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Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.

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Nevoid Basal Cell Carcinoma Syndrome

Synonyms: Basal Cell Nevus Syndrome (BCNS), Gorlin Syndrome, NBCCS

, MD, FRCP and , MD, FRCP.

Author Information
, MD, FRCP
Central Manchester NHS Foundation Trust Regional Genetic Service
St Mary's Hospital
Consultant in Medical Genetics, St Mary's Hospital and Christie Hospital
Professor in Medical Genetics, Manchester University
Manchester, United Kingdom
, MD, FRCP
Clinical Genetics Unit
Birmingham Women's Hospital
Consultant Clinical Geneticist, West Midlands Regional Genetics Service
Professor of Clinical Genetics, University of Birmingham
Birmingham, United Kingdom

Initial Posting: ; Last Update: March 7, 2013.

Summary

Disease characteristics. Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by the development of multiple jaw keratocysts, frequently beginning in the second decade of life, and/or basal cell carcinomas (BCCs) usually from the third decade onward. Approximately 60% of individuals have a recognizable appearance with macrocephaly, bossing of the forehead, coarse facial features, and facial milia. Most individuals have skeletal anomalies (e.g., bifid ribs, wedge-shaped vertebrae). Ectopic calcification, particularly in the falx, is present in more than 90% of affected individuals by age 20 years. Cardiac and ovarian fibromas occur in approximately 2% and 20% of individuals respectively. Approximately 5% of children with NBCCS develop medulloblastoma (primitive neuroectodermal tumor [PNET]), generally the desmoplastic subtype. Peak incidence is at age two years. Life expectancy in NBCCS is not significantly different from average.

Diagnosis/testing. In most individuals, the diagnosis of NBCCS is established using clinical diagnostic criteria. PTCH1 (formerly PTCH) is the only gene in which mutations are known to cause NBCCS.

Management. Treatment of manifestations: Best provided by specialists experienced with the condition; surgical excision for keratocysts identified early in life; early treatment of BCCs to ensure their complete eradication and to preserve normal tissue to prevent disfigurement; preservation of ovarian tissue whenever ovarian fibromas require surgical treatment.

Prevention of primary manifestations: Avoidance of radiotherapy unless alternative therapies are unavailable; use of diagnostic x-rays sparingly; avoidance of direct sun exposure through the use of complete sun block and covering of exposed skin with long sleeves, high collars, and hats.

Surveillance: Monitoring of head circumference throughout childhood; developmental assessment and physical examination every six months in the first years of life because of increased risk for medulloblastoma; in those over age eight years, orthopantogram every 12-18 months to identify jaw keratocysts; skin examination at least annually.

Evaluation of relatives at risk: Because of the need for surveillance for complications of NBCCS (medulloblastoma in children; jaw cysts and BCCs in adults) and the need to avoid sun exposure, clarification of the genetic status of at-risk relatives, including children, is appropriate.

Genetic counseling. NBCCS is inherited in an autosomal dominant manner. Approximately 70%-80% of probands have inherited the condition from a parent and approximately 20%-30% of probands have a de novo mutation. Offspring of an affected individual are at a 50% risk of inheriting NBCCS. Prenatal testing for pregnancies at increased risk is possible if the disease-causing mutation has been identified in an affected family member.

Diagnosis

Clinical Diagnosis

Nevoid basal cell carcinoma syndrome (NBCCS) is diagnosed in individuals with two major diagnostic criteria and one minor diagnostic criterion or one major and three minor diagnostic criteria [Evans et al 1993]. A similar series of diagnostic criteria was proposed by Kimonis et al [1997]. No study has been able to assess which combination of diagnostic criteria represents the best trade-off between sensitivity and specificity.

Although a typical facial gestalt is present in most individuals with NBCCS, measurement of head circumference and examination of the skin for basal cell carcinomas (BCCs), nevi, milia, and plantar/palmar pits is necessary for clinical diagnosis.

The availability of molecular genetic testing has broadened the phenotypic spectrum of NBCCS and, thus, individuals who do not fulfill all diagnostic criteria may be found to have a pathogenic PTCH1 (formerly PTCH) mutation. (An individual who is the first in the family to be affected may have milder signs because of somatic mosaicism.)

Major criteria

  • Lamellar (sheet-like) calcification of the falx or clear evidence of calcification in an individual younger than age 20 years. Falx calcification is nearly always present and is visible on anteroposterior (AP) x-rays (see Note re radiographs) of the skull after age 20 years. (Sella calcification, when present, is visible on lateral x-rays of the skull.)
  • Jaw keratocyst (odontogenic keratocyst histologically; seen on orthopantogram as an area of translucency)
  • Palmar/plantar pits (two or more); particularly useful in diagnosis and more pronounced when the hands and feet are soaked in warm water for up to ten minutes. Pits may appear as white "punched-out" or pink "pin-prick" lesions.
  • Multiple BCCs (>5 in a lifetime) or a BCC before age 30 years. Provision needs to be made for decreased risk of BCC in dark-skinned races and increased risk in whites living in hot sunny climates.
  • First-degree relative with NBCCS

Minor criteria

  • Childhood medulloblastoma (also called primitive neuroectodermal tumor [PNET])

    Note: A consensus meeting consisting of US-based experts (with one French participant) has suggested changing medulloblastoma to a major criteria and allowing the diagnosis of NBCCS with only two minor criteria in addition to a major criterion [Bree et al 2011]. The concern would be that this would reduce the specificity of diagnostic criteria, as medulloblastoma cases undergoing radiotherapy without NBCCS are likely to develop more than one BCC. Confining the medulloblastoma diagnosis to nodular/desmoplastic and disallowing BCCs occurring after radiotherapy as a major criterion may improve sensitivity without losing specificity.
  • Lympho-mesenteric or pleural cysts
  • Macrocephaly (OFC >97th centile)
  • Cleft lip/palate
  • Vertebral/rib anomalies observed on chest x-ray and/or spinal x-ray (see Note re radiographs): bifid/splayed/extra ribs; bifid vertebrae
  • Preaxial or postaxial polydactyly
  • Ovarian/cardiac fibromas
  • Ocular anomalies (cataract, developmental defects, and pigmentary changes of the retinal epithelium)

Note re radiographs: To verify a clinical diagnosis of NBCCS, AP and lateral x-rays of the skull, an orthopantogram, chest x-ray, and spinal x-ray are usually necessary.

