Basal Cell Naevus Syndrome

Basal cell naevus syndrome is a rare inherited condition that causes multiple skin cancers to develop from a young age, along with cysts in the jaw and other abnormalities throughout the body.

Gorlin syndrome, Naevoid basal cell carcinoma syndrome, Basal cell carcinoma syndrome, Basal cell carcinoma naevus syndrome, Gorlin-Goltz syndrome, Nevoid basal cell carcinoma syndrome, NBCCS, MIM 109400

Q87.89

Table of contents

• What is basal cell naevus syndrome?
• Who gets basal cell naevus syndrome?
• What causes basal cell naevus syndrome?
• What are the features of basal cell naevus syndrome?
• How does the condition vary in different skin types?
• How is basal cell naevus syndrome diagnosed?
• How is basal cell naevus syndrome treated?
• What is the outlook?

What is basal cell naevus syndrome?

Basal cell naevus syndrome is a rare genetic cancer syndrome that causes multiple health problems affecting different parts of the body. The condition is characterized by the development of many basal cell carcinomas (a type of skin cancer), odontogenic keratocysts (cysts in the jawbones), and various other abnormalities^[1].

The syndrome is probably best known by its alternative name, Gorlin syndrome, named after the doctor who described the full spectrum of the disease in 1960^[4]. Unlike typical basal cell carcinomas that usually develop in older adults after years of sun exposure, people with this syndrome develop these skin cancers much earlier in life, often during their teenage years or early twenties^[1].

Who gets basal cell naevus syndrome?

Basal cell naevus syndrome is an autosomal dominant genetic disorder, meaning that if one parent has the gene mutation, each child has a 50% chance of inheriting it and developing the condition^[3]. The syndrome affects males and females equally^[1].

The condition is very rare, with estimates of prevalence ranging widely from 1 in 40,000 to 1 in 256,000 people^[1][2]. Although the syndrome is seen in all races, it is rarely diagnosed in Black Americans and Asians^[1][2]. This difference is partly because people with darker skin are much less likely to develop the skin cancers that often lead to diagnosis.

While the condition is present from birth, symptoms often don’t appear until childhood or adolescence. Most people develop noticeable signs in their teens or early adulthood^[6].

What causes basal cell naevus syndrome?

Basal cell naevus syndrome results from genetic mutations affecting the sonic hedgehog signaling pathway, which is crucial for proper cell growth and development^[1]. The genes most commonly involved are PTCH1, PTCH2, and SUFU. PTCH1 mutations are the most common, accounting for most cases^[1][2].

These genes normally work as tumor suppressor genes, meaning they help prevent tumors from forming. When mutations occur in these genes, cells can grow abnormally and form cancerous or non-cancerous growths^[7].

People with the syndrome inherit one mutated copy of the gene from birth. For cancer to develop, a second change must occur in certain cells during their lifetime. This second change can happen due to environmental factors such as sun damage or radiation exposure^[2][6].

In about 20 to 30 percent of cases, the mutation is not inherited but occurs spontaneously before birth as a new mutation^[2]. These individuals can then pass the mutation on to their children.

What are the features of basal cell naevus syndrome?

Basal cell naevus syndrome affects many different parts of the body. The condition is characterized by five major components as well as many other possible features^[4].

Skin features

The most common sign is the development of multiple basal cell carcinomas at an unusually young age. These skin cancers typically appear by age 20 and continue to develop throughout a person’s life^[1]. The cancers usually occur on sun-exposed areas like the face and neck, but they can also appear on sun-protected areas such as the genitals^[1].

The basal cell carcinomas appear as smooth rounded lumps, usually 1 to 15 millimeters in diameter. They may look like skin tags, moles, blood vessel growths, or tiny white bumps called milia^[1].

Between 60 and 87 percent of people with the syndrome develop small pits or indentations in the palms of their hands or soles of their feet. These pits often appear in childhood and are permanent^[1][4][6].

Jaw cysts

Odontogenic keratocysts in the jaw occur in 65 to 80 percent of people with basal cell naevus syndrome^[1][4]. These are usually found in the lower jaw (mandible) and typically appear during the second or third decade of life. The cysts are often painless but can cause the jaw to fracture or push teeth out of position^[1].

Skeletal abnormalities

About 65 to 70 percent of people with the syndrome have skeletal abnormalities^[4]. These include characteristic facial features such as an enlarged head, eyes that are spaced far apart, a broad nasal bridge, prominent forehead, and an enlarged lower jaw^[1].

Other skeletal problems include abnormal ribs (which may be split, spread apart, or fused together), curved spine, wedge-shaped vertebrae, extra or webbed fingers and toes, and chest deformities such as sunken or protruding chest^[1].

Brain and nervous system

In 65 to 70 percent of cases, a type of brain calcification called calcification of the falx cerebri can be seen on X-rays, usually by age 20^[1][4].

