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Disease Profile

Nevoid basal cell carcinoma syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Adolescent

ICD-10

C44.9

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Gorlin-Goltz Syndrome; Basal Cell Nevus Syndrome; Multiple Basal Cell Nevi, Odontogenic Keratocysts, And Skeletal Anomalies;

Categories

Congenital and Genetic Diseases; Eye diseases; Nervous System Diseases;

Summary

Nevoid basal cell carcinoma syndrome (NBCCS) leads to the growth of non-cancerous and cancerous tumors. The symptoms include basal cell cancers, jaw cysts, skin pits on the hands and feet, and abnormal deposits of calcium in the brain. Other symptoms may include bone abnormalities of the spine, ribs, or skull, and a large head. Some of the signs and symptoms of NBCCS are present at birth. There is an increased risk for a type of brain tumor (medulloblastoma) in childhood. Jaw cysts and basal cell cancers typically appear by adulthood. NBCCS occurs when the PTCH1, PTCH2or the SUFU gene is not working correctly. It is inherited in an autosomal dominant manner. NBCCS is diagnosed based on clinical examination for specific features and genetic testing. Treatment is aimed at addressing the symptoms and associated cancers.[1][2][3]

Symptoms

The following list includes the most common signs and symptoms in people with nevoid basal cell carcinoma syndrome (NBCCS). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms may include:[1][4][5]

  • Abnormal deposits of calcium in the brain (cerebral calcification)
  • Skeletal abnormalities (bifid ribs, wedge-shaped vertebrae)
  • Skin pits on the hands and feet (palmar and plantar pits)
  • Large head size (macrocephaly)
  • Medulloblastoma (childhood brain tumor)
  • Multiple jaw cysts (odontogenic keratocysts)
  • Basal cell carcinoma
  • Abnormal or excessive tissue growth
  • Noncancerous tumors of the heart
  • Noncancerous tumors of the ovary

The first signs of NBCCS may be a large head and skeletal abnormalities. Skin pits and jaw tumors may develop in late childhood. By adulthood, basal cell cancers and other noncancerous tumors may appear. People with NBCCS are at increased risk to develop specific types of cancerous and noncancerous tumors.[1][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Melanocytic nevus
Beauty mark
0000995
Neoplasm
0002664
Palmar pits
0010610
Plantar pits
0010612
30%-79% of people have these symptoms
Abnormality of the neck
0000464
Brachydactyly
Short fingers or toes
0001156
Scoliosis
0002650
Vertebral fusion
Spinal fusion
0002948
Vertebral wedging
Wedge-shaped vertebrae
0008422
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
5%-29% of people have these symptoms
Abnormality of the sense of smell
Abnormal sense of smell
Smell defect

[ more ]

0004408
Arachnodactyly
Long slender fingers
Spider fingers

[ more ]

0001166
Brachycephaly
Short and broad skull
0000248
Carious teeth
Dental cavities
Tooth cavities
Tooth decay

[ more ]

0000670
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Frontal bossing
0002007
Glaucoma
0000501
Hemivertebrae
Missing part of vertebrae
0002937
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypogonadotropic hypogonadism
0000044
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Iris coloboma
Cat eye
0000612
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw

[ more ]

0000303
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Telecanthus
Corners of eye widely separated
0000506
Percent of people who have these symptoms is not available through HPO
Abnormal sternum morphology
Abnormality of the sternum
Sternal anomalies

[ more ]

0000766
Autosomal dominant inheritance
0000006
Basal cell carcinoma
0002671
Bifid ribs
Cleft ribs
Split ribs

[ more ]

0000892
Bridged sella turcica
0005449
Broad face
Increased breadth of face
Increased width of face
Wide face

[ more ]

0000283
Calcification of falx cerebri
0005462
Cardiac fibroma
0010617
Cardiac rhabdomyoma
0009729
Cleft palate
Cleft roof of mouth
0000175
Cleft upper lip
Harelip
0000204
Coarse facial features
Coarse facial appearance
0000280
Down-sloping shoulders
Rounded shoulders
Rounded, sloping shoulders
Sloping shoulders