  • Clinicians should avoid using x-rays in childhood if the diagnosis is obvious without them or if a known mutation exists in the family.
  • If radiographs have already been taken (i.e., before the diagnosis of NBCCS is being considered) it is preferable to obtain and review the original radiographs rather than repeat them because individuals with NBCCS are susceptible to x-irradiation.
  • Even when present, bifid ribs, bifid vertebrae, and falx calcification are often not mentioned in formal reports of radiographic findings, as these can also be normal variations in the general population.
  • X-ray findings may be helpful in suggesting or confirming the diagnosis in young children with cardiac fibromas, cleft lip/palate, polydactyly, or macrocephaly [Debeer & Devriendt 2005, Veenstra-Knol et al 2005].

Testing

Cytogenetic analysis. Although chromosomal translocations or large cytogenetically detectable deletions on chromosome 9 have been reported in a small number of individuals with NBCCS, chromosome analysis is rarely likely to be helpful in diagnosis.

A 9q deletion should be considered when both of the following are present:

  • Clinical features consistent with NBCCS
  • Additional features, including severe developmental delay or short stature

Presence of the latter features suggests that additional chromosomal material has been lost.

Molecular Genetic Testing

Gene. PTCH1 (formerly PTCH) is the only gene in which mutations are known to cause NBCCS.

Clinical testing

Table 1. Summary of Molecular Genetic Testing Used in Nevoid Basal Cell Carcinoma Syndrome

Gene 1Test MethodMutations DetectedMutation Detection Frequency by Test Method 2
PTCH1Sequence analysis 3Sequence variants50%-85% 4
Deletion/duplication analysis 5 (Multi)exonic and whole-gene deletions 6%-21% 6
Linkage analysis Not applicableNot applicable 7

1. See Table A. Genes and Databases for chromosome locus and protein name.

2. The ability of the test method used to detect a mutation that is present in the indicated gene

3. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations; typically, exonic or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4. Sequence analysis of exons 2-23 with intron-exon junctions and one of the splice forms of exon 1 detects mutations in 50%-85% of individuals with typical clinical findings of NBCCS. Individuals and families with no other features apart from multiple BCCs have a very small probability of having a PTCH1 mutation [Klein et al 2005, Marsh et al 2005].

5. Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.

6. Eight of 38 individuals with NBCCS had large deletions that were not identified using sequence analysis [Nagao et al 2011].

7. If the family pedigree structure is sufficient and family members cooperate with the testing process, linkage analysis may be performed to confirm cosegregation of a potential pathogenic mutation with disease in individual families. Linkage testing cannot be used to confirm the diagnosis of NBCCS.

Test characteristics. Information on test sensitivity, specificity, and other test characteristics can be found online [Lo Muzio et al 2013; click here for full text].

Interpretation of test results

  • Missense mutations are relatively common and it may be difficult to determine whether they are pathologic or benign in an individual who has no family history of NBCCS and does not fulfill diagnostic criteria. However, demonstrating that the missense mutation is de novo in the absence of a known family history is supportive of pathogenicity.
  • The identification of an inactivating allele that is highly likely to be pathologic (e.g., nonsense, frameshift deletion/insertion, splice site mutation) confirms a clinical diagnosis of NBCCS. Because some individuals with a clinical presentation consistent with NBCCS do not have PTCH1 mutations detectable by routine techniques, failure to detect one does not exclude the diagnosis of NBCCS.
  • The sensitivity of the testing depends on both the test methods and the diagnostic criteria used. Low mutation detection rate in some studies may reflect the clinical diagnostic criteria rather than the molecular testing strategy [Boutet et al 2003].
  • The likelihood of detecting a mutation may be lower in an individual who is known to be the first affected in the family, possibly because a de novo mutation has resulted in somatic mosaicism in that individual. In such cases, the likelihood of detecting a mutation is increased if the person tested is an affected child of an individual who has mild features of NBCCS.
  • The same PTCH1 mutation present in two or more tumors but not present (or present at a lower-than-normal ratio) in lymphocyte DNA strongly suggests somatic mosaicism.

Testing Strategy

To confirm/establish the diagnosis in a proband. Molecular genetic testing can be used to confirm the diagnosis in individuals with atypical clinical findings. Testing of lymphocyte DNA with direct sequencing of all exons can be followed by deletion/duplication analysis.

In individuals suspected of having the somatic mosaic form of NBCCS it is probably better to initially test a tumor (e.g., an accessible BCC). Identification of an identical mutation in two separate tumors, even if not found in lymphocytes, confirms the presence of mosaicism [Evans et al 2007].

Predictive testing for at-risk asymptomatic adult family members requires prior identification of the disease-causing mutation in the family.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the disease-causing mutation in the family.

Clinical Description

Natural History

More than 100 features that are variable within and among families have been associated with nevoid basal cell carcinoma syndrome (NBCCS) [Farndon 2004].

Findings in their usual order of manifestation:

  • Appearance. Approximately 60% of individuals with a PTCH1 mutation have a recognizable appearance with macrocephaly, bossing of the forehead, coarse facial features, and facial milia. The shoulders slope downward.
  • Macrocephaly. The first feature likely to be observed is relative macrocephaly. A large proportion of babies with NBCCS require delivery by caesarean section because of large head size. After birth, the head growth pattern often resembles that of arrested hydrocephalus, but hydrocephaly requiring treatment is rare. Head circumference increases above the 97th centile until age ten to 18 months and then maintains its centile.

    There is often some delay in motor milestones; most individuals catch up by about age five years. No published psychometric evidence for global delay exists.
  • Birth defects. Most individuals have skeletal anomalies identified on radiographs (e.g., bifid ribs, wedge-shaped vertebrae). Severe skeletal defects resulting from multiple rib/vertebral anomalies have been reported but are uncommon, as is open spina bifida.

