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Gorlin Syndrome

Gorlin Syndrome (Nevoid Basal Cell Carcinoma Syndrome; NBCCS) — Disease Characteristics Research Report

2026-05-08
Falcon MONDO:0007187 Model: Edison Scientific Literature 24 citations

Gorlin Syndrome (Nevoid Basal Cell Carcinoma Syndrome; NBCCS) — Disease Characteristics Research Report

Target Disease

  • Disease name: Gorlin syndrome
  • Category: Mendelian (autosomal dominant tumor predisposition)
  • MONDO ID: Not available in the retrieved source set (explicit MONDO identifier not found).

Evidence base and scope

This report synthesizes the retrieved 2023–2024 primary/review literature and ClinicalTrials.gov records. Several authoritative guideline-level recommendations come from an AACR Cancer Predisposition Working Group publication in Clinical Cancer Research (Apr 2024) and real-world safety data from the NISSO post-authorization study in BMC Cancer (Nov 2024). Where specific controlled vocabulary identifiers (e.g., ICD-10/11, Orphanet, MONDO) or PMIDs were not present in the retrieved texts, this is explicitly noted.

Structured summary table

The following table is optimized for disease knowledge-base ingestion.

Table (click to expand)
Category Key facts Best supporting citations
Identifiers/Synonyms Gorlin syndrome is also called nevoid basal cell carcinoma syndrome (NBCCS), Gorlin-Goltz syndrome, basal cell nevus syndrome (BCNS), multiple basal cell carcinoma syndrome, jaw cyst-basal cell tumor-skeletal anomaly syndrome, and fifth phacomatosis. OMIM disease identifier reported as #109400; MeSH term in a Gorlin trial record is Basal Cell Nevus Syndrome (D001478). (kammoun2024theoralfacialmanifestations pages 17-25, murgia2024gorlinsyndromeassociatedbasal pages 1-2, NCT03703310 chunk 3)
Genetics Rare autosomal dominant tumor-predisposition syndrome caused primarily by loss-of-function PTCH1 variants; SUFU and occasionally PTCH2 are also implicated. About 70–80% of cases have a family history and 20–30% are de novo. PTCH1 variants account for most cases; one review excerpt states PTCH1 variants are responsible for ~90% of cases and another that germline PTCH1 mutation is present in up to 85% of NBCCS patients. (murgia2024gorlinsyndromeassociatedbasal pages 1-2, wescott2023sustainedsuppressionof pages 1-2, onodera2023hedgehogrelatedmutationcauses pages 2-4, kammoun2024theoralfacialmanifestations pages 30-34, wescott2023sustainedsuppressionof pages 2-4)
Core clinical features Common manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts (OKCs), palmar/plantar pits, falx cerebri calcification, macrocephaly, rib/vertebral anomalies, and craniofacial dysmorphism. Frequency estimates reported in a 2023 review excerpt: BCC prevalence varies by ancestry (15.2% Koreans; 38% African Americans; 80% Caucasians; 76% Australians) with mean onset ~20.3 years; OKC 75% (mean onset 15.5 years); palmar/plantar pits 87%. (onodera2023hedgehogrelatedmutationcauses pages 2-4, kammoun2024theoralfacialmanifestations pages 17-25, murgia2024gorlinsyndromeassociatedbasal pages 1-2)
Tumor risks Tumor spectrum includes BCC, medulloblastoma, ovarian fibroma, and cardiac fibroma/fibroelastoma. Medulloblastoma occurs in up to 5% overall in one review excerpt, with much higher risk in SUFU carriers than PTCH1 carriers; the 2024 AACR surveillance paper gives absolute SHH-medulloblastoma risks of about 7–9.2% for SUFU and 0.37–1.1% for PTCH1. Ovarian fibromas occur in 15–25% of patients and are often bilateral (~75% bilateral). (onodera2023hedgehogrelatedmutationcauses pages 2-4, hansford2024updateoncancer pages 3-4, zhu2023bilateralovarianfibromas pages 1-4, murgia2024gorlinsyndromeassociatedbasal pages 1-2)