About 5 percent of people with basal cell naevus syndrome develop medulloblastoma, a cancerous brain tumor that typically occurs in childhood^[1]. People with SUFU gene mutations have a 20-fold higher risk of developing this brain tumor compared to those with PTCH1 mutations^[2].

Up to 5 percent of affected individuals may have intellectual disability^[1].

Other tumors

The syndrome increases the risk of developing fibromas, which are non-cancerous tumors made of connective tissue. Cardiac fibromas occur in 2 percent of children with the condition, while ovarian fibromas occur in 20 percent of females and are often bilateral and calcified^[1].

Eye problems

Various eye abnormalities can occur, including cloudy corneas, cataracts, glaucoma, crossed eyes, abnormal pigmentation of the retina, and in rare cases, congenital blindness^[1].

Other features

Additional features may include cleft lip and palate, high arched palate, enlarged breast tissue in males (gynecomastia), underdeveloped sex organs in males, abnormally shaped uterus, and lymphatic cysts in the abdomen^[1].

How does the condition vary in different skin types?

The appearance and frequency of basal cell carcinomas vary significantly depending on skin color. In people with pale skin, 80 to 90 percent develop multiple basal cell carcinomas^[1]. However, Black patients may have fewer than two skin cancers, and about 20 percent of dark-skinned Africans with the syndrome have none^[1].

Because people with darker skin are less likely to develop the characteristic skin cancers, they are more often diagnosed based on other features such as jaw cysts^[2]. This means the condition may be harder to identify in people with darker skin, and cases may be missed or diagnosed later.

How is basal cell naevus syndrome diagnosed?

Diagnosis is based on a combination of clinical features, family history, physical examination, and various tests^[4].

Healthcare providers will conduct careful skin and oral examinations to look for basal cell carcinomas and jaw abnormalities. They may recommend several imaging tests, including^[4]:

• Skull X-rays to check for brain calcification
• Chest X-rays to look for rib abnormalities
• Panoramic X-rays of the jaw to detect cysts
• Magnetic resonance imaging (MRI) of the brain
• Pelvic ultrasound in women to check for ovarian fibromas

Genetic testing is available to identify mutations in the PTCH1, PTCH2, or SUFU genes. This testing can confirm the diagnosis or test family members who may be at risk^[7].

Any unusual moles or growths on the skin may be biopsied to check for basal cell carcinoma^[3].

Because the condition can cause so many different problems, diagnosis and management often requires a team of specialists including dermatologists, oral surgeons, geneticists, neurologists, and other healthcare professionals.

How is basal cell naevus syndrome treated?

There is no cure for basal cell naevus syndrome, but symptoms can be managed with regular monitoring and appropriate treatment^[6][7].

Skin cancer treatment

Treatment focuses on removing basal cell carcinomas as they develop. Regular skin examinations are crucial for early detection^[1]. Several treatment options are available:

Mohs surgery is often the preferred treatment for basal cell carcinoma in people with this syndrome. This specialized surgical technique removes thin layers of tissue one at a time and examines them under a microscope until no cancer remains. This approach removes all the cancer while preserving as much healthy tissue as possible. Mohs surgery has the highest cure rate for basal cell carcinoma, with 99 percent of cases cured^[3].

Other treatment options include standard surgical excision, freezing (cryotherapy), or scraping away the cancerous tissue^[3]. Topical treatments with medications such as 5% imiquimod cream have shown success in treating basal cell carcinomas in some people with the syndrome^[9].

Radiation therapy is generally avoided when possible because it can trigger the development of additional basal cell carcinomas in people with this genetic condition^[1][2].

Jaw cyst treatment

Odontogenic keratocysts are usually treated by surgical removal. Because these cysts can recur, patients need regular follow-up with panoramic jaw X-rays to monitor for new cysts^[4].

Monitoring and surveillance

People with basal cell naevus syndrome need regular monitoring throughout their lives. This typically includes biannual skin examinations and annual panoramic jaw X-rays^[4]. Children should be monitored for brain tumors, especially those with SUFU mutations who have a higher risk.

Genetic counseling

Genetic counseling is recommended for affected individuals and their families to understand the inheritance pattern and risk to future children^[1][7].

What is the outlook?

With careful monitoring and early treatment, people with basal cell naevus syndrome can live normal lifespans^[6]. The condition doesn’t have to significantly impact quality of life when properly managed.

The main concerns are the ongoing development of basal cell carcinomas and the need for repeated treatments throughout life. However, basal cell carcinoma rarely spreads to other parts of the body when treated promptly^[1].

Taking extra care to prevent skin cancer is essential. This includes protecting skin from sun exposure by using broad-spectrum sunscreen with high SPF, wearing protective clothing including wide-brimmed hats, avoiding tanning beds completely, and limiting time in direct sunlight^[6].

Early diagnosis and treatment are important to reduce the severity of long-term complications, including cancer and jaw deformities^[4]. Regular screenings allow healthcare providers to catch and treat problems early when they are most manageable.