[ more ]

0200021
Hamartomatous stomach polyps
0004795
Irregular ossification of hand bones
0004280
Kyphoscoliosis
0002751
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Medulloblastoma
0002885
Microphthalmia
Abnormally small eyeball
0000568
Milia
Milk spot
0001056
Motor delay
0001270
Odontogenic keratocysts of the jaw
0010603
Orbital cyst
Cyst of eye socket
0001144
Ovarian carcinoma
0025318
Ovarian fibroma
00

Cause

Nevoid basal cell carcinoma syndrome occurs when the PTCH1, SUFU, or PTCH2 gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[1][3]

Diagnosis

Nevoid basal cell carcinoma syndrome (NBCCS) is diagnosed based on a clinical exam looking for a specific set of signs and symptoms.[6][7]. Genetic testing can be done to help with the diagnosis.

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    Treatment of nevoid basal cell carcinoma syndrome (NBCCS) is aimed at managing the symptoms and associated cancers. Basal cell cancer can be treated with chemotherapy, surgery, and other types of therapy.[1][3]

    Specialists who may be involved in the care of someone with NBCCS include:

    • Cardiologist
    • Dermatologist
    • Medical geneticist
    • Ophthalmologist
    • Oncologist

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Cancer.net, a resource from the American Society of Clinical Oncology, provides information about this condition.
        • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference (GHR) contains information on Nevoid basal cell carcinoma syndrome. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Nevoid basal cell carcinoma syndrome. Click on the link to view a sample search on this topic.

            Selected Full-Text Journal Articles

            • The Orphanet Journal of Rare Diseases has published an article with information on this condition. This journal is affiliated with the Orphanet reference portal for information on rare diseases and orphan drugs.

              References

              1. Bresler SC, Padwa BL, Granter SR. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome). Head Neck Pathol. Jun 2016; 10(2):119-24. https://www.ncbi.nlm.nih.gov/pubmed/26971503.
              2. Fujii K, Miyashita T. Gorlin syndrome (nevoid basal cell carcinoma syndrome): Update and literature review. Pediatr Int. Oct 2014; 56(5):667-74. https://www.ncbi.nlm.nih.gov/pubmed/25131638.
              3. Palacios-Álvarez I, González-Sarmiento R, Fernández-López E. Gorlin Syndrome. Síndrome de Gorlin. Actas Dermosifiliogr. 2018; 109(3):207-217. https://pubmed.ncbi.nlm.nih.gov/29373110.
              4. Evans DG, Farndon PA. Nevoid Basal Cell Carcinoma Syndrome. GeneReviews. Updated March 29, 2018; https://www.ncbi.nlm.nih.gov/books/NBK1151/.
              5. Chen JJ, Sartori J, Aakalu VK, Setabutr P. Review of ocular manifestations of nevoid basal cell carcinoma syndrome: What an ophthalmologist needs to know. Middle East Afr J Ophthalmol. OctDec 2015; 22(4):421-7. https://www.ncbi.nlm.nih.gov/pubmed/26692711.
              6. Kimonis VE, Goldstein AM, Pastakia B, et al.. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 1997;69:299–308. 1997; 69:299-308. https://pubmed.ncbi.nlm.nih.gov/9096761.
              7. 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; 30:460-464. https://pubmed.ncbi.nlm.nih.gov/8326488.
              8. Castro-Mujica MDC, Barletta-Carrillo C, Poterico JA, Acosta M, Valer J, Cruz M. Síndrome de carcinoma de células basales nevoides (Síndrome Gorlin): reporte de dos casos y revisión de la literatura [Nevoid basal-cell carcinoma syndrome (Gorlin Syndrome): report of two cases and review of the literature]. Rev Peru Med Exp Salud Publica. 2017; 34(4):744-750. https://pubmed.ncbi.nlm.nih.gov/29364426.

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