    Ectopic calcification, particularly in the falx, is present in more than 90% of individuals by age 20 years [Ratcliffe et al 1995, Kimonis et al 2004].

    Congenital malformations, found in approximately 5%, include cleft lip/palate (5%), polydactyly, and severe eye anomalies. Eye findings include strabismus, cataract, orbital cyst, microphthalmia, and pigmentary changes of the retinal epithelium [Black et al 2003, Ragge et al 2005].
  • Medulloblastoma. Approximately 5% of individuals with NBCCS develop the childhood brain malignancy medulloblastoma (now often called primitive neuroectodermal tumor [PNET]) [Cowan et al 1997]. The tumor tends to be of desmoplastic histology [Amlashi et al 2003] and to have a favorable prognosis. Peak incidence of medulloblastoma in NBCCS is at approximately age two years, compared to seven years in its sporadic form [Cowan et al 1997, Amlashi et al 2003].
  • Jaw keratocysts. Approximately 90% of affected individuals develop multiple jaw keratocysts. They can occur as early as age five years, but the peak occurrence is in the teenage years. Jaw keratocysts usually present as painless swellings. Untreated, they can lead to major tooth disruption and fracture of the jaw. Jaw cysts rarely occur after age 30 years.

    A rare malignant transformation of a keratocyst called ameloblastoma has been reported in individuals with NBCCS at least six times [Ponti et al 2012].
  • BCCs. Brownish/pink/orange basal cell nevi may occur in early childhood and may lie quiescent without evidence of aggressive behavior. The histologic appearance is that of a typical BCC which, when excised, can be the first, unexpected finding of NBCCS in simplex cases (i.e., affected individuals with no known family history of NBCCS), especially children. Active BCCs may grow from existing basal cell nevi that may be numerous, or typical BCCs may appear from virtually blemish-free skin. BCCs may also crust, bleed, and ulcerate, or may present as a localized infection.

    BCCs can occur in early childhood, but in general do not present until the late teens or early adulthood. They occur more frequently with age, although 10% of individuals with NBCCS never develop a BCC. Individuals with type 1 skin (white skin that burns, but never tans, e.g., Celtic skin) and individuals with excessive ultraviolet light exposure seem especially prone to developing large numbers of BCCs. Clinically, some affected individuals seem to be particularly radiosensitive, with new BCCs appearing in the field of radiation following radiotherapy.

Other skin manifestations include facial milia, which can be numerous, and meibomian cysts in the eyelids. Sebaceous cysts and dermoid cysts are also common. Skin tags (especially around the neck) often have the histologic appearance of BCCs but do not act aggressively.

Other tumors. Cardiac and ovarian fibromas occur, respectively, in approximately 2% and 20% of females [Evans et al 1993, Gorlin 2004]. Cardiac fibromas are usually present at birth or soon after. They can be asymptomatic or can cause arrhythmia or obstruction of cardiac flow. Rhabdomyomas may occur at other sites as well as in the heart [Watson et al 2004].

Ovarian fibromas are usually an incidental finding on ultrasound examination or at caesarean section. They may cause torsion of the ovary but are not thought to affect fertility. They can become large and calcified; however, malignant transformation is uncommon.

The risk of other malignant tumors is not clearly increased, although lymphoma [Pereira et al 2011] and meningioma have been reported [Kijima et al 2012].

Morbidity/mortality. Life expectancy in NBCCS is not significantly different from average [Wilding et al 2012]. The major problem is with the cosmetic effect of treatment of multiple skin tumors and usually, to a lesser extent, treatment of jaw keratocysts. A poor cosmetic outcome can lead to social difficulties, including difficulty maintaining employment.

Genotype-Phenotype Correlations

Early reports did not find a genotype-phenotype correlation [Wicking et al 1997]. In particular there is no evidence for genotype affecting age at onset of BCCs [Jones et al 2011]. Predictions about clinical severity are not yet possible for specific PTCH1 mutations, which are likely to be modified by the effects of other genes.

A large deletion has been identified in a family with an array of ophthalmic features, including a retinal pigmentary abnormality [Black et al 2003].

9q22.3 microdeletion syndrome. Large chromosomal deletions that involve PTCH1 are the cause the 9q22.3 microdeletion syndrome. This syndrome is characterized by developmental delay and/or intellectual disability, metopic craniosynostosis, obstructive hydrocephalus, pre- and postnatal macrosomia, and seizures, in addition to the features of NBCCS [Muller et al 2012].

Penetrance

Although NBCCS shows intra- and interfamilial variation in expression, experience clinically and from molecular testing is compatible with complete penetrance [Author, personal observation].

Anticipation

No evidence of anticipation has been reported. Variable expressivity explains the instances in which children appear more severely affected than a parent.

Prevalence

Few studies of disease prevalence exist. The most quoted prevalence figure, 1:57,000, comes from a study of a UK population of four million in northwest England [Evans et al 1991b]. Since publication of the study, an increased awareness of NBCCS and consequent increased diagnosis has led to a revision of that figure to nearer to 1:30,827 [Evans et al 2010]. The true figure may be even higher, as milder cases may not be recognized.

A study in Australia gave a minimum prevalence of 1:164,000 [Shanley et al 1994].

Birth incidence has recently been confirmed to be as high as 1:18,976 [Evans et al 2010].

Differential Diagnosis

The differential diagnosis depends on the mode of presentation.

Macrocephaly. If the proband is a baby with macrocephaly and other birth defects, a limited number of overgrowth syndromes including Sotos syndrome and Beckwith-Wiedemann syndrome need to be considered:

  • Sotos syndrome is characterized by a typical facial appearance, intellectual impairment, and overgrowth (increased height and head circumference). It is associated with neonatal jaundice, scoliosis, seizures, strabismus, conductive hearing loss, congenital cardiac anomalies, renal anomalies, and behavioral problems. The risk of sacrococcygeal teratoma and neuroblastoma is slightly increased. Approximately 80%-90% of individuals with Sotos syndrome have a demonstrable mutation or deletion of NSD1. Sotos syndrome is inherited in an autosomal dominant manner, with more than 95% of individuals having a de novo mutation.
  • Beckwith-Wiedemann syndrome is a disorder of growth characterized by macrosomia (large body size), macroglossia, visceromegaly, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, rhabdomyosarcoma), omphalocele, neonatal hypoglycemia, ear creases/pits, adrenocortical cytomegaly, and renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly). Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues. The diagnosis relies primarily on clinical findings, but molecular genetic testing reveals diagnostic changes in some affected individuals.
  • Isolated hydrocephaly or megalencephaly may be distinguished by clinical examination, family history, and x-rays.