Diagnostic criteria Clinical diagnosis is typically based on major/minor criteria. Major criteria summarized across 2023–2024 sources include: multiple BCCs (>5) or BCC at young age, jaw/odontogenic keratocysts, palmar/plantar pits, lamellar falx calcification, medulloblastoma, and/or an affected first-degree relative. One 2024 study states diagnosis can be made with two major + one minor or one major + three minor criteria; molecular confirmation with heterozygous germline PTCH1 or SUFU pathogenic variants can establish the diagnosis when clinical findings are inconclusive. (murgia2024gorlinsyndromeassociatedbasal pages 1-2, wescott2023sustainedsuppressionof pages 1-2, wescott2023sustainedsuppressionof pages 2-4, kammoun2024theoralfacialmanifestations pages 17-25)
Surveillance 2024 AACR childhood brain tumor predisposition guidance recommends gene-specific surveillance. For SUFU carriers: neurologic exam/head circumference in infancy and diagnosis with checks every 3–4 months until age 5; brain MRI every 3–4 months until age 3, then every 6 months until age 5. For PTCH1 carriers: routine MRI is generally not recommended; surveillance emphasizes clinical neurologic vigilance. Additional screening includes dermatologic exams with sun protection counseling, echocardiogram in infancy for cardiac fibroma, and ovarian ultrasound (PTCH1 once at age 18; SUFU every 3 years in the cited table). PTCH1-focused dental surveillance includes annual orthopantomogram/MRI. (hansford2024updateoncancer pages 3-4, hansford2024updateoncancer pages 2-3, hansford2024updateoncancer media cb459877, kammoun2024theoralfacialmanifestations pages 30-34)
Treatments Standard care includes repeated surgery for BCCs/OKCs and multidisciplinary surveillance; for high BCC burden, hedgehog pathway inhibitors (vismodegib, sonidegib) are used. In a 10-patient 2023 Gorlin case series, all patients achieved complete remission, and new BCCs fell from mean 28.3 before treatment to 1.4 during treatment; median time to a new BCC was 47.3 months. A 2024 retrospective Gorlin cohort found sustained HHI treatment suppressed both new and existing BCCs, with sonidegib appearing more effective and better tolerated than vismodegib; schedule adjustment improved tolerability without obvious loss of efficacy. (wescott2023sustainedsuppressionof pages 1-2, murgia2024gorlinsyndromeassociatedbasal pages 1-2, wescott2023sustainedsuppressionof pages 2-4)
Clinical trials Key Gorlin-specific interventional studies include NCT06050122 (Phase 3, topical patidegib gel 2% vs vehicle; active, not recruiting; primary endpoint: number of new facial BCCs at Month 12), NCT03703310 (Phase 3, patidegib topical gel 2%; completed), NCT02762084 (Phase 2, topical patidegib 2%/4% vs vehicle; completed), NCT01350115 (Phase 2, oral sonidegib/LDE225; completed), and NCT00961896 (Phase 2, topical LDE225; completed). (NCT06050122 chunk 1, NCT02762084 chunk 1, NCT01350115 chunk 1, NCT00961896 chunk 1)
Epidemiology Prevalence estimates cluster around 1:57,000, with published ranges of roughly 1:30,827 to 1:164,000; another review gives a broader estimate of 1 in 50,000 to 256,000. Reported sex distribution is similar in males and females, consistent with autosomal dominant inheritance. (murgia2024gorlinsyndromeassociatedbasal pages 1-2, wescott2023sustainedsuppressionof pages 1-2, kammoun2024theoralfacialmanifestations pages 17-25, zhu2023bilateralovarianfibromas pages 1-4)
Treatment safety / real-world implementation In the multinational NISSO real-world sonidegib safety study (321 laBCC patients; 12.2% with Gorlin syndrome), median exposure was 8.8 months. 88.5% had ≥1 TEAE; common TEAEs were muscle spasms 43.9%, dysgeusia 37.1%, and alopecia 30.2%. TEAEs led to discontinuation in 18.4%, dose reduction in 22.7%, and interruption in 30.5%; serious drug-related TEAEs occurred in 4.1%. (gutzmer2024interimanalysisof pages 1-2, gutzmer2024interimanalysisof pages 2-4)

Table: This table summarizes high-value knowledge-base facts for Gorlin syndrome, including identifiers, genetics, phenotypes, risks, surveillance, treatments, trials, and epidemiology. It emphasizes quantitative findings and recent evidence useful for structured disease annotation.

