{{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox medical condition (new) | image = Nevoid Basal Cell Carcinoma Syndrome 4.jpg | caption = Adult patient with NBCCS | synonyms = '''Basal-cell nevus syndrome''', '''Multiple basal-cell carcinoma syndrome''', '''Gorlin syndrome''', and '''Gorlin–Goltz syndrome''' | field = | symptoms = | complications = | onset = | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = | frequency = | deaths = }} '''Nevoid basal-cell carcinoma syndrome''' ('''NBCCS''') is a rare inherited medical condition involving defects within multiple body systems such as the [[Human skin|skin]], [[nervous system]], [[Human eyes|eyes]], [[endocrine system]], and [[bone]]s.<ref name=Kimonis_1997>{{cite journal | vauthors = Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, Bale AE, Bale SJ | title = Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome | journal = American Journal of Medical Genetics | volume = 69 | issue = 3 | pages = 299–308 | date = March 1997 | pmid = 9096761 | doi = 10.1002/(SICI)1096-8628(19970331)69:3<299::AID-AJMG16>3.0.CO;2-M | url = https://zenodo.org/record/1235524 }}</ref> People with NBCCS are prone to developing various cancers, including a common and usually non-life-threatening form of non-[[melanoma]] [[skin cancer]] called [[basal-cell carcinoma]]s (BCCs).<ref name="Spiker_2024">{{cite book | vauthors = Spiker AM, Troxell T, Ramsey ML | chapter = Gorlin Syndrome |date=2024 | title = StatPearls | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK430921/ |access-date=2024-04-11 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=28613671 }}</ref> Only about 10% of people with the condition do not develop BCCs; the vast majority of patients develop numerous BCCs.<ref name="Spiker_2024" />
''Gorlin syndrome'' refers to the American oral pathologist and human geneticist [[Robert J. Gorlin]] (1923–2006).<ref>{{cite book | vauthors = Burgdorf W | chapter = Robert J. Gorlin (1923 – 2006). | veditors = Löser C, Plewig G | title = Pantheon der Dermatologie. | location = Heidelberg | publisher = Springer | date = 2008 | pages = 362–366 }}</ref> The American dermatologist Robert W. Goltz (1923–2014)<ref name="pmid25349877">{{cite journal | vauthors = Burgdorf WH, Padilla RS, Hordinsky M | title = In memoriam: Robert W. Goltz (1923-2014) | journal = Journal of the American Academy of Dermatology | volume = 71 | issue = 4 | pages = e163–5 | date = October 2014 | pmid = 25349877 | doi = 10.1016/j.jaad.2014.04.057 }}</ref> was his co-author, which is the basis for the term 'Gorlin-Goltz syndrome'.
First described in 1960 by Gorlin and Goltz,<ref name=Gorlin_1960>{{cite journal | vauthors = Gorlin RJ, Goltz RW | title = Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib. A syndrome | journal = The New England Journal of Medicine | volume = 262 | issue = 18 | pages = 908–912 | date = May 1960 | pmid = 13851319 | doi = 10.1056/NEJM196005052621803 }}</ref> NBCCS is an [[autosomal dominant]] condition that can cause unusual facial appearances and a predisposition for basal-cell carcinoma, a type of skin cancer which rarely spreads to other parts of the body. The prevalence is reported to be 1 case per 56,000–164,000 population. Recent work in [[molecular genetics]] has shown NBCCS to be caused by mutations in