Basal cell carcinomas (BCCs). If the initial presentation is multiple BCCs, clinical examination and radiographs should nearly always establish the diagnosis of NBCCS. Other inherited disorders with similar skin findings include the following:

  • Brooke-Spiegler syndrome, characterized by trichoepitheliomas, milia, and cylindromas presenting in the second or third decade and inherited in an autosomal dominant manner (OMIM 605041). The milia are miniature trichoepitheliomas and appear only in sun-exposed areas.
  • Bazex syndrome, characterized by multiple BCCs, follicular atrophoderma on the dorsum of hands and feet, decreased sweating, and hypotrichosis (OMIM 301845). The pitting on the backs of the hands is reminiscent of orange peel and quite unlike the palmar and plantar pits of NBCCS. The inheritance pattern is either autosomal dominant or X-linked dominant.
  • Rombo syndrome, a dominantly inherited condition similar to Bazex syndrome, reported in a single family (OMIM 180730). Skin findings are vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, BCCs, and peripheral vasodilation with cyanosis. The skin is normal until later childhood; BCCs develop in adulthood. Sweating is normal.
  • An autosomal dominant or X-linked dominant syndrome of hypotrichosis and BCCs reported in a single family [Oley et al 1992] (OMIM 301845)
  • Autosomal dominant inheritance of multiple basal cell carcinomas in the absence of other features

Acquired causes of multiple BCCs include arsenic exposure.

Jaw keratocysts. If the initial presentation is jaw keratocysts, clinical examination and radiographs should nearly always establish the diagnosis of NBCCS. In addition to examination of the child, a medical history and examination of the parents is advised.

Medulloblastoma. Children presenting with medulloblastoma need to be assessed for NBCCS, particularly if they are younger than age three years and/or have desmoplastic histology. In addition to examining the child, a medical history and examination of the parents is advised.

Children with nodular or desmoplastic medulloblastoma also need to be assessed for mutations in SUFU [Brugières et al 2012]. Brugières and colleagues demonstrated that 3/3 individuals with nodular meduloblastoma and 4/20 individuals with desmoplastic medulloblastoma caused by mutations in SUFU had some features of NBCCS. Furthermore, mutations in SUFU are associated with macrocephaly and 1/8 individuals with SUFU mutations who had medulloblastoma developed BCCs in the radiation field [Brugières et al 2012].

Note to clinicians: For a patient-specific ‘simultaneous consult’ related to this disorder, go to Image SimulConsult.jpg, an interactive diagnostic decision support software tool that provides differential diagnoses based on patient findings (registration or institutional access required).

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with nevoid basal cell carcinoma syndrome (NBCCS), the following evaluations are recommended:

  • Baseline measurement of head circumference, preferably with plotting on a chart that accounts for height. Evidence of rapid increase in centiles should prompt further investigation to exclude hydrocephalus.
  • Physical examination for birth defects of clinical significance (e.g., orofacial clefting, polydactyly)
  • X-rays to evaluate for rib and vertebral anomalies and falx calcification
  • Evaluation by a dentist or orthodontist familiar with NBCCS; jaw x-ray (orthopantogram) in individuals age eight years or older to evaluate for jaw keratocysts and other anomalies
  • Skin examination by a dermatologist familiar with NBCCS
  • Ophthalmologic evaluation for evidence of cataract, developmental defects, and pigmentary changes of the retinal epithelium
  • Ultrasound examination of the ovaries to evaluate for ovarian fibromas prior to pregnancy
  • Echocardiography in the first year of life to evaluate for cardiac fibromas
  • Medical genetics consultation

Because mesenteric and pleural cysts are rare, evaluation is not necessary in the absence of symptoms.

Treatment of Manifestations

Manifestations should be treated by specialists (e.g., oral surgeon, dermatologist, plastic surgeon, pediatrician, medical geneticist) experienced with the condition.

Keratocysts usually require surgical excision.

Early treatment of BCCs is essential to prevent long-term cosmetic problems, particularly on the face. The priorities are to ensure complete eradication of aggressive BCCs, and to preserve normal tissue to prevent disfigurement. Surgical excision is supplemented by a number of other possible treatments including cryotherapy and laser treatment for early lesions and photodynamic therapy. Surgical treatment using Mohs' microsurgery [Mohs et al 1980] appears particularly effective.

Systemic treatment with retinoids (e.g., etretinate) is possible but often not well tolerated.

Cardiac fibromas may be asymptomatic and can be monitored by a pediatric cardiologist.

If ovarian fibromas require surgical treatment, preservation of ovarian tissue is recommended, although it involves a risk of recurrence [Seracchioli et al 2001].

Prevention of Primary Manifestations

Use of radiotherapy can lead to the development of thousands of BCCs in the radiation field [Strong 1977, Evans et al 1991a] and therefore should be avoided if there are alternative treatments, especially in childhood. If the treating team believes that no other treatment modality is possible, radiotherapy should be used through as few skin ports as possible.

Diagnostic x-rays should be used sparingly.

Individuals with NBCCS should be advised to avoid direct sun exposure as much as possible. Excessive sun exposure increases the likelihood of developing BCCs. Affected individuals should cover up exposed skin by wearing long sleeves, high collars, and hats; complete sunblock should be used.

Surveillance

Head circumference should be followed throughout childhood and plotted on appropriate growth charts. Rapid enlargement should prompt evaluation for possible hydrocephalus.

