eMedicine Specialties > Pediatrics: General Medicine > Oncology

Gorlin Syndrome

Updated: Mar 23, 2009

Introduction

Background

Gorlin syndrome (basal cell nevus syndrome or nevoid basal cell carcinoma syndrome) is a rare, autosomal dominant cancer syndrome.¹ Patients with this syndrome often have anomalies of multiple organs, many of which are subtle. Study of patients with this rare but important syndrome has yielded important information about neurodevelopment and carcinogenesis.

Clinicians should be familiar with Gorlin syndrome because of the propensity of these patients to develop multiple neoplasms, including basal cell carcinomas and medulloblastoma, and because of the their extreme sensitivity 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 term nevus, as in basal cell nevus syndrome, is an archaic term referring to any circumscribed lesion believed to arise under genetic influence. However, the nevi in the basal cell nevus syndrome are true basal cell carcinomas.^2,3

Multiple small papules on the neck and upper trunk in a 10-year-old patient. Biopsy confirmed basal cell carcinoma.

Pathophysiology

The genetic locus for Gorlin syndrome is 9q22.3-q31, as determined with linkage analysis.^4,5 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.^6,7

The molecular biology of cancers in Gorlin syndrome is similar to that of patients with inherited mutations in the Rb, the retinoblastoma gene. Studies of patients with retinoblastoma have provided clinical evidence supporting the Knudson hypothesis, a theory of oncogenesis that states that normal cells require at least 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 gene copies.

The presence of a defect in 1 of the 2 gene copies is not sufficient to cause a cancer. If a second DNA injury, or loss of the normal remaining allele, occurs at the same gene (the second hit), the cell may become malignant. These tumor suppressor genes act normally by suppressing growth and limiting the emergence of malignant clones. Loss or inactivation of such a gene can lead to an increased risk for malignancies and/or overgrowth syndromes such as Gorlin syndrome.⁸

The mechanism of oncogenesis mediated by ionizing irradiation in patients with Gorlin syndrome is unknown. WBCs from patients with Gorlin syndrome are not exquisitely sensitive to irradiation as are cells from patients with another sun-sensitive disorder, xeroderma pigmentosum.

An important and interesting aspect of the study of Gorlin syndrome is that some of the developmental defects (such as jaw cysts) also appear to have undergone a “transformation” following 2 hits, without developing into a malignancy. In some patients, cells comprising the lining of the jaw cysts have lost the normal Gorlin syndrome gene while retaining the mutant allele. This may explain the behavior of the jaw cysts, which may behave more like low-grade neoplasms than congenital malformations.^9,10,11

Study of the genetics of Gorlin syndrome has led to important basic discoveries in developmental biology. DNA analysis from patients with Gorlin syndrome led to the realization that the genetic defect that causes Gorlin syndrome is homologous to a sequence in the fruit fly Drosophila called the segment polarity gene (PTCH). The PTCH gene is known to be important in developmental abnormalities, growth regulation, and segmentation in Drosophila. The PTCH gene analogue in humans codes for a transmembrane protein, which represses transcription of genes encoding members of the tumor growth factor (TGF) beta and WNT families of signaling proteins.

Basal cell carcinomas from patients with Gorlin syndrome have abnormalities of the PTCH sequence, reinforcing the importance of the Gorlin mutation in oncogenesis and suggesting a potential role of this gene as a tumor suppressor gene. DNA from sporadic basal cell carcinomas (ie, from tumors in patients who were otherwise healthy and who did not have Gorlin syndrome) also had allelic loss in the nevoid basal cell carcinoma syndrome region with inactivating mutations of the remaining allele, suggesting that the gene may play a role in a final common pathway to oncogenesis in basal cell carcinomas.

Gailani et al showed that inactivation of patched is probably a necessary step in basal cell carcinoma development, even in patients without the Gorlin syndrome.⁴ As many as one third of patients with medulloblastoma and Gorlin syndrome have lost the wild type allele on chromosome 9q, implying that this site may code for tumor suppressor activity.

The exact genetic defects in patients with Gorlin syndrome are multiple. One group identified 28 mutations distributed throughout the entire gene. They concluded that the preponderance of truncation mutations in the germ line of patients with Gorlin syndrome suggested that the developmental defects are likely due to haploinsufficiency.⁷

Frequency

International

Incidence of Gorlin syndrome is estimated to be 1 case per 50,000-150,000 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.

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 progressively 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 whites and in blacks.