1. Disease Information

1.1 Overview (definition; current understanding)

Gorlin syndrome—also called nevoid basal cell carcinoma syndrome (NBCCS)—is a rare autosomal dominant multisystem disorder characterized by developmental anomalies and a strong predisposition to tumors, especially multiple basal cell carcinomas (BCCs) and odontogenic keratocysts (OKCs), with additional risks for medulloblastoma, ovarian fibroma, and cardiac fibroma. (murgia2024gorlinsyndromeassociatedbasal pages 1-2, onodera2023hedgehogrelatedmutationcauses pages 2-4, zhu2023bilateralovarianfibromas pages 1-4)

Recent expert framing (2024): A 2024 retrospective cohort paper defines NBCCS/GS as “a genetic disorder characterized by the development of multiple cutaneous BCCs due to mutations in the hedgehog signaling pathway.” (Cancers, published online 2024-06-07; DOI URL below). (murgia2024gorlinsyndromeassociatedbasal pages 1-2)

1.2 Key identifiers

  • OMIM (disease): #109400 (explicitly listed). (kammoun2024theoralfacialmanifestations pages 17-25)
  • MeSH (disease term used in ClinicalTrials.gov): “Basal Cell Nevus Syndrome” D001478 (ClinicalTrials.gov record metadata). (NCT03703310 chunk 3)
  • Other identifiers (Orphanet, ICD-10/ICD-11, MONDO): Not present in the retrieved evidence snippets; therefore not reported here.

1.3 Synonyms and alternative names

Common synonyms include: - Nevoid basal cell carcinoma syndrome (NBCCS) - Basal cell nevus syndrome (BCNS) - Gorlin–Goltz syndrome - Multiple basal cell carcinoma syndrome - Jaw cyst–basal cell tumor–skeletal anomaly syndrome - Fifth phacomatosis (kammoun2024theoralfacialmanifestations pages 17-25, murgia2024gorlinsyndromeassociatedbasal pages 1-2)

1.4 Source type

Information summarized here is drawn from aggregated disease-level resources (reviews/guidelines) and clinical cohorts/case series (including real-world observational safety data) rather than EHR-derived phenotyping. (hansford2024updateoncancer pages 3-4, gutzmer2024interimanalysisof pages 2-4, wescott2023sustainedsuppressionof pages 1-2)

2. Etiology

2.1 Disease causal factors

Primary cause: germline pathogenic variants in Hedgehog (Hh) pathway negative regulators—most commonly PTCH1, and less commonly SUFU and PTCH2—leading to pathway hyperactivation with developmental anomalies and tumor predisposition. (onodera2023hedgehogrelatedmutationcauses pages 2-4, murgia2024gorlinsyndromeassociatedbasal pages 1-2)

Inheritance: autosomal dominant; a large fraction arises de novo (20–30% in multiple reports). (murgia2024gorlinsyndromeassociatedbasal pages 1-2, wescott2023sustainedsuppressionof pages 1-2)

2.2 Risk factors

Genetic risk factors

Environmental/medical exposure risk factors

  • Ionizing radiation should be avoided when feasible due to tumor induction concerns in NBCCS; this is emphasized in pediatric surveillance guidance (sun protection counseling and avoidance of ionizing radiation are explicitly noted). (hansford2024updateoncancer pages 2-3)

2.3 Protective factors / gene–environment interactions

No explicit protective genetic variants or quantified gene–environment interaction models were found in the retrieved evidence set. Risk mitigation is primarily via exposure avoidance (radiation, UV) and surveillance. (hansford2024updateoncancer pages 2-3)

3. Phenotypes (clinical features)

3.1 High-frequency phenotypes and reported frequencies

A 2023 review focusing on Hedgehog-related skeletal/tumor disorders provides quantitative phenotype frequencies for Gorlin syndrome: - Palmar/plantar pits: ~87% (onodera2023hedgehogrelatedmutationcauses pages 2-4) - Odontogenic keratocysts (OKC): ~75%, mean onset ~15.5 years (onodera2023hedgehogrelatedmutationcauses pages 2-4) - Basal cell carcinoma (BCC): frequency varies by ancestry (reported values: 15.2% Koreans; 38% African Americans; 80% Caucasians; 76% Australians) with mean onset ~20.3 years (onodera2023hedgehogrelatedmutationcauses pages 2-4) - Medulloblastoma: “up to 5% in the first 2 years of life” in the cited review summary (onodera2023hedgehogrelatedmutationcauses pages 2-4)

Other commonly described manifestations across 2023–2024 clinical series/reviews include macrocephaly, craniofacial dysmorphism, rib/vertebral anomalies, falx cerebri calcification, and multiple BCCs (often dozens to hundreds over a lifetime). (wescott2023sustainedsuppressionof pages 1-2, kammoun2024theoralfacialmanifestations pages 17-25, murgia2024gorlinsyndromeassociatedbasal pages 1-2)