Awareness of the risk of medulloblastoma in the first years of life is important and may justify developmental assessment and physical examination every six months. No evidence for the efficacy of regular neuroimaging exists; frequent computer tomography (CT) should be avoided because of risks associated with radiation sensitivity. A recent consensus meeting has suggested annual head MRI scans until age eight years in affected children [Bree et al 2011], but this would require general anesthesia for many children.

No other tumors occur at a frequency that warrants surveillance above that offered to members of the general population.

Orthopantogram is indicated every 12-18 months in individuals older than age eight years to identify jaw keratocysts.

Skin should be examined at least annually; some physicians recommend skin examination by a professional every three to four months.

Agents/Circumstances to Avoid

See Prevention of Primary Manifestations.

Evaluation of Relatives at Risk

Because of the need for surveillance for complications of NBCCS (most notably medulloblastoma in children and jaw cysts and BCCs in adults) and the need for sun screening, clarification of the genetic status of at-risk relatives, including children, is appropriate.

  • Molecular genetic testing is possible if a pathologic mutation has been identified in an affected family member.
  • Clinical examination and x-rays of the skull for calcification may be less likely to clarify the genetic status in a very young child because of the age-related features of NBCCS.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Since individuals with NBCCS have a large head circumference, a woman who is carrying an affected fetus should be assessed for the need for either early induction of labor or caesarean section delivery due to cephalopelvic disproportion.

Therapies Under Investigation

Photodynamic therapy (with infra-red light) showed early promise and appears safe [Haylett et al 2003]. A recent study showed outcomes in 33 individuals with NBCCS treated with PDT with a close to 60% control rate [Loncaster et al 2009].

Aminolevulinic acid has been investigated [Itkin & Gilchrest 2004, Oseroff et al 2005]. It is usually used in conjunction with PDT [Loncaster et al 2009].

Topical treatment with 5-fluorouracil (Efudex®) or imiquimod (5%) has been investigated [Kagy & Amonette 2000, Marks et al 2001, Stockfleth et al 2002]. A recent review suggested control rates approaching 90% for superficial BCCs and 50% for aggressive or nodular BCCs with imiquimod [Alessi et al 2009].

Topical 5-fluorouracil appears effective for superficial multicentric BCCs without follicular involvement but should not be used for deeply invasive BCCs.

Recently topical use of sonic hedgehog antagonists has entered clinical trials and is showing promise [Saran 2010]. Systemic use of sonic hedgehog antagonists in individuals with NBCCS who have advanced or refractory BCCs has also been effective [Sekulic et al 2012, Tang et al 2012], with a 43% response rate in 63 affected individuals with locally advanced BCCs. Response rates were very high in individuals with NBCCS but 53% discontinued therapy due to adverse side effects [Tang et al 2012]. A recent case report suggests that anti sonic hedgehog agents may also resolve keratocysts when given for BCC treatment [Goldberg et al 2011].

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Nevoid basal cell carcinoma syndrome (NBCCS) is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

  • Approximately 70%-80% of individuals diagnosed with NBCCS have an affected parent.
  • Approximately 20%-30% of probands have a de novo mutation.
  • Recommendations for the evaluation of parents of a proband with an apparent de novo mutation include a detailed skin examination, AP and lateral x-rays of the skull, chest x-ray, and spine x-ray. Molecular genetic testing can be used to clarify the genetic status of a parent when a PTCH1 mutation has been identified in the proband or other affected family member.

Note: (1) Although 70%-80% of individuals diagnosed with NBCCS have an affected parent, the family history may appear to be negative as a result of failure to recognize the disorder in family members because of variable expressivity. (2) If the parent is the individual in whom the mutation first occurred, s/he may have somatic mosaicism for the mutation, and may be mildly/minimally affected.

Sibs of a proband

Offspring of a proband

Other family members

  • The risk to other family members depends on the genetic status of the proband's parents.
  • If a parent is affected, his or her family members are at risk.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Genetic cancer risk assessment and counseling. For comprehensive descriptions of the medical, psychosocial, and ethical ramifications of identifying at-risk individuals through cancer risk assessment with or without molecular genetic testing, see Elements of Cancer Genetics Risk Assessment and Counseling (part of PDQ®, National Cancer Institute).

Considerations in families with an apparent de novo mutation. When neither parent of a proband with an autosomal dominant condition has the disease-causing mutation or clinical evidence of the disorder, it is likely that the proband has a de novo mutation. However, possible non-medical explanations including alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption could also be explored.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.

Predictive testing of individuals during childhood. Because of the need for surveillance for complications of NBCCS (most notably medulloblastoma) during childhood, clarification of the genetic status of at-risk individuals during childhood is appropriate. Clinical examination and x-rays of the skull for calcification may be less likely to clarify the genetic status in a very young child because of the age-related features of NBCCS. Molecular genetic testing may be considered if a pathologic mutation has been identified in an affected family member.

Predictive testing of adults. Clinical examination and x-rays frequently act as a "genetic test" in an apparently unaffected individual. Individuals need to be aware of the predictive implications of these examinations as well as those of molecular genetic testing of PTCH1.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

If the disease-causing mutation has been identified in the family, prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis (usually performed at ~15-18 weeks’ gestation) or chorionic villus sampling (usually performed at ~10-12 weeks’ gestation).

