the skin, abnormalities of the spine, ribs, or skull, eye problems, and developmental issues.

Other Possible Signs and Symptoms:

• Benign tumors in the jaw, heart, or ovaries
• Large head and coarse facial features
• Small pits on the hands and feet
• Abnormalities of the spine, ribs, or skull
• Eye problems
• Developmental problems

Inheritance Pattern: NBCCS is inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene is enough to cause the condition. This results in high penetrance and variable expressiveness.

Increased Risk:

• Ovarian tumors
• Skin cancer (basal cell carcinoma)
• Other cancers

References:

• [1] Gorlin syndrome can be caused by mutations at specific areas within an individual’s genetic information, affecting genes such as PTCH1, SMO, and SUFU. ([2])
• NBCCS is characterized mainly by the presence of multiple odontogenic keratocysts (75%), basal cell carcinomas, and other developmental abnormalities. ([6])
• The syndrome has been given several different names, including Nevoid Basal Cell Carcinoma Syndrome, Gorlin-Goltz syndrome, and Basal Cell Nevus Syndrome. ([13])

Common Signs and Symptoms of Nevoid Basal Cell Carcinoma Syndrome

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a rare genetic disorder that can affect multiple organ systems in the body. The signs and symptoms of NBCCS can vary from person to person, but here are some common ones:

• Basal Cell Carcinomas: The most common type of skin cancer, often appearing on the face, hands, or neck.
• Keratocystic Odontogenic Tumors: Benign cysts in the jawbone that can form from adolescence until about age 30.
• Pits or Small Indentations: On the soles of the feet or palms of the hands.
• Skeletal Abnormalities: Such as bifid ribs (ribs split into two pieces) and wedge-shaped vertebrae.
• Unusual Facial Appearance: A large head, coarse facial features, and facial milia (small bumps on the skin).
• Eye Problems: And developmental problems.

Other Possible Symptoms

In addition to these common signs and symptoms, people with NBCCS may also experience:

• Unexplained weight loss
• Loss of appetite
• Aches, pains, lumps
• Abnormal deposits of calcium in the brain
• Bone abnormalities of the spine, ribs, or skull

Important Note

It's essential for individuals with NBCCS to avoid exposure to radiation and to closely monitor their bodies for signs and symptoms that could signal tumors. Early detection and treatment can significantly improve outcomes.

References:

[1] Context 1: Signs of Gorlin syndrome can vary. [2] Context 3: The disorder involves the skin, nervous system, eyes, endocrine glands, urinary and reproductive systems, and bones. [3] Context 4: Patients and parents should be alert to signs and symptoms of NBCCS. [4] Context 5: Symptoms include basal cell cancers, jaw cysts, skin pits on the hands and feet, and abnormal deposits of calcium in the brain. [5] Context 13: Many individuals have a recognizable appearance with macrocephaly, frontal bossing, coarse facial features, and facial milia.

Diagnostic Tests for Nevoid Basal Cell Carcinoma Syndrome (NBCCS)

Nevoid basal cell carcinoma syndrome, also known as Gorlin syndrome, is a rare genetic disorder characterized by the development of multiple basal cell carcinomas and other abnormalities. Diagnostic tests are essential to confirm the diagnosis of NBCCS.

Major Diagnostic Criteria

According to Evans et al. [1], a diagnosis of nevoid basal cell carcinoma syndrome can be made based on the presence of two major and one minor diagnostic criteria or one major and three minor criteria.

• Major criteria:
  • More than five basal cell carcinomas in any individual over their lifetime (Criteria 2)
  • One basal cell carcinoma developing before the age of 20 (Criteria 2)
• Minor criteria:
  • Keratocystic odontogenic tumors (benign cysts in the jawbone) (Criteria 1)
  • Pits or small indentations in the soles of the feet or palms of the hands (Criteria 1)

Diagnostic Tests

The following diagnostic tests can be used to confirm the diagnosis of NBCCS:

• Genetic testing: Molecular genetic testing for PTCH1, SUFU, and other genes associated with NBCCS is essential for establishing a definitive diagnosis [3][4].
• Imaging studies: Imaging studies such as X-rays, CT scans, or MRI can be used to evaluate the extent of basal cell carcinomas and other abnormalities.
• Skin biopsy: A skin biopsy may be performed to confirm the presence of basal cell carcinoma.

Other Diagnostic Tests

Additional diagnostic tests that may be recommended include:

• Echocardiogram (ultrasound of the heart)
• MRI of the brain
• X-rays of the bones, teeth, and other affected areas

It is essential to consult with a healthcare provider or genetics counselor for proper evaluation and diagnosis.