3.2 Example phenotype-to-HPO suggestions (non-exhaustive)

The retrieved texts did not include formal HPO mappings; below are suggested HPO-aligned phenotype labels for knowledge-base normalization (term IDs should be resolved against the HPO release used in your KB pipeline): - Multiple basal cell carcinomas → Basal cell carcinoma - Odontogenic keratocysts → Odontogenic keratocyst - Palmar/plantar pits → Palmar pits, Plantar pits - Macrocephaly → Macrocephaly - Falx cerebri calcification → Intracranial calcification / Falx cerebri calcification - Rib anomalies (e.g., bifid ribs) → Bifid rib / Rib anomaly - Medulloblastoma (SHH-activated) → Medulloblastoma - Ovarian fibroma → Ovarian fibroma - Cardiac fibroma → Cardiac fibroma

3.3 Quality of life impact

High BCC burden can lead to repeated procedures and disfigurement; a 2024 cohort describes that patients “may need dozens or even hundreds of surgical procedures in their lifetime,” which can be severely scarring/disfiguring, motivating systemic pathway-targeted therapies. (murgia2024gorlinsyndromeassociatedbasal pages 1-2)

4. Genetic / Molecular Information

4.1 Causal genes

4.2 Pathogenic variant types and functional consequences

Mechanistic class: typically loss-of-function of pathway repressors → constitutive pathway signaling. In PTCH1-associated disease, PTCH1 normally represses SMO; loss leads to downstream GLI activation. (onodera2023hedgehogrelatedmutationcauses pages 2-4)

Hard-to-detect variant class (2024 development): Mochizuki et al. describe a germline mobile-element insertion in PTCH1 (Alu insertion) that standard panel and genome sequencing did not initially detect, requiring manual review and RNA-seq confirmation: - Variant: PTCH1 c.361_362insAlu (molecular confirmation via clinical RNA sequencing) (mochizuki2024germlineptch1c.361362insalu pages 1-2, mochizuki2024germlineptch1c.361362insalu pages 3-4) - Clinical implication: supports integrating RNA-seq with DNA testing for cryptic splicing/insertion events when phenotype is strong. (mochizuki2024germlineptch1c.361362insalu pages 2-3)

Direct abstract quote (diagnostic genomics; 2024): “Clinical RNA sequencing further demonstrated an Alu insertion at this region (PTCH1: c.361_362insAlu), providing molecular confirmation of Gorlin syndrome.” (Mochizuki et al., Am J Med Genet A, Jun 2024; https://doi.org/10.1002/ajmg.a.63788). (mochizuki2024germlineptch1c.361362insalu pages 1-2)

4.3 Modifier genes / epigenetics / chromosomal abnormalities

The retrieved evidence mentions SUFU/PTCH2 as contributors/modifiers of expressivity but does not provide specific validated modifier loci, epigenetic signatures, or recurrent chromosomal abnormalities. (murgia2024gorlinsyndromeassociatedbasal pages 1-2)

5. Environmental Information

5.1 Environmental/lifestyle factors

The retrieved 2024 pediatric surveillance guideline emphasizes sun protection counseling and avoidance of ionizing radiation due to tumor risks in NBCCS. (hansford2024updateoncancer pages 2-3)

No additional quantified toxin/occupational exposure associations were present in the retrieved evidence set.

6. Mechanism / Pathophysiology

6.1 Core pathway: Hedgehog signaling dysregulation

A 2023 mechanistic review describes Gorlin syndrome as involving mutations in negative regulators (PTCH1/PTCH2/SUFU) of the Hedgehog pathway. PTCH1 encodes a multipass transmembrane receptor for SHH/IHH/DHH ligands and represses SMO; PTCH1 loss leads to constitutive SMO activation and aberrant activation of GLI transcription factors, driving developmental anomalies and tumorigenesis. (onodera2023hedgehogrelatedmutationcauses pages 2-4)

6.2 Causal chain (gene → pathway → cell behavior → phenotype)

6.3 Suggested GO / CL annotations (for KB normalization)

The retrieved sources do not provide explicit GO/CL terms; plausible normalizations consistent with described biology include: - GO biological process (suggestions): Hedgehog signaling pathway; regulation of cell proliferation; embryonic skeletal system development; epithelial cell proliferation. - CL cell types (suggestions): basal keratinocyte; hair follicle epithelial cell; odontogenic epithelial cell; cerebellar granule neuron precursor (relevant to SHH-medulloblastoma).