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Requests for prenatal testing for conditions which (like NBCCS) do not affect intellect, have variable expression, and have some treatment available are not common. Differences in perspective may exist among medical professionals and in families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although most centers would consider decisions about prenatal testing to be the choice of the parents, discussion of these issues is appropriate.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which the disease-causing mutation has been identified.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • BCCNS Life Support Network
    PO Box 321
    Burton OH 44021
    Phone: 866-834-1895 (toll-free); 440-834-0011
    Fax: 440-834-0132
    Email: info@bccns.org
  • Gorlin Syndrome Group
    11 Blackberry Way
    Preston Lancashire PR1 9LQ
    United Kingdom
    Phone: +44 1772 496849
    Email: info@gorlingroup.org

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A. Nevoid Basal Cell Carcinoma Syndrome: Genes and Databases

Gene SymbolChromosomal LocusProtein NameLocus SpecificHGMD
PTCH19q22​.32Protein patched homolog 1PTCH1 homepage - Mendelian genesPTCH1

Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B. OMIM Entries for Nevoid Basal Cell Carcinoma Syndrome (View All in OMIM)

109400BASAL CELL NEVUS SYNDROME; BCNS
601309PATCHED, DROSOPHILA, HOMOLOG OF, 1; PTCH1

Molecular Genetic Pathogenesis

The comparatively young mean age at onset of medulloblastoma in individuals with nevoid basal cell carcinoma syndrome (NBCCS) (age 2 years vs 7 years in the general population) and the loss of the normal PTCH1 allele in tumors [Cowan et al 1997] confirm PTCH1 as a tumor suppressor in medulloblastoma as well as in BCC. Inactivation of the normal allele also appears to be the mechanism responsible for jaw cysts, whereas the congenital malformations are likely to result from alterations in the concentration of the protein patched homolog 1 in the extremely dosage-sensitive hedgehog signaling pathway [Villavicencio et al 2000].

PTCH2, highly homologous to PTCH1, was mapped to chromosome 1p32.1-p32.3 [Smyth et al 1999]. Mutations were found in one simplex case (i.e., a single occurrence of the disease in a family) of medulloblastoma and one simplex case of BCC. No PTCH2 mutations were found in 11 simplex cases of NBCCS or 11 individuals with familial cases of NBCCS who did not have identifiable PTCH1 mutations.

Gene structure. PTCH1 consists of 23 exons. For a detailed summary of gene and protein information, see Table A, Gene Symbol.

Benign allelic variants. Benign variants in PTCH1 have been identified.

Pathogenic allelic variants. See Table 2.

Table 2. Frequency of Pathogenic Genetic Mechanisms

% of Individuals Affected with NBCCS 1 Type of Mutation
65%Premature termination codon (predicting a protein truncation
16%Missense
13%Splice-site
6%Exonic, multiexonic, or large-scale deletions or rearrangements

Source: literature and 395 samples from diagnostic laboratory, Birmingham Women's Hospital, UK, August 2007 (Proportions of types of mutation have remained the same over several years.)

Normal gene product. Protein patched homolog 1 is an integral membrane protein with 12 transmembrane regions, two extracellular loops, and a putative sterol-sensing domain. Protein patched homolog 1 binds the secreted factor sonic hedgehog (SHH) and functions as the SHH receptor. The protein represses the signaling activity of the co-receptor smoothened (SMOH). When in complex with SHH, protein patched homolog 1 is not a repressor, and signaling ensues. At least three forms of the protein patched homolog 1 are present in human cells [Hahn et al 1996].

Abnormal gene product. Pathogenic variants found in individuals with NBCCS and non-familial BCC include those predicted to result in a truncated protein and missense mutations.

References

Published Guidelines/Consensus Statements

  1. American Society of Clinical Oncology. Policy statement update: genetic testing for cancer susceptibility. Available online. 2003. Accessed 6-18-14.