the ''PTCH'' ([[PTCH1|Patched]]) gene found on [[chromosome]] arm [[Chromosome 9 (human)|9q]]<ref name=Johnson_1996>{{cite journal | vauthors = Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH, Scott MP | title = Human homolog of patched, a candidate gene for the basal cell nevus syndrome | journal = Science | volume = 272 | issue = 5268 | pages = 1668–1671 | date = June 1996 | pmid = 8658145 | doi = 10.1126/science.272.5268.1668 | s2cid = 9160210 | bibcode = 1996Sci...272.1668J }}</ref> or the ''[[SUFU]]'' gene on chromosome arm [[Chromosome 10|10q]],<ref name="Spiker_2024" /> though some patients do not have either known mutation. ''PTCH'' is important in regulating cell division and growth; thus, mutations in this gene can impact tumor growth.<ref name="Spiker_2024" /> Children who inherit defective genes from either parent will also develop the disorder.<ref name="Verkouteren_2022">{{cite journal | vauthors = Verkouteren BJ, Cosgun B, Reinders MG, Kessler PA, Vermeulen RJ, Klaassens M, Lambrechts S, van Rheenen JR, van Geel M, Vreeburg M, Mosterd K | title = A guideline for the clinical management of basal cell naevus syndrome (Gorlin-Goltz syndrome) | journal = The British Journal of Dermatology | volume = 186 | issue = 2 | pages = 215–226 | date = February 2022 | pmid = 34375441 | pmc = 9298899 | doi = 10.1111/bjd.20700 }}</ref>
==Signs and symptoms== Some or all of the following may be seen in someone with Gorlin syndrome:<ref name="Verkouteren_2022" /> # Multiple basal-cell carcinomas of the skin, most commonly on the face, hands or neck.<ref name="Spadari_2022">{{cite journal | vauthors = Spadari F, Pulicari F, Pellegrini M, Scribante A, Garagiola U | title = Multidisciplinary approach to Gorlin-Goltz syndrome: from diagnosis to surgical treatment of jawbones | journal = Maxillofacial Plastic and Reconstructive Surgery | volume = 44 | issue = 1 | pages = 25 | date = July 2022 | pmid = 35843976 | pmc = 9288940 | doi = 10.1186/s40902-022-00355-5 | doi-access = free }}</ref> # [[Odontogenic keratocyst]]: a benign tumor of the jawbone.<ref name="Spadari_2022" /> Seen in 75% of patients and is the most common finding. Multiple lesions are usually found in the mandible. They occur at a young age (19 years average). # Pits on the soles of the feet and palms of their hands.<ref name="Spadari_2022" /> # Rib and vertebrae anomalies # Intracranial calcification # Skeletal abnormalities: [[bifid rib]]s, [[kyphoscoliosis]], early calcification of [[falx cerebri]] (diagnosed with AP radiograph) # Distinct faces: [[Frontal bossing|Frontal]] and temporoparietal bossing, [[hypertelorism]], [[mandibular prognathism]], [[Cleft lip and cleft palate|cleft lip or palate]], and [[macrocephaly]].<ref name="Spadari_2022" /> # Bilateral [[Ovarian fibroma|ovarian fibromas]] # 10% develop [[cardiac fibroma]]s # ocular abnormalities: cataracts, [[coloboma]], [[microphthalmia]].<ref name="Spadari_2022" /> # [[Meningioma|meningiomas]]<ref name="Spadari_2022" />