7. Anatomical Structures Affected

7.1 Organ/tissue systems (high-confidence from retrieved evidence)

7.2 Suggested UBERON mappings (labels)

  • Skin; jaw; cerebellum/brain; ovary; heart.

8. Temporal Development (natural history)

8.1 Onset patterns

8.2 Progression/course

The disease course is lifelong with repeated tumor occurrence (particularly BCCs), often requiring repeated local treatments or systemic pathway inhibition when burden is high. (wescott2023sustainedsuppressionof pages 1-2, murgia2024gorlinsyndromeassociatedbasal pages 1-2)

9. Inheritance and Population

9.1 Inheritance

Autosomal dominant. (kammoun2024theoralfacialmanifestations pages 30-34, murgia2024gorlinsyndromeassociatedbasal pages 1-2)

9.2 De novo rate

Across 2023–2024 sources, ~20–30% of cases are attributed to de novo pathogenic variation, with ~70–80% having family history. (murgia2024gorlinsyndromeassociatedbasal pages 1-2, wescott2023sustainedsuppressionof pages 1-2)

9.3 Epidemiology (prevalence)

Prevalence estimates in the retrieved sources cluster around: - ~1:57,000 with a reported range 1:30,827–1:164,000 (northwest England estimate cited in 2024 cohort and 2023 case series). (murgia2024gorlinsyndromeassociatedbasal pages 1-2, wescott2023sustainedsuppressionof pages 1-2) - A broader estimate of 1 in 50,000 to 256,000 is also reported in a 2024 review excerpt. (kammoun2024theoralfacialmanifestations pages 17-25)

9.4 Sex ratio

Similar rates in males and females are expected/observed given autosomal dominant inheritance (explicitly stated in a 2023 case-series excerpt). (wescott2023sustainedsuppressionof pages 1-2)

10. Diagnostics

10.1 Clinical diagnostic criteria (major/minor)

Across 2023–2024 sources, diagnosis is described as based on combinations of major/minor criteria.

Major criteria (commonly listed): - Multiple BCCs or early-onset BCC burden (e.g., >5 or BCC at young age) - Jaw odontogenic keratocysts - Palmar/plantar pits - Lamellar calcification of the falx cerebri - Medulloblastoma - First-degree relative with NBCCS (murgia2024gorlinsyndromeassociatedbasal pages 1-2, wescott2023sustainedsuppressionof pages 1-2)

Rule-based diagnosis (example reported in 2024 cohort): “two major + one minor, or one major + three minor criteria.” (murgia2024gorlinsyndromeassociatedbasal pages 1-2)

10.2 Molecular diagnosis and genetic testing strategy

Key concept: Molecular confirmation with heterozygous germline PTCH1 or SUFU pathogenic variants can establish diagnosis when clinical features are incomplete. (wescott2023sustainedsuppressionof pages 2-4)

2024 development (DNA+RNA sequencing): Mochizuki et al. show that standard clinical DNA approaches (panel/GS) may miss mobile-element insertions; paired tumor/normal exome plus RNA-seq can provide confirmation (PTCH1 c.361_362insAlu). (mochizuki2024germlineptch1c.361362insalu pages 1-2, mochizuki2024germlineptch1c.361362insalu pages 3-4)

10.3 Imaging and other testing

  • Dental imaging (orthopantomogram) is explicitly included in surveillance/diagnostic workflows for PTCH1 carriers; MRI can substitute in some guidance. (hansford2024updateoncancer pages 2-3, hansford2024updateoncancer media cb459877)
  • Brain MRI for medulloblastoma surveillance is recommended in SUFU carriers in early childhood (see §11). (hansford2024updateoncancer pages 2-3)

10.4 Differential diagnosis

No explicit differential diagnosis list was present in the retrieved evidence snippets.