Literature Cited

  1. Alessi SS, Sanches JA, Oliveira WR, Messina MC, Pimentel ER, Festa Neto C. Treatment of cutaneous tumors with topical 5% imiquimod cream. Clinics (Sao Paulo). 2009;64:961–6. [PMC free article: PMC2763070] [PubMed: 19841702]
  2. Amlashi SF, Riffaud L, Brassier G, Morandi X. Nevoid basal cell carcinoma syndrome: relation with desmoplastic medulloblastoma in infancy. A population-based study and review of the literature. Cancer. 2003;98:618–24. [PubMed: 12879481]
  3. Black GC, Mazerolle CJ, Wang Y, Campsall KD, Petrin D, Leonard BC, Damji KF, Evans DG, McLeod D, Wallace VA. Abnormalities of the vitreoretinal interface caused by dysregulated Hedgehog signaling during retinal development. Hum Mol Genet. 2003;12:3269–76. [PubMed: 14570707]
  4. Boutet N, Bignon YJ, Drouin-Garraud V, Sarda P, Longy M, Lacombe D, Gorry P. Spectrum of PTCH1 mutations in French patients with Gorlin syndrome. J Invest Dermatol. 2003;121:478–81. [PubMed: 12925203]
  5. Bree AF, Shah MR. BCNS Colloquium Group; Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). Am J Med Genet A. 2011;155A:2091–7. [PubMed: 21834049]
  6. Brugières L, Remenieras A, Pierron G, Varlet P, Forget S, Byrde V, Bombled J, Puget S, Caron O, Dufour C, Delattre O, Bressac-de Paillerets B, Grill J. High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age. J Clin Oncol. 2012;30:2087–93. [PubMed: 22508808]
  7. Cowan R, Hoban P, Kelsey A, Birch JM, Gattamaneni R, Evans DG. The gene for the naevoid basal cell carcinoma syndrome acts as a tumour-suppressor gene in medulloblastoma. Br J Cancer. 1997;76:141–5. [PMC free article: PMC2223943] [PubMed: 9231911]
  8. Debeer P, Devriendt K. Early recognition of basal cell naevus syndrome. Eur J Pediatr. 2005;164:123–5. [PubMed: 15717175]
  9. Evans DG, Birch JM, Orton CI. Brain tumours and the occurrence of severe invasive basal cell carcinoma in first degree relatives with Gorlin syndrome. Br J Neurosurg. 1991a;5:643–6. [PubMed: 1772613]
  10. Evans DG, Farndon PA, Burnell LD, Gattamaneni HR, Birch JM. The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma. Br J Cancer. 1991b;64:959–61. [PMC free article: PMC1977448] [PubMed: 1931625]
  11. Evans DG, Ladusans EJ, Rimmer S, Burnell LD, Thakker N, Farndon PA. Complications of the naevoid basal cell carcinoma syndrome: results of a population based study. J Med Genet. 1993;30:460–4. [PMC free article: PMC1016416] [PubMed: 8326488]
  12. Evans DGR, Ramsden RT, Shenton A, Gokhale C, Bowers NL, Huson SM, Wallace A. Mosaicism in NF2 an update of risk based on uni/bilaterality of vestibular schwannoma at presentation and sensitive mutation analysis including MLPA. J Med Genet. 2007;44:424–8. [PMC free article: PMC2598002] [PubMed: 17307835]
  13. Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson SM, Lalloo F. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A. 2010;152A:327–32. [PubMed: 20082463]
  14. Farndon PA. Gorlin (naevoid basal cell carcinoma) syndrome. In: Eeles R, Easton DF, Ponder BAJ, Eng C, eds. Genetic Predisposition to Cancer. London, UK: Hodder Arnold; 2004:193-213.
  15. Goldberg LH, Landau JM, Moody MN, Kazakevich N, Holzer AM, Myers A. Resolution of odontogenic keratocysts of the jaw in basal cell nevus syndrome with GDC-0449. Arch Dermatol. 2011;147:839–41. [PubMed: 21422324]
  16. Gorlin RJ. Nevoid basal cell carcinoma (Gorlin) syndrome. Genet Med. 2004;6:530–9. [PubMed: 15545751]
  17. Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell. 1996;85:841–51. [PubMed: 8681379]
  18. Haylett AK, Ward TH, Moore JV. DNA damage and repair in Gorlin syndrome and normal fibroblasts after aminolevulinic acid photodynamic therapy: a comet assay study. Photochem Photobiol. 2003;78:337–41. [PubMed: 14626660]
  19. Itkin A, Gilchrest BA. delta-Aminolevulinic acid and blue light photodynamic therapy for treatment of multiple basal cell carcinomas in two patients with nevoid basal cell carcinoma syndrome. Dermatol Surg. 2004;30:1054–61. [PubMed: 15209801]
  20. Jones EA, Sajid MI, Shenton A, Evans DG. Basal cell carcinomas in gorlin syndrome: a review of 202 patients. J Skin Cancer. 2011;2011:217378. [PMC free article: PMC2998699] [PubMed: 21152126]
  21. Kagy MK, Amonette R. The use of imiquimod 5% cream for the treatment of superficial basal cell carcinomas in a basal cell nevus syndrome patient. Dermatol Surg. 2000;26:577–8. [PubMed: 10848940]
  22. Kijima C, Miyashita T, Suzuki M, Oka H, Fujii K. Two cases of nevoid basal cell carcinoma syndrome associated with meningioma caused by a PTCH1 or SUFU germline mutation. Fam Cancer. 2012;11:565–70. [PubMed: 22829011]
  23. Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, Bale AE, Bale SJ. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet. 1997;69:299–308. [PubMed: 9096761]
  24. Kimonis VE, Mehta SG, Digiovanna JJ, Bale SJ, Pastakia B. Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndrome. Genet Med. 2004;6:495–502. [PubMed: 15545745]
  25. Klein RD, Dykas DJ, Bale AE. Clinical testing for the nevoid basal cell carcinoma syndrome in a DNA diagnostic laboratory. Genet Med. 2005;7:611–9. [PubMed: 16301862]
  26. Lo Muzio L, Pastorino L, Levanat S, Musani V, Situm M, Ponti G, Bianchi Scarra G. Clinical utility gene card for: Gorlin syndrome--update 2013. Eur J Hum Genet. 2013;21(10) [PMC free article: PMC3778338] [PubMed: 23361221]
  27. Loncaster J, Swindell R, Slevin F, Sheridan L, Allan D, Allan E. Efficacy of photodynamic therapy as a treatment for Gorlin syndrome-related basal cell carcinomas. Clin Oncol (R Coll Radiol). 2009;21:502–8. [PubMed: 19398312]
  28. Marks R, Gebauer K, Shumack S, Amies M, Bryden J, Fox TL, Owens ML. Imiquimod 5% cream in the treatment of superficial basal cell carcinoma: results of a multicenter 6-week dose-response trial. J Am Acad Dermatol. 2001;44:807–13. [PubMed: 11312429]
  29. Marsh A, Wicking C, Wainwright B, Chenevix-Trench G. DHPLC analysis of patients with Nevoid Basal Cell Carcinoma Syndrome reveals novel PTCH missense mutations in the sterol-sensing domain. Hum Mutat. 2005;26:283. [PubMed: 16088933]
  30. Ming JE, Kaupas ME, Roessler E, Brunner HG, Golabi M, Tekin M, Stratton RF, Sujansky E, Bale SJ, Muenke M. Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly. Hum Genet. 2002;110:297–301. [PubMed: 11941477]