==Cause== Mutations in the human homologue of Drosophila patched (''[[PTCH1]]''), a tumor suppressor gene on chromosome 9, were identified as the underlying genetic event in this syndrome.<ref name="Verkouteren_2022" /> ''PTCH1'' codes for a transmembrane receptor that recognizes the Sonic Hedgehog ligand (SHH) and represses the [[Hedgehog signaling pathway|Hedgehog]] (Hh) signaling pathway.<ref name="Verkouteren_2022" /> The Hedgehog signaling pathway, which promotes cell proliferation and differentiation, is involved in more than 50% of cancers.<ref>{{cite journal | vauthors = Ebrahimi A, Larijani L, Moradi A, Ebrahimi MR | title = Hedgehog signalling pathway: carcinogenesis and targeted therapy | journal = Iranian Journal of Cancer Prevention | volume = 6 | issue = 1 | pages = 36–43 | date = Winter 2013 | pmid = 25250108 | pmc = 4142901 }}</ref> Mutations in ''PTCH1'' could reverse its inhibition of [[smoothened]] (SMO) and upregulate the Hedgehog pathway.<ref name="Verkouteren_2022" /> ''SUFU'' codes for the suppressor of fused and inhibits the Hh signaling pathway further downstream by binding to glioma-associated (GLI) transcription factors to prevent translocation to the nucleus. Mutations of ''SUFU'' are also correlated with NBCCS. When ''PTCH1'' is mutated, and SMO is no longer inhibited, ''SUFU'' becomes activated, and GLI can be translocated to the nucleus. ''SUFU'' mutations are associated with medulloblastoma, a diagnostic criterion for NBCCS.<ref name="Verkouteren_2022" /> Up to 70% of people with NBCCS inherit a ''PTCH1'' mutation, and around 4% inherit a ''SUFU'' mutation. Another 30% obtain a spontaneous, non-inherited mutation of the affected gene, resulting in the development of NBCCS.<ref>{{Cite web |title=About Gorlin Syndrome |url=https://gorlinsyndrome.org/about-gorlin-syndrome/ |access-date=2024-04-11 |website=Gorlin Syndrome Alliance |language=en}}</ref>
==Diagnosis== The most common diagnosing physicians are oral surgeons and dermatologists. However, an NBCCS diagnosis can also be made by geneticists, dentists, orthodontists, primary care physicians, Mohs surgeons, and oncologists. Though not inclusive, this list includes most healthcare providers for diagnosis.<ref>{{Cite web |title=Patient Impact Report |url=https://gorlinsyndrome.org/patient-impact-report/ |access-date=2024-04-11 |website=Gorlin Syndrome Alliance |language=en}}</ref>
NBCCS diagnoses are made by having ''two major'' or ''one major'' and ''two minor criteria''.<ref>{{Cite web |date=2018-04-03 |title=Home - Gorlin Syndrome Group |url=https://gorlingroup.org/ |access-date=2024-04-11 |language=en-GB}}</ref>
The ''major criteria'' consist of the following: # more than 2 BCCs or 1 BCC in a person younger than 20 years; # [[odontogenic keratocyst]]s of the jaw # 3 or more palmar or plantar pits # [[ectopic calcification]] or early (<20 years) calcification of the [[falx cerebri]] # bifid, fused, or splayed ribs # first-degree relative with NBCCS.
The ''minor criteria'' include the following: # [[macrocephaly]]. # [[congenital malformations]], such as [[Cleft lip and palate|cleft lip or palate]], frontal bossing, eye anomaly (cataract, [[coloboma]], microphthalmia, nystagmus). # other skeletal abnormalities, such as [[Sprengel deformity]], [[Pectus excavatum|pectus deformity]], polydactyly, [[syndactyly]] or [[hypertelorism]]. # radiologic abnormalities, such as bridging of the [[sella turcica]], vertebral anomalies, modeling defects or flame-shaped lucencies of hands and feet. # [[ovarian]] and cardio [[fibroma]] or [[medulloblastoma]] (the latter is generally found in children under two).