11. Outcome / Prognosis

11.1 Tumor risks and prognostic stratification (gene-specific)

A key 2024 guideline update provides absolute SHH-medulloblastoma risks: - SUFU: ~7%–9.2% - PTCH1: ~0.37%–1.1% (hansford2024updateoncancer pages 3-4)

This genotype risk stratification drives surveillance intensity (SUFU vs PTCH1; see below). (hansford2024updateoncancer pages 3-4, hansford2024updateoncancer pages 2-3)

11.2 Morbidity and burden

The principal morbidity in many patients stems from repeated BCC occurrence and associated procedural burden/disfigurement, motivating systemic therapies when local therapy becomes impractical. (murgia2024gorlinsyndromeassociatedbasal pages 1-2, wescott2023sustainedsuppressionof pages 1-2)

12. Treatment

12.1 Local/surgical management (current practice)

Patients frequently undergo repeated excisions or other local therapies for BCCs and management of OKCs; the 2024 cohort emphasizes high lifetime procedural burden (“dozens or even hundreds of surgical procedures”). (murgia2024gorlinsyndromeassociatedbasal pages 1-2)

12.2 Targeted pharmacotherapy: Hedgehog pathway inhibitors (HHIs)

Agents: vismodegib and sonidegib (SMO inhibitors) are used to suppress BCC development in high-burden NBCCS patients. (wescott2023sustainedsuppressionof pages 1-2, murgia2024gorlinsyndromeassociatedbasal pages 1-2)

Effectiveness in Gorlin syndrome cohorts (2023–2024): - In a 10-patient case series (published 2023-10; Current Oncology; https://doi.org/10.3390/curroncol30100661), “All patients achieved a complete remission,” and mean new tumors decreased from 28.3 before treatment to 1.4 during treatment (p=0.0048); median time to a new BCC was 47.3 months. (wescott2023sustainedsuppressionof pages 1-2) - In a 16-patient retrospective series (published 2024-06-07; Cancers; https://doi.org/10.3390/cancers16122166), sustained HHI therapy suppressed both new and existing BCCs, and sonidegib was reported as having superior efficacy and safety vs vismodegib, with schedule adjustments improving tolerability. (murgia2024gorlinsyndromeassociatedbasal pages 1-2)

Adverse effects (class effects): muscle cramps/spasms, taste changes (dysgeusia), alopecia, fatigue/asthenia are commonly noted. (wescott2023sustainedsuppressionof pages 1-2, wescott2023sustainedsuppressionof pages 2-4)

12.3 Real-world implementation and safety (2024 post-authorization data)

The NISSO non-interventional post-authorization sonidegib study (published 2024-11; BMC Cancer; https://doi.org/10.1186/s12885-024-13101-z) enrolled 321 laBCC patients (median age 77), including 12.2% (n=39) with Gorlin syndrome. (gutzmer2024interimanalysisof pages 2-4)

Key safety statistics: - ≥1 TEAE: 88.5% - Most common TEAEs: muscle spasms 43.9%, dysgeusia 37.1%, alopecia 30.2% - TEAE-related: discontinuation 18.4%, dose reduction 22.7%, interruption 30.5% - Serious drug-related TEAEs: 4.1% (gutzmer2024interimanalysisof pages 2-4)

12.4 MAXO suggestions (treatment actions)

Suggested MAXO-normalizations (labels) consistent with described management: - Hedgehog pathway inhibitor therapy - Dermatologic surveillance - Surgical excision of basal cell carcinoma - Dental/maxillofacial surgery for odontogenic keratocysts - Genetic counseling

13. Prevention

13.1 Primary/secondary prevention

Guideline-level prevention focuses on: - Sun protection counseling - Avoidance of ionizing radiation when feasible - Surveillance to detect medulloblastoma and other tumors early (gene-specific) (hansford2024updateoncancer pages 2-3)

13.2 Surveillance (gene-specific; 2024 AACR guidance)

The 2024 AACR working group recommends gene-tailored surveillance, particularly for early childhood SHH-medulloblastoma. (hansford2024updateoncancer pages 3-4)

Key surveillance elements for Gorlin syndrome (from Table 1): - SUFU carriers: brain MRI q3–4 months until age 3, then q6 months until age 5; neurologic exam/head circumference checks q3–4 months until age 5. (hansford2024updateoncancer pages 2-3, hansford2024updateoncancer media cb459877) - PTCH1 carriers: routine neuroimaging generally not recommended; emphasize clinical vigilance; dental and jaw surveillance using orthopantomogram or MRI. (hansford2024updateoncancer pages 3-4, hansford2024updateoncancer media cb459877) - Echocardiogram: baseline in infancy (<6 months) to evaluate cardiac fibroma. (hansford2024updateoncancer pages 2-3, hansford2024updateoncancer media cb459877) - Ovarian ultrasound: per Table 1, PTCH1 “once at 18 years,” SUFU “every 3 years starting at 5 years” (and MRI substitution if ultrasound not feasible). (hansford2024updateoncancer pages 2-3, hansford2024updateoncancer media cb459877)

Visual evidence: the extracted Table 1 image segment containing these intervals is provided in the cited figure. (hansford2024updateoncancer media cb459877)

14. Other Species / Natural Disease

No evidence for naturally occurring Gorlin syndrome analogs in non-human species was found in the retrieved sources.

