AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Gorlin syndrome is an autosomal dominant cancer. Patients with this rare syndrome often have several organ anomalies, many of which are subtle. Study of patients with Gorlin syndrome yields useful information about its neural development and carcinogenesis. Clinicians should be familiar with Gorlin syndrome because patients tend to develop multiple neoplasms, including basal cell carcinomas and medulloblastoma, and because patients are extremely sensitive to ionizing radiation, including sunlight.

The presence of multiple abnormalities of the skin, skeleton, and nervous system have led some to call Gorlin syndrome the fifth phakomatosis. The syndrome has also been referred to as basal cell nevus syndrome. However, the "nevi" in basal cell nevus syndrome are true basal cell carcinomas; therefore, use of this name is discouraged (Gorlin, 2004).

Pathophysiology

The genetic locus for Gorlin syndrome is on chromosome subbands and bands 9q22.3-q31, as determined with linkage analysis (Gailani, 1992). Germline mutations in the patched gene (PTCH) have been found in patients with Gorlin syndrome and are thought to cause the disorder. More than 50 germline mutations in PTCH are described. About 40% of cases of Gorlin syndrome represent new mutations.

The molecular biology of cancers in Gorlin syndrome is similar to that of retinoblastoma, the prototypical pediatric cancer syndrome, which is characterized by mutations in a recessive oncogene. Data from patients with retinoblastoma support the Knudson hypothesis, a theory of oncogenesis. This theory states that normal cells require 2 mutagenic hits (2 distinct episodes of DNA damage) to produce a cancer. Patients with retinoblastoma, Gorlin syndrome, and similar syndromes have a constitutional (germline) defect in the DNA sequence in 1 of the 2 copies of a tumor suppressor gene. A defect in 1 of the 2 gene copies is insufficient to cause a cancer. If a second DNA injury or if loss of the normal remaining allele occurs at the same locus (the second hit), the cell may become malignant.

Tumor suppressor genes act on the cellular level to suppress aberrant growth and limit the emergence of malignant clones. Loss or inactivation of such a gene can increase a person's risk for malignancies and/or overgrowth syndromes. In patients with Gorlin syndrome, the mechanism of oncogenesis mediated by ionizing irradiation is unknown. WBCs from patients with Gorlin syndrome are not exquisitely sensitive to irradiation, as is observed in cells from patients with xeroderma pigmentosum, another sun-sensitive disorder.

An interesting aspect of Gorlin syndrome is that some of the developmental defects (eg, jaw cysts) also appear to have undergone 2 genetic hits but without developing into a true malignancy. In some patients, the lining of these odontogenic keratocysts has lost the normal gene for Gorlin syndrome while retaining the mutant allele, paralleling the pathway to malignant transformation. Agaram et al (2004) found 70% of jaw cysts had loss of heterozygosity in 1 or more of the several common tumor suppressor genes. This finding may explain the behavior of the jaw cysts, which may be more like low-grade neoplasms than congenital malformations.

Study of the genetics of Gorlin syndrome has led to important basic discoveries in developmental biology. DNA analysis in patients with Gorlin syndrome has shown that the gene is homologous to a sequence in the Drosophila fruit fly called the segment polarity gene or patched gene. This patched gene is important in developmental abnormalities, growth regulation, and segmentation in Drosophila flies.

The patched gene analog in humans encodes a transmembrane protein, which binds the hedgehog protein and which represses transcription (in certain cells) of genes encoding members of the transforming growth factor (TGF)–beta and Wnt families of signaling proteins. Basal cell carcinomas in patients with Gorlin syndrome have abnormalities in the patched sequence; this observation reinforces the importance of the Gorlin mutation in oncogenesis and suggests a potential role of this gene as a tumor suppressor. DNA from sporadic basal cell carcinomas (in patients who were otherwise healthy and did not have Gorlin syndrome) also have allelic loss in the nevoid basal cell carcinoma syndrome region, with inactivating mutations of the remaining allele. This finding suggests that the gene may play a role in a final common pathway to oncogenesis in basal cell carcinomas.