The first presentation of NBCCS is often odontogenic keratocysts that begin to occur, on average, around 13 years of age. Other common initial presentations include multiple BCCs before the age of 20 and medulloblastoma occurring around the age of two.<ref name="Spiker_2024" />
People with NBCCS need education about the syndrome, and may need counseling and support, as coping with the multiple BCCs and multiple surgeries is often difficult. They should reduce UV light exposure to minimize the risk of BCCs. They should also be advised that receiving [[Radiation therapy]] for their skin cancers may be contraindicated. They should look for symptoms referable to other potentially involved systems: the CNS, the genitourinary system, the cardiovascular system, and dentition.<ref name="Spadari_2022" />
[[Genetic counseling]] is advised for prospective parents, since one parent with NBCCS causes a 50% chance that their child will also be affected.<ref name="Spadari_2022" /> Genetic testing is sufficient to confirm the diagnosis when there is suspicion, but it lacks clinical diagnostic criteria. It is also beneficial for prenatal testing when there is a known family history of NBCCS.<ref name="Spiker_2024" />
==Treatment== Treatment is usually multidisciplinary, [[supportive treatment]], that is, treatment to reduce any symptoms rather than to [[cure]] the condition.<ref name="Spiker_2024" /> Having a multidisciplinary medical team is important for managing the symptoms, preventing new tumors, and providing support. Many people with NBCCS regularly see physicians and medical professionals, including a primary care physician, dermatologist, cardiologist, oral surgeon, therapist, plastic surgeon, neurologist, and gynecologist. Building a medical care team provides patients with the tools for managing their condition.<ref>{{Cite web |title=Building Your Care Team |url=https://gorlinsyndrome.org/building-your-care-team/ |access-date=2024-04-11 |website=Gorlin Syndrome Alliance |language=en}}</ref> * Enucleation of the odontogenic cysts can help, but new lesions, infections and jaw deformity are usually a result. * Patients may have numerous BCCs, which can be treated surgically or, in some patients, with topical medications. The severity of the basal-cell carcinoma determines the prognosis for most patients. Individually, BCCs rarely cause gross disfigurement, disability or death, but the scar burden and ongoing development of BCCs may be significant<ref>{{cite journal | vauthors = Cohen B, Weiss G, Yin H | title = Basal cell carcinoma (BCC) causing spinal cord compression | journal = Dermatology Online Journal | volume = 6 | issue = 1 | pages = 12 | date = September 2000 | pmid = 11328622 | doi = 10.5070/D32dj657jt }}</ref> * Genetic counseling Proper sun protection is extremely important for patients with suspected and confirmed diagnoses of NBCCS. Patients and their families should monitor for signs of NBCCS, including developmental delays, abnormal skin lesions, and odontogenic keratocysts, between visits with their multidisciplinary team.<ref name="Verkouteren_2022" />
==Incidence== NBCCS has an incidence of 1 in 50,000 to 150,000, with a higher incidence in Australia. One aspect of NBCCS is that basal-cell carcinomas will occur on areas of the body which are not generally exposed to sunlight, such as the palms and soles of the feet, and lesions may develop at the base of [[Anatomical terms of location#Hands and arms|palmar]] and [[plantar]] pits. One of the prime features of NBCCS is the development of multiple BCCs at an early age, often in the teen years. Each person with this syndrome is affected differently; some have more characteristics of the condition than others.<ref name="Spiker_2024" />
==Resources== The Gorlin Syndrome Alliance (GSA) is an organization designed to raise awareness and connect those with NBCCS or those who know someone with NBCCS. Within the entirety of the GSA community, there is a great amount of support, education, and drive for furthering research.<ref>{{Cite web |title=Gorlin Syndrome Alliance |url=https://gorlinsyndrome.org/ |access-date=2024-04-11 |website=Gorlin Syndrome Alliance |language=en}}</ref>
== See also == * [[List of cutaneous conditions]] * [[List of radiographic findings associated with cutaneous conditions]] * [[List of dental abnormalities associated with cutaneous conditions]] * [[List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer]]
== References == {{Reflist}}
== External links == {{Medical resources | DiseasesDB = 5370 | ICD10 = | ICD9 = | ICDO = | OMIM = 109400 | MedlinePlus = 001452 | eMedicineSubj = derm | eMedicineTopic = 291 }} * [https://www.ncbi.nlm.nih.gov/books/NBK1151/ GeneReviews/NCBI/NIH/UW entry on Nevoid Basal Cell Carcinoma Syndrome] * [https://www.ncbi.nlm.nih.gov/books/NBK61984/ GeneReviews/NCBI/NIH/UW entry on 9q22.3 Microdeletion] * [https://medlineplus.gov/ency/article/001452.htm US National Library of Medicine page]
{{Cell surface receptor deficiencies}} {{Authority control}}
[[Category:Cell surface receptor deficiencies]] [[Category:Epidermal nevi, neoplasms, and cysts]] [[Category:Syndromes with macrocephaly]] [[Category:Syndromes with tumors]] [[Category:Rare syndromes]] [[Category:Syndromes affecting the skin]]