  31. Mohs FE, Jones DL, Koranda FC. Microscopically controlled surgery for carcinomas in patients with nevoid basal cell carcinoma syndrome. Arch Dermatol. 1980;116:777–9. [PubMed: 7396540]
  32. Muller EA, Swaroop A, Atkin JF, Elliott AM, Chudley AE, Clark RD, Everman DB, Garner S, Hall BD, Herman GE, Kivuva E, Ramanathan S, Stevenson DA, Stockton DW, Hudgins L. Microdeletion 9q22.3 syndrome includes metopic craniosynostosis, hydrocephalus, macrosomia and developmental delay. Am J Med Genet A. 2012;158A:391–9. [PubMed: 22190277]
  33. Nagao K, Fujii K, Saito K, Sugita K, Endo M, Motojima T, Hatsuse H, Miyashita T. Entire PTCH1 deletion is a common event in point mutation-negative cases with nevoid basal cell carcinoma syndrome in Japan. Clin Genet. 2011;79:196–8. [PubMed: 21210781]
  34. Oley CA, Sharpe H, Chenevix-Trench G. Basal cell carcinomas, coarse sparse hair, and milia. Am J Med Genet. 1992;43:799–804. [PubMed: 1642265]
  35. Oseroff AR, Shieh S, Frawley NP, Cheney R, Blumenson LE, Pivnick EK, Bellnier DA. Treatment of diffuse basal cell carcinomas and basaloid follicular hamartomas in nevoid basal cell carcinoma syndrome by wide-area 5-aminolevulinic acid photodynamic therapy. Arch Dermatol. 2005;141:60–7. [PubMed: 15655143]
  36. Pereira CM, Lopes AP, Meneghini AJ, Silva AF, Botelho Tde L. Oral diffuse B-cell non-Hodgkin's lymphoma associated to Gorlin-Goltz syndrome: a case report with one year follow-up. Indian J Pathol Microbiol. 2011;54:388–90. [PubMed: 21623100]
  37. Ponti G, Pollio A, Mignogna MD, Pellacani G, Pastorino L, Bianchi-Scarrà G, Di Gregorio C, Magnoni C, Azzoni P, Greco M, Seidenari S. Unicystic ameloblastoma associated with the novel K729M PTCH1 mutation in a patient with nevoid basal cell carcinoma (Gorlin) syndrome. Cancer Genet. 2012;205:177–81. [PubMed: 22559979]
  38. Ragge NK, Salt A, Collin JR, Michalski A, Farndon PA. Gorlin syndrome: the PTCH gene links ocular developmental defects and tumour formation. Br J Ophthalmol. 2005;89:988–91. [PMC free article: PMC1772759] [PubMed: 16024850]
  39. Ratcliffe JF, Shanley S, Chenevix-Trench G. The prevalence of cervical and thoracic congenital skeletal abnormalities in basal cell naevus syndrome; a review of cervical and chest radiographs in 80 patients with BCNS. Br J Radiol. 1995;68:596–9. [PubMed: 7627481]
  40. Ribeiro LA, Murray JC, Richieri-Costa A. PTCH mutations in four Brazilian patients with holoprosencephaly and in one with holoprosencephaly-like features and normal MRI. Am J Med Genet A. 2006;140:2584–6. [PubMed: 17001668]
  41. Saran A. Basal cell carcinoma and the carcinogenic role of aberrant Hedgehog signaling. Future Oncol. 2010;6:1003–14. [PubMed: 20528237]
  42. Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366:2171–9. [PubMed: 22670903]
  43. Seracchioli R, Bagnoli A, Colombo FM, Missiroli S, Venturoli S. Conservative treatment of recurrent ovarian fibromas in a young patient affected by Gorlin syndrome. Hum Reprod. 2001;16:1261–3. [PubMed: 11387302]
  44. Shanley S, Ratcliffe J, Hockey A, Haan E, Oley C, Ravine D, Martin N, Wicking C, Chenevix-Trench G. Nevoid basal cell carcinoma syndrome: review of 118 affected individuals. Am J Med Genet. 1994;50:282–90. [PubMed: 8042673]
  45. Smyth I, Narang MA, Evans T, Heimann C, Nakamura Y, Chenevix-Trench G, Pietsch T, Wicking C, Wainwright BJ. Isolation and characterization of human patched 2 (PTCH2), a putative tumour suppressor gene in basal cell carcinoma and medulloblastoma on chromosome 1p32. Hum Mol Genet. 1999;8:291–7. [PubMed: 9931336]
  46. Stockfleth E, Ulrich C, Hauschild A, Lischner S, Meyer T, Christophers E. Successful treatment of basal cell carcinomas in a nevoid basal cell carcinoma syndrome with topical 5% imiquimod. Eur J Dermatol. 2002;12:569–72. [PubMed: 12459530]
  47. Strong LC. Genetic and environmental interactions. Cancer. 1977;40:1861–6. [PubMed: 332332]
  48. Tang JY, Mackay-Wiggan JM, Aszterbaum M, Yauch RL, Lindgren J, Chang K, Coppola C, Chanana AM, Marji J, Bickers DR, Epstein EH. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012;366:2180–8. [PubMed: 22670904]
  49. Veenstra-Knol HE, Scheewe JH, van der Vlist GJ, van Doorn ME, Ausems MG. Early recognition of basal cell naevus syndrome. Eur J Pediatr. 2005;164:126–30. [PubMed: 15717176]
  50. Villavicencio EH, Walterhouse DO, Iannaccone PM. The sonic hedgehog-patched-gli pathway in human development and disease. Am J Hum Genet. 2000;67:1047–54. [PMC free article: PMC1288546] [PubMed: 11001584]
  51. Watson J, Depasquale K, Ghaderi M, Zwillenberg S. Nevoid basal cell carcinoma syndrome and fetal rhabdomyoma: a case study. Ear Nose Throat J. 2004;83:716–8. [PubMed: 15586876]
  52. Wicking C, Shanley S, Smyth I, Gillies S, Negus K, Graham S, Suthers G, Haites N, Edwards M, Wainwright B, Chenevix-Trench G. Most germ-line mutations in the nevoid basal cell carcinoma syndrome lead to a premature termination of the PATCHED protein, and no genotype-phenotype correlations are evident. Am J Hum Genet. 1997;60:21–6. [PMC free article: PMC1712561] [PubMed: 8981943]
  53. Wilding A, Ingham SL, Lalloo F, Clancy T, Huson SM, Moran A, Evans DG. Life expectancy in hereditary cancer predisposing diseases: an observational study. J Med Genet. 2012;49:264–9. [PubMed: 22362873]

Suggested Reading

  1. Huret JL. Naevoid basal cell carcinoma syndrome (NBCS). Atlas of Genetics and Cytogenetics Oncology and Haematology. 1997. Available online. Accessed 6-18-14.
  2. Rees JL. Skin cancer (including nevoid basal cell carcinoma syndrome). In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G, eds. The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID). New York, NY: McGraw-Hill. Chap 46. Available online. 2014. Accessed 7-20-10.
  3. Zurada J, Ratner D. Diagnosis and treatment of basal cell nevus syndrome. Skinmed. 2005;4:107–10. [PubMed: 15788894]

Chapter Notes

Revision History

  • 7 March 2013 (me) Comprehensive update posted live
  • 22 July 2010 (me) Comprehensive update posted live
  • 25 January 2008 (me) Comprehensive update posted to live Web site
  • 6 October 2004 (me) Comprehensive update posted to live Web site
  • 20 June 2002 (me) Review posted to live Web site
  • 21 November 2001 (pf) Original submission
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