Gailani et al (1992) showed that inactivation of patched gene is probably a necessary step in the development of basal cell carcinoma, even in patients without Gorlin syndrome. As many as one third of patients with medulloblastoma and Gorlin syndrome have lost the wild-type allele on chromosome arm 9q, implying that this site may code for tumor suppressor activity. Multiple defects in the Gorlin syndrome gene are reported. Wicking et al (1994) concluded that the preponderance of truncation mutations in the germ line of patients with Gorlin syndrome suggest that the developmental defects are likely a result of haploinsufficiency.

Frequency

International

Incidence of Gorlin syndrome is estimated to be 1 in 50,000-150,000 in the general population. The perceived incidence may vary by region. For example, the apparent incidence may be highest in Australia. This may be a result of demographics because a large percentage of the Australian population is made up of fair-skinned peoples transplanted from Europe to the intense solar climate in parts of Australia. People with subtle cases that may not be identified if they live in cool northern areas; similar people are likely to present to medical attention in warm southern areas.

Mortality/Morbidity

• Early death from Gorlin syndrome is rare. Important potential causes of early death include the effects of medulloblastoma, which is a malignant brain tumor of the posterior fossa that develops in 10% of patients with Gorlin syndrome.
• In rare cases, patients die from relentlessly invasive basal cell carcinomas that are treated with irradiation, which causes further damage and carcinogenesis.
• Morbidity from the complications of Gorlin syndrome can be substantial, as outlined in Physical.

Race

Gorlin syndrome has been described in Caucasians and African Americans.

Sex

This disorder is inherited in an autosomal dominant fashion and appears to occur with equal frequency in men and women.

Age

• One of the challenges of Gorlin syndrome is recognizing it (Veenstra-Knol, 2005). Although the disease is distinctive when fully expressed, many of its physical findings are absent in early childhood. Several developmental anomalies accumulate with age, with median time of diagnosis in the second or third decades of life. This variation makes definitive diagnosis in childhood difficult in many patients.
• Probably the most important reason for recognizing Gorlin syndrome is that, like other cancer syndromes, patients may develop multiple neoplasms at an early age. Basal cell carcinomas of the skin are the neoplasms most commonly observed, they occur in more than 90% of patients, and they are especially common with advancing age (>40 y).

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Patients most commonly present with either dental cysts or basal cell carcinomas in the third or fourth decade of life. Rare patients present with medulloblastoma in childhood. In a considerable number of patients, the syndrome is probably never diagnosed.

Physical

Consider a diagnosis of Gorlin syndrome in any patient who presents with basal cell carcinomas at an early age (eg, <30 y), especially if the tumors occur in the skin with minimal sun exposure (in contradistinction to typical sites, eg, tip of the nose or ear). Suspicion for Gorlin syndrome should be high if basal cell carcinomas are detected in the pediatric age range. Gorlin syndrome may never be diagnosed in a notable number of patients.

Physical findings in Gorlin syndrome are variable. Many abnormalities have been described, but the cardinal features are basal cell carcinomas (ie, nevi) at an early age. The nevi of Gorlin syndrome are typically unimpressive in appearance, measuring only a few millimeters in diameter, and they are often pigmented and pedunculated. Despite this appearance, biopsy uniformly reveals basal cell carcinoma.

Many physical findings are described in patients with Gorlin syndrome. One of the most sensitive and specific findings is the presence of palmar and plantar pits. These tiny dermal defects are readily observed with a magnifier with a tangential light source. They are highly specific for Gorlin syndrome. However, the pits are not always present in young children, and they become apparent in most patients as they age.