15. Model Organisms

The retrieved 2023–2024 evidence set did not include explicit descriptions of specific named engineered animal models (e.g., Ptch1+/− mice) or in vitro models, beyond general statements that Hedgehog signaling is essential in development and tumorigenesis. This is an evidence gap in the current retrieval and should be filled by targeted searches of model organism databases (MGI/IMPC) if required for your KB. (onodera2023hedgehogrelatedmutationcauses pages 2-4)

Recent developments (2023–2024 highlights)

  1. Gene-specific surveillance refined for childhood SHH-medulloblastoma risk: SUFU carriers receive routine MRI surveillance in early childhood, while PTCH1 carriers generally do not, reflecting the large absolute risk differential. (Clin Cancer Res, 2024-04; https://doi.org/10.1158/1078-0432.ccr-23-4033). (hansford2024updateoncancer pages 3-4, hansford2024updateoncancer pages 2-3)
  2. Diagnostics advancing beyond standard DNA panels: 2024 evidence shows RNA sequencing can confirm cryptic mobile-element insertions in PTCH1 missed by routine testing, supporting DNA+RNA workflows in strong clinical suspicion cases. (Am J Med Genet A, 2024-06; https://doi.org/10.1002/ajmg.a.63788). (mochizuki2024germlineptch1c.361362insalu pages 1-2, mochizuki2024germlineptch1c.361362insalu pages 3-4)
  3. Real-world HHI tolerability quantified in routine practice (including Gorlin subgroup): NISSO provides contemporary AE/discontinuation rates for sonidegib, with 12.2% Gorlin patients. (BMC Cancer, 2024-11; https://doi.org/10.1186/s12885-024-13101-z). (gutzmer2024interimanalysisof pages 2-4)
  4. New prevention-focused topical Hh inhibitor trials ongoing: Phase 3 topical patidegib (2%) prevention trial active (not recruiting) targeting reduction of new facial BCCs in PTCH1-confirmed Gorlin syndrome. (ClinicalTrials.gov NCT06050122; start 2024-03-17). (NCT06050122 chunk 1)

Key URLs and publication dates (selected)

Limitations of this report (due to retrieved evidence)

  • PMIDs were not present in the retrieved tool excerpts; DOIs and ClinicalTrials.gov identifiers are provided instead.
  • ICD-10/ICD-11, Orphanet, and MONDO identifiers were not found in the retrieved texts.
  • Model organism evidence was not directly retrieved; additional targeted searches are required for that section.

References

  1. (kammoun2024theoralfacialmanifestations pages 17-25): K Kammoun. The oral-facial manifestations of gorlin syndrome. Unknown journal, 2024.

  2. (murgia2024gorlinsyndromeassociatedbasal pages 1-2): Giulia Murgia, Luca Valtellini, Nerina Denaro, Gianluca Nazzaro, Paolo Bortoluzzi, Valentina Benzecry, Emanuela Passoni, and Angelo Valerio Marzano. Gorlin syndrome-associated basal cell carcinomas treated with vismodegib or sonidegib: a retrospective study. Cancers, 16:2166, Jun 2024. URL: https://doi.org/10.3390/cancers16122166, doi:10.3390/cancers16122166. This article has 15 citations.

  3. (NCT03703310 chunk 3): Study of Patidegib Topical Gel, 2%, for the Reduction of Disease Burden of Persistently Developing Basal Cell Carcinomas (BCCs) in Subjects With Basal Cell Nevus Syndrome (Gorlin Syndrome). Sol-Gel Technologies, Ltd.. 2019. ClinicalTrials.gov Identifier: NCT03703310

  4. (wescott2023sustainedsuppressionof pages 1-2): Raquel Wescott and Wolfram Samlowski. Sustained suppression of gorlin syndrome-associated basal cell carcinomas with vismodegib or sonidegib: a case series. Current Oncology, 30:9156-9167, Oct 2023. URL: https://doi.org/10.3390/curroncol30100661, doi:10.3390/curroncol30100661. This article has 7 citations.

  5. (onodera2023hedgehogrelatedmutationcauses pages 2-4): Shoko Onodera and Toshifumi Azuma. Hedgehog-related mutation causes bone malformations with or without hereditary gene mutations. International Journal of Molecular Sciences, 24:12903, Aug 2023. URL: https://doi.org/10.3390/ijms241612903, doi:10.3390/ijms241612903. This article has 10 citations.

