Naevoid Basal Cell Carcinoma Syndrome

Naevoid Basal Cell Carcinoma Syndrome

Also known as Gorlin Syndrome, Gorlin-Goltz Syndrome, Basal Cell Naevus Syndrome (BCNS), Basal Cell Cancer Syndrome (BCCS)

What is NBCCS?

NBCCS is a rare genetic disorder (prevalence between 1 in 31000 – 1 in 164000). In the majority of those affected, it is characterised by the widespread growth of multiple skin cancers (typically basal cell carcinomas) at a young age (age at first diagnosis ranges from 2 to 53 years old, with an average age of 20 to 21 years). Males and females are equally affected, with increased prevalence seen with a positive family history (an affected first degree relative with NBCCS – the altered gene is inherited in an autosomal dominant pattern).

The basal cell carcinomas (BCCs) can develop in all areas of the body, but are most prevalent in sun exposed areas – face, neck, ears, forearms, hands, and can develop into the hundreds and even thousands. Individuals with lighter skin colour are more likely to develop basal cell carcinomas than those with darker skin types. Affected individuals may also have multiple developmental abnormalities involving the spine, ribs, face, and jaw (odontogenic keratocysts), as well as an increased chance of developing brain tumours in early childhood (medulloblastoma).

What causes NBCCS?

NBCCS is due to changes (mutations) in the body’s genes (chromosomes).

NBCCS is most commonly caused by mutations involving PTCH1 (gene) on chromosome 9q22.3, and SUFU (gene) on chromosome 10q24.32.

PTCH1 mutations lead to increased abnormal tissue (tumour) growth which result in the development of multiple tumours in the form of skin cancers (BCC).

SUFU mutations appear to be associated with milder clinical features (less BCCs and no jaw cysts), but with a greatly increased chance of developing a malignant childhood brain tumour (medulloblastoma).

What does NBCCS look like?

Characteristic facial features include a prominent forehead (frontal bossing), broad nose, and a widened distance between the eyes (hypertelorism).

NBCCS is characterised by the widespread development of multiple BCCs, and small indents or pits on the palms and soles (palmoplantar pits).

BCCs occur more commonly on sun exposed areas, but can occur in any location.

Pits appear as sharply bordered, shallow lesions, ranging from 1-2mm in size. These become more visible after soaking the hands and feet in warm water for 10-15 minutes.

What other problems can occur with NBCCS?

Along with developmental abnormalities, NBCCS can present in many ways. In children, the first sign may be medulloblastoma. The presentation of NBCCS is outlined as Major and Minor Criteria, which serves as an aid in diagnosis.

Major Criteria include

  • > 2 BCCs or 1 BCC < 20 years of age
  • Jaw cyst (proven histologically as an odontogenic keratocyst or a polycystic bone cyst)
  • ≥ 3 palmar or plantar pits
  • Central Nervous System Abnormalities
    • sheet like (lamellar) calcification of the falx cerebri <20 years of age
  • Family History (first degree relative with NBCCS)

Minor Criteria include

  • Childhood brain tumour (medulloblastoma)
  • Large Head or macrocephaly (>97th percentile)
  • Developmental Abnormalities
    • cleft lip or palate
    • prominent forehead (frontal bossing)
    • broad nose
    • widened distance between the eyes (hypertelorism)
  • Bone Abnormalities
    • Rib Abnormalities – double (bifid), thickened (fused), or spread widely apart (splayed) ribs
    • Chest Abnormalities – hollow depression of central chest (pectus excavatum)
    • Hand Abnormalities – fused fingers (syndactyly), extra fingers (polydactyly)
    • Spinal Abnormalities – increased bend of the spine (scoliosis or kyphosis)
  • Bone Abnormalities on X-ray
    • Abnormal bones in the spine (hemivertebrae)
    • Abnormal pattern of growth in bones of hands and feet
      • Shorter fourth finger (short fourth metacarpal)
      • Extra fingers (polydactyly)
      • Fingers fused together (syndactyly)
    • Abnormal Growth in Reproductive Organs
      • Female – ovarian fibroma
      • Male – undescended testes
    • Cardiac Fibroma (benign growth in heart)
    • Ocular (eye) Anomalies
      • Cataract
      • Small eye (microphthalmos)
      • Iris tumour (coloboma)
    • Lympho-mesenteric or pleural cysts

How is NBCCS diagnosed?

The diagnosis is usually made by a dermatologist after reviewing the presentation of the individual (clinical diagnosis).

The clinical diagnosis is based on the presence of either

  • 2 major criteria, or
  • 1 major criteria and 2 minor criteria

How is NBCCS treated?

The condition of NBCCS is characterised by the development of a large number of skin cancers (BCCs) throughout an individual’s lifetime.  In general, they are best treated by excision. Due to the large number of excisions at an early age, considerable scarring and disfigurement may result. Consideration may be given to the treatment of superficial BCCs with measures including curette and cautery, 5% topical fluorouracil, 5% imiquimod, and photodynamic therapy (PDT). Radiation therapy is not recommended for BCC treatment in NBCCS, as the ionizing radiation may trigger the development of more BCCs. Ongoing lifetime surveillance is required for the development of new BCCs.

A multidisciplinary approach is recommended for syndrome related abnormalities, and complications arising from tumours that develop in other systems.

For surveillance of NBCCS individuals, guidelines include:

In carriers of PTCH1 mutations (low risk of medulloblastoma):

  • Annual dermatologist review (if diagnosed) from age 10, more frequent after first diagnosis of BCC
  • Heart scan (baseline echocardiogram) in infancy
  • Dental examination with jaw x-ray every 12 to 18 months, starting at age 8
  • Ovarian ultrasound by age 18
  • Imaging tests for brain abnormalities (medulloblastoma) only if symptoms present

In carriers of SUFU mutations (high risk of medulloblastoma):

  • Same as PTCH1 carriers, except
  • No jaw x-ray (as jaw cysts have not been observed)
  • Screening imaging tests for brain abnormalities (medulloblastoma)
    • Brain magnetic resonance imaging (MRI) every fourth month through to age 3, then
    • Brain MRI every sixth month until age 5

Recently, medical therapies to target gene mutations (vismodegib and sonidegib) have shown promise for BCC treatment in NBCCS. Both these medications are listed on the Pharmaceutical Benefits Scheme subject to certain qualifying criteria.

What is the likely outcome of NBCCS?

NBCCS individuals should be counselled about the importance of minimising sun exposure, as solar radiation exacerbates the existing predisposition for BCC development.

NBCCS individuals may be vitamin D deficient, and may require vitamin D supplementation.

NBCCS is generally not associated with an increased mortality, although individuals may experience increased morbidity from serial BCC excisions and the complications from associated tumours.

Further information about NBCCS can be found on

  • DermNet NZ
  • The BCCNS Alliance
  • The Gorlin Syndrome Group
  • The Australian Gorlin Syndrome Mutual Support Group

This information has been written by Dr Rudy Yeh (MBBS MS), Dr David Wong (FACD)

This page was last updated February 2019

  • Disclaimer

    2018 © Australasian College of Dermatologists.

    You may use for personal use only. Please refer to our disclaimer.