• Kimonis et al (1997) proposed that Gorlin syndrome can be diagnosed when 2 major or 1 major and 2 minor criteria are present.
• • Major criteria
    • Two or more basal cell carcinomas in persons younger than 20 years
    • Odontogenic keratocysts of the jaw
    • Three or more palmar or plantar pits
    • Bilamellar calcification of the falx cerebri
    • Bifid, fused, or markedly splayed ribs
    • First-degree relative with Gorlin syndrome
  • Minor criteria
    • Macrocephaly
    • Congenital malformations (eg, cleft lip or palate, frontal bossing, coarse face, hypertelorism)
    • Other skeletal abnormalities, eg, Sprengel deformity, marked pectus deformity, or syndactyly of the digits
    • Radiologic abnormalities, eg, bridging of the sella turcica, vertebral anomalies (eg, hemivertebrae, fusion or elongation of the vertebral bodies), modeling defects of the hands and feet, or flame-shaped lucencies of the hands or feet
    • Ovarian fibroma
    • Medulloblastoma
• Diagnostic criteria are not uniformly present at an early age. For example, in 1 series of patients with Gorlin syndrome (Shanley, 1994), the mean age that basal cell carcinomas appeared was 20 years. Jaw cysts were first noted at a mean age of 15 years. Similarly, palmar pits are not uniformly present at an early age. Therefore, these 3 major criteria (ie, basal cell carcinomas, jaw cysts, palmar pits) are only variably present at a young age; this variation makes definitive diagnosis difficult in many young patients.
• Although keratoses of the jaw are benign abnormalities, surgical intervention is required. Of interest, they can recur after surgery, mimicking low-grade neoplasm more than a congenital anomaly.

Causes

See Pathophysiology.

WORKUP

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• No specific laboratory studies are indicated.
• The genetic test for Gorlin syndrome is not commercially available, and it is usually unnecessary for diagnosis.

Imaging Studies

• Depending on the situation, imaging studies may include MRI of the brain, echocardiography, abdominal ultrasonography, dental radiography, and skeletal survey.
• Kimonis et al (2004) described the radiologic findings that are most helpful in diagnosing Gorlin syndrome. Because patients with Gorlin syndrome are especially sensitive to ionizing radiation, minimize the use of irradiation when possible.

Procedures

• Patients with suspected Gorlin syndrome undergo biopsy with samples obtained from several suspicious skin lesions.
• If an infratentorial mass is detected during brain MRI, it should be sampled during biopsy as well.

Histologic Findings

The histologic features of the basal cell carcinomas in Gorlin syndrome are usually identical to those observed in sporadic basal cell carcinomas. Medulloblastomas in Gorlin syndrome usually have the desmoplastic phenotype, which has been linked, in some studies, with an improved prognosis (Amlashi, 2003).

Staging

Basal cell carcinomas are not typically staged in Gorlin syndrome; they tend to be nonaggressive lesions. Some reports state that basal cell carcinomas of the scalp are more aggressive than those in other locations. The Chang staging system is used to stage medulloblastoma in Gorlin syndrome.

TREATMENT

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Patients with Gorlin syndrome can have several medical problems related to their congenital anomalies. They may need to be treated by a wide range of specialists, including dermatologists, dentists, cardiologists, oncologists, and orthopedic surgeons. Patients most commonly present to a dermatologist because of skin nodules.

Treatment of Gorlin syndrome can be difficult because of multiple and widespread basal cell carcinomas, especially in patients whose carcinomas are due to previous therapy with ionizing irradiation.

Treatment of basal cell carcinoma

Surgical excision is the typical approach to a patient with a basal cell carcinoma if the number of lesions is limited. However, in patients who present with numerous lesions, other modalities may be needed. Other treatments that may be effective and more efficient than surgical excision in patients with multiple lesions include laser ablation, photodynamic therapy, and topical chemotherapy (Oseroff, 2005).

Laser ablation is quick and efficient but can lead to scarring. In addition, the lack of surgical margins hinders the determination of whether total resection was achieved.