References: [1] Evans et al. (1993) [2] Criteria 2 [3] DG Evans (2024) [4] Genetic testing

Treatment Options for Nevoid Basal Cell Carcinoma Syndrome

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a rare genetic disorder characterized by the development of multiple cutaneous basal cell carcinomas. While there are various treatment options available, drug treatment has emerged as a promising approach.

Topical Treatments

• Imiquimod: A topical cream that has been shown to be effective in treating superficial basal cell carcinomas, with response rates of over 80% [6]. Imiquimod works by stimulating the immune system to attack cancer cells.
• 5-Fluorouracil: A topical chemotherapeutic agent used to treat superficial basal cell carcinoma [8].

Oral Treatments

• Vismodegib: The first systemic treatment approved for metastatic or locally advanced basal cell carcinoma, and a promising option for patients with NBCCS [14]. Vismodegib works by inhibiting the sonic hedgehog pathway, which is involved in the development of basal cell carcinomas.
• LDE225: A sonic hedgehog pathway inhibitor that has been shown to be effective in treating basal cell carcinomas in patients with NBCCS [5].

Newer Medications

• Newer medications are in development for rational drug treatment of patients with SOFU gene variants, which are associated with NBCCS [4]. These medications aim to target specific genetic mutations involved in the disease.

Key Points

• Radiation therapy should be avoided if possible, and digital x-rays should be used when necessary.
• Patients with NBCCS should be screened for hundreds of gene variations that might be important for drug use.
• Topical treatments such as imiquimod and 5-fluorouracil can be effective in treating superficial basal cell carcinomas.
• Oral treatments like vismodegib and LDE225 have shown promise in treating basal cell carcinomas in patients with NBCCS.

References:

[4] - Context result 4 [5] - Context result 5 [6] - Context result 6 [8] - Context result 8 [14] - Context result 14

The differential diagnosis for Nevoid Basal Cell Carcinoma Syndrome (NBCCS), also known as Gorlin syndrome, includes several conditions that can present with similar symptoms.

• Bazex syndrome: This is a rare genetic disorder characterized by the development of basal-cell carcinomas and palmoplantar keratodermas. It is often associated with mutations in the STS gene [3][7].
• Torre's syndrome (Muir-Torre's syndrome): This is a rare autosomal dominant disorder that combines multiple basal cell carcinomas, sebaceous gland tumors, and colorectal cancer [5].
• Brooke-Spiegler syndrome: This is a rare genetic disorder characterized by the development of multiple basal-cell carcinomas, trichoepitheliomas, and odontogenic keratocysts [7].
• Sotos syndrome: This is a rare genetic disorder characterized by accelerated growth in infancy and early childhood, often accompanied by developmental delays and distinctive facial features [4].
• Cutaneous T-Cell Lymphoma: This is a type of non-Hodgkin lymphoma that affects the skin, and can present with similar symptoms to NBCCS, such as multiple skin lesions [8].

It's worth noting that the differential diagnosis for NBCCS also includes other conditions that may not be directly related to cancer or genetic disorders, but rather to developmental anomalies or other systemic diseases.

References:

[1] Gorlin syndrome, also called Gorlin-Goltz syndrome, basal cell nevus syndrome (BCNS), or nevoid basal cell carcinoma syndrome, is an autosomal dominant familial cancer syndrome. It is characterized by numerous basal cell carcinomas (BCCs), along with skeletal, ophthalmologic, and neurologic abnormalities.

[2] Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age.

[3] Bazex syndrome is a rare genetic disorder characterized by the development of basal-cell carcinomas and palmoplantar keratodermas. It is often associated with mutations in the STS gene.

[4] Sotos syndrome is a rare genetic disorder characterized by accelerated growth in infancy and early childhood, often accompanied by developmental delays and distinctive facial features.

[5] Torre's syndrome (Muir-Torre's syndrome) is a rare autosomal dominant disorder that combines multiple basal cell carcinomas, sebaceous gland tumors, and colorectal cancer.

[7] Brooke-Spiegler syndrome is a rare genetic disorder characterized by the development of multiple basal-cell carcinomas, trichoepitheliomas, and odontogenic keratocysts.

[8] Cutaneous T-Cell Lymphoma is a type of non-Hodgkin lymphoma that affects the skin, and can present with similar symptoms to NBCCS, such as multiple skin lesions.