Nevoid Basal Cell Carcinoma Syndrome

Updated: Mar 29, 2017
  • Author: Daniel Berg, MD; Chief Editor: Dirk M Elston, MD  more...
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Overview

Background

Nevoid basal cell carcinoma syndrome (NBCCS) represents a series of multiorgan abnormalities known to be the consequence of abnormalities in the PTCH gene. The syndrome has been documented for 50 years, but more recent developments in molecular genetics have dramatically increased understanding of its pathophysiology and opened up molecular avenues for treatment in the future.

Go to Basal Cell Carcinoma for more complete information on this topic.

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Pathophysiology

Multiple organ systems may be impacted in nevoid basal cell carcinoma syndrome (NBCCS). Abnormalities of the skin, the skeletal system, the genitourinary system, and the central nervous system (CNS) are the most common. Other less common neoplasms and abnormalities are also associated with the disease and are well documented. [1]

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Etiology

NBCCS, also known as basal cell nevus syndrome (BCNS), is an autosomal dominant syndrome caused by mutations in the PTCH (patched) gene found on chromosome arm 9q. The disease has complete penetrance and variable expressivity. Although clinical features vary more among families than within families, no clear-cut link exists between specific mutations and phenotype. Approximately one third of cases are new mutations.

Genetics

First elucidated in fruit flies, the protein product of the PTCH gene is important in determining segment polarity of wings and limbs (anterior-posterior relationships in developing embryos). In mammals, PTCH is an important inhibitor in the so-called hedgehog (HH) signaling pathway, whose downstream proteins can lead to cell growth. PTCH is frequently mutated on 1 allele in sporadic basal cell carcinomas (BCCs), and according to Epstein, "upregulation of HH signaling is the pivotal abnormality in all BCCs." [2] . Its wide-reaching activity accounts for the myriad findings in patients with NBCCS. [3, 4, 5, 6, 7]

Ultraviolet exposure

Ultraviolet (UV) light exposure appears to be an important cofactor. BCCs are much more common in sun-exposed areas and are much more common in white individuals with the syndrome. Nevertheless, molecular genetic studies looking for UV-related mutations in BCCs obtained from patients with NBCCS leave the possibility that agents other than UV-B may cause alterations to the gene. [8]

Radiation

Patients are particularly sensitive to ionizing radiation (radiation therapy; XRT), and reports have described multiple BCCs in the radiation portal developing in patients treated with XRT for medulloblastoma. Reports of more aggressive BCCs occurring in sites of previous XRT for BCC also exist. Radiobiologic studies on fibroblasts suggest an abnormal response to radiation in fibroblasts obtained from patients with NBCCS.

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Epidemiology

The approximate prevalence of NBCCS is reported to be 1 case per 56,000-164,000 population. The prevalence is likely to be considerably higher in individuals younger than 20 years who present with BCCs.

The syndrome is found in all races, and men and women are affected about equally (1:1.3). However, a definite but smaller percentage of black individuals present with skin cancer and have fewer skin cancers than affected white individuals. This decreased number of skin cancers, a diagnostic hallmark, may account for the comparatively fewer patients with darker skin ascertained in reviews of the syndrome. The lone study evaluating an African cohort found that only 20% with NBCCS had basal cell carcinoma. [9] Recent Japanese data also showed a lower rate of skin cancer with a later age of onset compared with whites. [10] Full expression of the non–skin cancer features of the syndrome is found in patients of all skin types.

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Prognosis

Morbidity and premature mortality in nevoid basal cell carcinoma syndrome (NBCCS) are primarily related to the development of skin cancers and other tumors associated with the syndrome. Actual mortality rates are unavailable; morbidity from multiple skin cancers and their treatment may be severe.

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Patient Education

Patients with nevoid basal cell carcinoma syndrome (NBCCS) need information about the syndrome. Coping with the multiple BCCs and the required multiple treatments is often difficult, and patient counseling and support may be critical. Web sites exist with resources for patients with NBCCS (see BCCNS Life Support Network).

Patients should be educated about the hereditary nature of NBCCS, and they should have genetic counseling. In addition, with regard to skin cancer, patients should be advised to reduce UV light exposure, as well as advised about the relative risk and possible deleterious effects of receiving radiation therapy for their skin cancers or for other tumors as well.

With respect to other findings, patients should be counseled to look for symptoms referable to the CNS, the genitourinary system, the cardiovascular system, and dentition, as well as other potentially involved systems.

For patient education information, see the Cancer and Tumors Center, as well as Skin Cancer and Skin Biopsy.

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