Photodynamic therapy can effectively treat hundreds of basal cell carcinomas simultaneously. However, it can be associated with pain, scarring, and skin burning. Patients take a prodrug administered orally, intravenously, or topically. Tumor cells preferentially take up some prodrugs. The drug is then photoactivated with a laser or UV light to form an active moiety.

Widespread basal cell carcinomas can also be treated with chemotherapy, including 5-flourouracil and/or topical tretinoin, though clinically significant local reactions can be observed with these drugs as well. Of note, the basal cell carcinomas in Gorlin syndrome only rarely become invasive. Most patients achieve good disease control without aggressive therapy.

Treatment of odontogenic keratosis

Odontogenic keratosis in the jaw may require intervention. These lesions are typically removed with surgery. However, they can recur, and several interventions may be required. This course reflects their neoplastic nature.

Treatment of medulloblastoma

Patients with Gorlin syndrome can present with medulloblastoma, a malignant tumor of the posterior fossa. For children, the median age for the diagnosis of medulloblastoma is about 5 years; the median age at presentation is about 2 years in the subgroup with medulloblastoma and Gorlin syndrome. Approximately 10% of patients with medulloblastoma who are younger than 2 years have Gorlin syndrome.

Intensive multimodality therapy is typically required to treat medulloblastoma. The best outcomes have been obtained in patients who were treated with aggressive resection, chemotherapy, and radiation therapy. Patients with Gorlin syndrome are sensitive to ionizing radiation, and therapeutic irradiation causes multiple basal cell carcinomas in these patients. In some patients, iatrogenic lesions can number in the thousands. For this reason, patients with Gorlin syndrome and medulloblastoma are best treated without standard radiation therapy.

One approach is to use a skin-sparing technique. Patients may benefit from a skin-sparing approach to radiation using nonconformal techniques. If possible, treat patients without radiation therapy or use a treatment field that only includes the posterior fossa. A nonconformal technique limits the area of skin exposed to radiation but may increase posttreatment morbidity in other ways. The advantage of skin sparing is that a reduced amount of skin is exposed to ionizing radiation; therefore, the risk of multiple radiation-induced basal cell carcinomas may be decreased. On the contrary, a nonconformal technique may increase the risk of other, well-established toxicities, such as ototoxicity and irradiation of the temporal lobes, among others. The pros and cons of these approaches must be carefully weighed.

Evidence suggests that young children with Gorlin syndrome and medulloblastoma, the population most at risk for postradiation morbidity, may have outcomes better than those of patients with sporadic medulloblastoma (Amlashi, 2003). This hypothesis arises from the observation that many patients with Gorlin syndrome and medulloblastoma have the desmoplastic subtype of medulloblastoma, which was associated with an improved prognosis compared with classic medulloblastoma in some series. Therefore, this could be one argument to limit therapy to young children with Gorlin syndrome and desmoplastic medulloblastoma.

The most important way to limit therapy is to omit or to limit the neuraxis volume irradiated. Precedence exists for the use of this approach in young children with Gorlin syndrome, some of whom have been treated with irradiation to only the posterior fossa in addition to chemotherapy, including intrathecal chemotherapy (as observed by the author). Further support derives from a study by the Pediatric Brain Tumor Consortium, in which infants with medulloblastoma but not Gorlin syndrome were treated with chemotherapy, including intrathecal chemotherapy, and an irradiation field limited to only the posterior fossa.

The important part of the treatment of children with medulloblastoma and Gorlin syndrome is the avoidance of widespread, high-dose radiation therapy.

Chemoprevention

Chemoprevention may also be used in patients with Gorlin syndrome.

Retinoids, including isotretinoin, are vitamin A analogs that may have an important role in preventing or slowing the development of cancers. Isotretinoin is effective in preventing the emergence of new basal cell carcinomas in patients with Gorlin syndrome or xeroderma pigmentosum. This property is especially important in patients at very high risk for developing multiple basal cell carcinomas, for example, those who received radiation therapy. However, isotretinoin does not appear to be useful in preventing skin cancers in healthy adults.