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 its presence. Although quite distinctive when fully expressed, many of the physical findings are absent in early childhood. Several of the developmental anomalies accumulate with age with median time of diagnosis in the second or third decades. This makes definitive diagnosis in childhood difficult in many cases. The most important reason for recognizing Gorlin syndrome is, as with other cancer syndromes, patients can develop multiple neoplasms at an early age. The most common neoplasms seen are basal cell carcinomas of the skin, occurring in more than 90% of patients, especially with advancing age (>40 y).

Clinical

History

Patients with Gorlin syndrome 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

Numerous anomalies have been described in patients with Gorlin syndrome. These include abnormalities of the skin, head and neck, spine and bony skeleton, genitourinary system, CNS, heart, and ovaries. The most common abnormalities include calcification of the cerebral falx, distinctive pits of the palms and soles, macrocephaly, odontogenic keratocysts of the jaw,¹² one or more basal cell carcinomas (especially at a young age), rib abnormalities, and having a first degree relative with Gorlin syndrome. Less common findings include thoracic or cervical vertebral anomalies, short fourth metacarpals, pectus excavatum or pectus carinatum, cleft lip or palate,¹³ moderate or severe hypertelorism, Sprengel deformity, ovarian fibroma, or medulloblastoma. Kimonis has proposed that the diagnosis of Gorlin syndrome can be made in the presence of 2 major or 1 majorand2minorcriteriaasdiscussed below.^14,15

The diagnostic criteria may not all be present at an early age. For example, in one series of patients with Gorlin syndrome described by Shanley et al.¹⁶ The mean age of onset of basal cell carcinomas was 20 years. In this same series, 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 are only variably present at a young age, making definitive diagnosis difficult in many young patients.

Kimonis et al proposed that Gorlin syndrome can be diagnosed when 2 major or 1 major and 2 minor criteria are present.¹⁴

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

The nevi in the basal cell nevus syndrome are true basal cell carcinomas. Patients may present with multiple fleshy pigmented or nonpigmented nevi that may appear to be typical moles. However, biopsies of these lesions uniformly result in the diagnosis of basal cell carcinoma. The pits of the palms and soles are tiny epidermal defects in keratin production. Although these are often not present in young children, they are highly specific to Gorlin syndrome. The keratoses of the jaw, although benign abnormalities, require surgical intervention. They can also recur after surgery, mimicking more a low-grade neoplasm than a congenital anomaly.

Causes

See Pathophysiology.

Workup

Laboratory Studies

No specific laboratory studies are indicated.
The genetic test for Gorlin syndrome is commercially available.

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.¹⁷ Because patients with Gorlin syndrome are especially sensitive to ionizing radiation, the use of irradiation should be minimized.

Procedures

Patients with suspected Gorlin syndrome may need a biopsy of suspicious skin lesions.
If an infratentorial mass is detected on brain MRI, a craniotomy should be performed.

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 a desmoplastic histology, which has been linked to an improved prognosis in some studies.¹⁸

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 medulloblastomas in general, including those found in Gorlin syndrome.

Treatment

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, some patients with Gorlin syndrome can be difficult to manage because of multiple and widespread basal cell carcinomas. This is especially the case in patients whose carcinomas are a result of prior therapy with ionizing irradiation.¹⁹ The typical approach to a patient with a basal cell carcinoma is surgical excision. This is certainly feasible in patients with Gorlin syndrome who have a limited numbers of lesions. 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. Laser ablation is quick and efficient but can lead to scarring. In addition, no surgical margins allow a determination if a total resection was achieved. Photodynamic therapy is effective in treating large numbers of basal cell carcinomas.²⁰ Patients are treated with a prodrug administered intravenously, orally, or topically. Some prodrugs are preferentially taken up by tumor cells. The drug is then photoactivated by laser or UV light, resulting in formation of an active moiety. This therapy can simultaneously treat hundreds of lesions. However, it can be associated with pain, scarring, and skin burning.

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

Treatment of odontogenic keratosis

Odontogenic keratosis in the jaw may require surgical removal. However, they can recur after surgery and may require additional surgical procedures.

Treatment of medulloblastoma

Patients with Gorlin syndrome can present with medulloblastoma, a malignant tumor of the posterior fossa. The median age at diagnosis for a child with 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.²¹

Treatment for medulloblastoma typically requires intensive, multimodality therapy. The best outcomes have been obtained in patients who have been treated with aggressive resection, chemotherapy, and radiation therapy. Patients with Gorlin syndrome are very sensitive to ionizing radiation, and the use of therapeutic irradiation is known to cause multiple basal cell carcinomas in patients with Gorlin syndrome. In some patients, iatrogenic lesions can number in the thousands. For this reason, patients with Gorlin syndrome and medulloblastoma may be better served by treating without the use of standard radiation therapy.