Oral chemoprevention is most relevant for patients with numerous tumors that cannot be treated with local measures. Some toxicity is associated with these drugs, and they are effective only for as long as they are taken. After the drugs are stopped, the cancers grow again. Whether the use of retinoids can lead to tumor regression in patients with Gorlin syndrome is unclear.

Surgical Care

• Surgical excision is the typical approach to a patient with a basal cell carcinoma. Excision is certainly feasible in patients with limited numbers of lesions. However, in patients with numerous lesions, other modalities may be needed.
• Although keratoses of the jaw are benign abnormalities, surgical intervention is required. These keratoses can recur after surgery, acting more like low-grade neoplasms than congenital anomalies.

Consultations

Patients with Gorlin syndrome can have many medical problems related to their congenital anomalies. They may require consultation with a wide range of specialists including dermatologists, dentists, cardiologists, oncologists, and orthopedic surgeons. Advise patients with Gorlin syndrome to consult a geneticist to discuss transmission of the disease and identification of other afflicted family members.

Activity

Although some patients seem to be more sensitive to sun exposure than others, all patients should avoid sun exposure to decrease the risk of basal cell carcinoma formation. However, avoiding sun exposure does not ensure that basal cell carcinomas will not develop.

MEDICATION

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Basal cell carcinomas are usually not treated medically. In Gorlin syndrome, large numbers of lesions may limit the utility of surgery alone. Although a few scattered cutaneous carcinomas can be excised, patients with hundreds or thousands of lesions need alternate therapy. Topical 5-flourouracil with or without topical tretinoin is probably the best topical option.

The use of oral isotretinoin alone is a good option for patients with a limited number of lesions but who are at high risk for developing numerous future lesions (eg, secondary to radiation therapy). In patients with numerous lesions who are at risk for developing many additional lesions, a combination of these 2 approaches can be used.

Use of retinoids in this fashion is a novel form of chemoprevention. In addition, retinoids may act in part by inducing differentiation of tissue.

Drug Category: Retinoids

Retinoids are important in the therapy of skin diseases. Retinoids affect the keratinization process. Their use as antineoplastic agents is based on an ability to maintain epithelial cell differentiation and modify cell growth and differentiation. Proposed mechanisms of action of the retinoids include the following:

• Stimulation of mitotic activity and increase in follicular cell turnover
• Corticosteroidlike mechanism (eg, anti-inflammatory)
• Affect on posttranslational glycosylation
• Disruption of the cell membrane
• Release of liposomal enzymes
• Suppression of ornithine decarboxylase (ie, DNA synthesis inhibition)
• Immunostimulation of T-killer cells
• Inhibition of polymorphonuclear (PMN) leukocyte function

Drug Category: Antineoplastic agents

Cancer chemotherapy is based on an understanding of tumoral cell growth and of how drugs affect this growth. After cells divide, they enter a period of growth (phase G1), followed by DNA synthesis (phase S). The next phase is a premitotic phase (phase G2), then finally a mitotic cell division (phase M).

Cell division rate varies for different tumors. Most common cancers grow slowly compared with normal tissues, and the rate may decrease further in large tumors. This difference allows normal cells to recover from chemotherapy more quickly than malignant cells, and this is the rationale for current cyclic dosage schedules.

Antineoplastic agents interfere with cell reproduction. Some agents are specific to the cell cycle, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not phase specific. Cellular apoptosis (ie, programmed cell death) is also a potential mechanism of many antineoplastic agents.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Deterrence/Prevention

• Patients with Gorlin syndrome are extremely sensitive to ionizing radiation.
• Excessive sun exposure is a risk factor for skin cancers of many types, including basal cell carcinomas, even in the general population. However, the risk is higher in patients with Gorlin syndrome than in others.
• Virtually every patient with Gorlin syndrome eventually develops basal cell carcinomas, regardless of their sun exposure. Nevertheless, counsel patients to avoid sun exposure.
• Minimize the use of radiographic irradiation and irradiation to treat cancer.

Complications

• See Physical.

Patient Education

• Counsel patients to avoid sun exposure and radiographic irradiation.
• Advise patients to consult a geneticist to discuss transmission of the disease and identification of other affected family members.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Special Concerns

• Patients with Gorlin syndrome are extremely sensitive to ionizing radiation, and the use of therapeutic irradiation causes multiple basal cell carcinomas in patients with Gorlin syndrome.
• In some patients, iatrogenic lesions can number in the thousands. For this reason, nonstandard treatments should be considered for children with Gorlin syndrome and medulloblastoma, including limited radiation fields; skin-sparing, nonconformal techniques; and treatments that exclude radiation therapy, such as high-dose chemotherapy with peripheral stem cell rescue.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Agaram NP, Collins BM, Barnes L, et al. Molecular analysis to demonstrate that odontogenic keratocysts are neoplastic. Arch Pathol Lab Med. Mar 2004;128(3):313-7. [Medline].
• 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. Aug 1 2003;98(3):618-24. [Medline].
• Bale AE. The nevoid basal cell carcinoma syndrome: genetics and mechanism of carcinogenesis. Cancer Invest. 1997;15(2):180-6. [Medline].
• Evans DG, Farndon PA, Burnell LD, et al. The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma. Br J Cancer. Nov 1991;64(5):959-61. [Medline].
• Gailani MR, Bale SJ, Leffell DJ, et al. Developmental defects in Gorlin syndrome related to a putative tumor suppressor gene on chromosome 9. Cell. Apr 3 1992;69(1):111-7. [Medline].
• Gorlin RJ. Nevoid basal cell carcinoma syndrome. Dermatol Clin. Jan 1995;13(1):113-25. [Medline].
• Gorlin RJ. Nevoid basal cell carcinoma (Gorlin) syndrome. Genet Med. Nov-Dec 2004;6(6):530-9. [Medline].
• Hahn H, Wicking C, Zaphiropoulous PG, et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell. Jun 14 1996;85(6):841-51. [Medline].
• Kimonis VE, Goldstein AM, Pastakia B, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet. Mar 31 1997;69(3):299-308. [Medline].
• Kimonis VE, Mehta SG, Digiovanna JJ, et al. Radiological features in 82 patients with nevoid basal cell carcinoma (NBCC or Gorlin) syndrome. Genet Med. Nov-Dec 2004;6(6):495-502. [Medline].
• Levanat S, Gorlin RJ, Fallet S, et al. A two-hit model for developmental defects in Gorlin syndrome. Nat Genet. Jan 1996;12(1):85-7. [Medline].
• Oseroff AR, Shieh S, Frawley NP, et al. 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. Jan 2005;141(1):60-7. [Medline].
• Shanley S, Ratcliffe J, Hockey A, et al. Nevoid basal cell carcinoma syndrome: review of 118 affected individuals. Am J Med Genet. Apr 15 1994;50(3):282-90. [Medline].
• Veenstra-Knol HE, Scheewe JH, van der Vlist GJ, et al. Early recognition of basal cell naevus syndrome. Eur J Pediatr. Mar 2005;164(3):126-30. [Medline].
• Walter AW, Pivnick EK, Bale AE, Kun LE. Complications of the nevoid basal cell carcinoma syndrome: a case report. J Pediatr Hematol Oncol. May-Jun 1997;19(3):258-62. [Medline].
• Walter AW, Heideman R, Kun LE. The treatment of medulloblastoma in children with Gorlin syndrome without the use of standard radiation therapy [abstract]. Presented at: Meeting of Society of Neuro-Oncology;. 1999.
• Wicking C, Berkman J, Wainwright B, Chenevix-Trench G. Fine genetic mapping of the gene for nevoid basal cell carcinoma syndrome. Genomics. Aug 1994;22(3):505-11. [Medline].

Article Last Updated: Dec 20, 2006