Standard radiation therapy includes craniospinal irradiation, typically to a dose of 24 Gy to the brain and spine in average-risk children older than 3 years. A dose of 36 Gy is often used if metastatic disease is present at diagnosis. However, patients with Gorlin syndrome do not normally present with disseminated disease; thus, patients with Gorlin syndrome are rarely treated with a dose of 36 Gy or more. Considering nonstandard dose reductions in the craniospinal dose because of the increased risk of second malignant neoplasms following radiation therapy is reasonable.

Alternative treatment options include using a lower dose of craniospinal irradiation (eg, 18 Gy), considering protons instead of photons to decrease the body mass and skin surface area exposed to ionizing irradiation, treating with high-dose chemotherapy with reduced dose or no craniospinal irradiation, limiting radiation therapy to a posterior fossa boost only, and using intrathecal chemotherapy to reduce or replace craniospinal irradiation.

Patients may also benefit from a skin-sparing approach to radiation therapy. Planning the craniospinal and posterior fossa fields using nonconformal techniques minimizes the surface area of skin exposed to irradiation and, hopefully, minimizes the number of radiation-induced second malignant neoplasms.²² These alternative approaches may be justified because anecdotal evidence suggests that medulloblastoma in Gorlin syndrome is a less aggressive subtype.

The important part of the treatment of the child with a medulloblastoma and Gorlin syndrome is the avoidance of wide-field, high-dose radiation therapy, including craniospinal irradiation. Radiation therapy has been shown to be extremely carcinogenic in patients with Gorlin syndrome. Following therapeutic doses of radiation therapy, patients may develop hundreds or thousands of basal cell carcinomas in the radiation fields. Therefore, ideally the treatment of medulloblastoma in patients with Gorlin syndrome should be using little or no radiation therapy. One approach is to use a skin-sparing technique. The use of intrathecal chemotherapy may have a role in the treatment of medulloblastoma in Gorlin syndrome as a way to minimize or eliminate the use of radiation therapy.²²

Chemoprevention

An important issue for in patients with Gorlin syndrome is the issue of chemoprevention. The retinoids, including isotretinoin, are vitamin A analogues that may have an important role in preventing or slowing the development of cancers. Isotretinoin has been shown to be very effective in preventing the emergence of new basal cell carcinomas in patients with Gorlin syndrome and xeroderma pigmentosum. Unfortunately, isotretinoin does not appear to be useful in preventing skin cancers in normal adults. The use of 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; once stopped, the cancers grow again. Whether the retinoids can cause tumor regression in patients with Gorlin syndrome is unclear.

Although the role of retinoids is limited in patients with sporadic basal cell carcinomas not related to Gorlin syndrome, the retinoids (especially isotretinoin) have been shown to play an important role in limiting development of new neoplasm. Whether the use of oral isotretinoin can cause regression of existing neoplasms is unclear; however, in patients who are at risk for developing multiple, new basal cell carcinomas, the use of oral isotretinoin can help prevent the emergence of new tumors, especially following therapeutic radiation. However, this drug is associated with moderate systemic toxicity, and, in some patients, these side effects are not tolerable.

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. 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

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.

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

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

Tretinoin (Retin-A, Avita)

Naturally occurring stereoisomer of retinoic acid. Primarily used to treat acne vulgaris and photodamaged skin.

Dosing

Adult

Variable; typical regimen is 0.025% cream applied daily

Pediatric

Little information available on topical use in children; some reports describe use of 0.1% cream with or without occlusion once daily

Interactions

Toxicity increases with coadministration of benzoyl peroxide, salicylic acid, and resorcinol; avoid topical sulfur, resorcinol, salicylic acid, other keratolytics, abrasives, astringents, spices, and lime

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Pregnancy category B for topical use; photosensitivity may occur with excessive sunlight exposure; caution in eczema; do not apply to mucous membranes, mouth, or angles of nose

Isotretinoin (Accutane)

13-Cis -retinoic acid. Synthetic retinoid with less toxicity and higher activity than tretinoin. Typically used to treat severe cystic acne. Also used to treat children with metastatic neuroblastoma. Teratogen.

Dosing

Adult

Basal cell carcinoma: 1.5-8.2 mg/kg/d PO divided bid pc; mean dosage 4.6 mg/kg/d

Pediatric

Chemoprevention: Not established; limited data suggest 2 mg/kg/d PO divided bid pc

Interactions

Toxicity may occur with coadministration of vitamin A; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; may reduce plasma levels of carbamazepine

Contraindications

Documented hypersensitivity; pregnancy

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

May decrease night vision; inflammatory bowel disease may occur; may be associated with hepatitis; occasional exaggerated healing response of acne lesions (excessive granulation with crusting) may occur; patients with diabetes may have problems in controlling blood sugar during therapy; caution with hypertriglyceridemia; avoid exposure to UV light or sunlight until tolerance achieved; discontinue if rectal bleeding, abdominal pain, or severe diarrhea occur; mood swings or depression may occur; caution in history of depression

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.

5-Flourouracil (Efudex, Fluoroplex)

Antimetabolite. Often used to treat breast, colon, stomach, and pancreatic cancers. Topical solutions used for acne vulgaris and basal cell carcinomas.

Dosing

Adult

5% cream or lotion applied topically bid for basal cell carcinomas with or without occlusion

Pediatric

Administer as in adults

Interactions

None reported for the topical form

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Pregnancy category X for topical administration; wash hands after application; avoid contact with mucous membranes; inflammatory reactions may occur with use of occlusive dressings; porous gauze dressing may be applied for cosmetic reasons without increasing reaction; expect inflammatory reaction with crusting

Follow-up

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 diagnostic radiography and radiation therapy 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

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.

Multimedia

Media file 1: Multiple small papules on the neck and upper trunk in a 10-year-old patient. Biopsy confirmed basal cell carcinoma.

References

Lo Muzio L. Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis. Nov 25 2008;3:32. [Medline].
Gorlin RJ. Nevoid basal cell carcinoma (Gorlin) syndrome. Genet Med. Nov-Dec 2004;6(6):530-9. [Medline].
Gorlin RJ. Nevoid basal cell carcinoma syndrome. Dermatol Clin. Jan 1995;13(1):113-25. [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].
Bale AE. The nevoid basal cell carcinoma syndrome: genetics and mechanism of carcinogenesis. Cancer Invest. 1997;15(2):180-6. [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].
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].
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(2):141-5. [Medline].
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].
Gu XM, Zhao HS, Sun LS, Li TJ. PTCH mutations in sporadic and Gorlin-syndrome-related odontogenic keratocysts. J Dent Res. Sep 2006;85(9):859-63. [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].
Gonzalez-Alva P, Tanaka A, Oku Y, et al. Keratocystic odontogenic tumor: a retrospective study of 183 cases. J Oral Sci. Jun 2008;50(2):205-12. [Medline].
Mansilla MA, Cooper ME, Goldstein T, et al. Contributions of PTCH gene variants to isolated cleft lip and palate. Cleft Palate Craniofac J. Jan 2006;43(1):21-9. [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].
Friedrich RE. Diagnosis and treatment of patients with nevoid basal cell carcinoma syndrome [Gorlin-Goltz syndrome (GGS)]. Anticancer Res. Jul-Aug 2007;27(4A):1783-7. [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].
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].
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].
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].
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].
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].
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.
de Ravel TJ, Ameye L, Ballon K, Borghgraef M, Vermeesch JR, Devriendt K. Early detection of chromosome 9q22.32q31.1 microdeletion and the nevoid basal cell carcinoma syndrome. Eur J Med Genet. Feb 21 2009;[Medline].

Keywords

Gorlin syndrome, Gorlin's syndrome, basal cell nevus syndrome, nevoid basal cell carcinoma syndrome, NBCCS, basal cell carcinoma, medulloblastoma, fifth phakomatosis, nevi, patched gene, PTCH, retinoblastoma, treatment, diagnosis, cancer, cleft lip and palate, macrocephaly, rib abnormalities, pectus excavatum, pectus carinatum, ovarian fibroma, Sprengel deformity, syndactyly of the digits

Contributor Information and Disclosures

Author

Andrew W Walter, MS, MD, Associate Professor of Pediatrics, Department of Pediatrics, Division of Hematology/Oncology, Jefferson Medical College; Director of Pediatric Neuro-oncology, AI duPont Hospital for Children
Andrew W Walter, MS, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Stephan A Grupp, MD, PhD, Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania
Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Timothy P Cripe, MD, PhD, Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center
Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Department of Oncology, Division of Pediatric Oncology, Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Further Reading