  6. (kammoun2024theoralfacialmanifestations pages 30-34): K Kammoun. The oral-facial manifestations of gorlin syndrome. Unknown journal, 2024.

  7. (wescott2023sustainedsuppressionof pages 2-4): Raquel Wescott and Wolfram Samlowski. Sustained suppression of gorlin syndrome-associated basal cell carcinomas with vismodegib or sonidegib: a case series. Current Oncology, 30:9156-9167, Oct 2023. URL: https://doi.org/10.3390/curroncol30100661, doi:10.3390/curroncol30100661. This article has 7 citations.

  8. (hansford2024updateoncancer pages 3-4): Jordan R. Hansford, Anirban Das, Rose B. McGee, Yoshiko Nakano, Jack Brzezinski, Sarah R. Scollon, Surya P. Rednam, Jaclyn Schienda, Orli Michaeli, Sun Young Kim, Mary-Louise C. Greer, Rosanna Weksberg, Douglas R. Stewart, William D. Foulkes, Uri Tabori, Kristian W. Pajtler, Stefan M. Pfister, Garrett M. Brodeur, and Junne Kamihara. Update on cancer predisposition syndromes and surveillance guidelines for childhood brain tumors. Clinical cancer research : an official journal of the American Association for Cancer Research, 30:2342-2350, Apr 2024. URL: https://doi.org/10.1158/1078-0432.ccr-23-4033, doi:10.1158/1078-0432.ccr-23-4033. This article has 51 citations.

  9. (zhu2023bilateralovarianfibromas pages 1-4): Menghan Zhu, Jun Li, Jie Duan, Jing Yang, Weiyong Gu, and Wei Jiang. Bilateral ovarian fibromas as the sole manifestation of gorlin syndrome in a 22-year-old woman: a case report and literature review. Diagnostic Pathology, Oct 2023. URL: https://doi.org/10.1186/s13000-023-01406-9, doi:10.1186/s13000-023-01406-9. This article has 3 citations and is from a peer-reviewed journal.

  10. (hansford2024updateoncancer pages 2-3): Jordan R. Hansford, Anirban Das, Rose B. McGee, Yoshiko Nakano, Jack Brzezinski, Sarah R. Scollon, Surya P. Rednam, Jaclyn Schienda, Orli Michaeli, Sun Young Kim, Mary-Louise C. Greer, Rosanna Weksberg, Douglas R. Stewart, William D. Foulkes, Uri Tabori, Kristian W. Pajtler, Stefan M. Pfister, Garrett M. Brodeur, and Junne Kamihara. Update on cancer predisposition syndromes and surveillance guidelines for childhood brain tumors. Clinical cancer research : an official journal of the American Association for Cancer Research, 30:2342-2350, Apr 2024. URL: https://doi.org/10.1158/1078-0432.ccr-23-4033, doi:10.1158/1078-0432.ccr-23-4033. This article has 51 citations.

  11. (hansford2024updateoncancer media cb459877): Jordan R. Hansford, Anirban Das, Rose B. McGee, Yoshiko Nakano, Jack Brzezinski, Sarah R. Scollon, Surya P. Rednam, Jaclyn Schienda, Orli Michaeli, Sun Young Kim, Mary-Louise C. Greer, Rosanna Weksberg, Douglas R. Stewart, William D. Foulkes, Uri Tabori, Kristian W. Pajtler, Stefan M. Pfister, Garrett M. Brodeur, and Junne Kamihara. Update on cancer predisposition syndromes and surveillance guidelines for childhood brain tumors. Clinical cancer research : an official journal of the American Association for Cancer Research, 30:2342-2350, Apr 2024. URL: https://doi.org/10.1158/1078-0432.ccr-23-4033, doi:10.1158/1078-0432.ccr-23-4033. This article has 51 citations.

  12. (NCT06050122 chunk 1): Efficacy and Safety of Patidegib Gel 2% for Preventing Basal Cell Carcinomas on the Face of Adults With Gorlin Syndrome. Sol-Gel Technologies, Ltd.. 2024. ClinicalTrials.gov Identifier: NCT06050122

  13. (NCT02762084 chunk 1): Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas in Gorlin Syndrome Patients. PellePharm, Inc.. 2016. ClinicalTrials.gov Identifier: NCT02762084

  14. (NCT01350115 chunk 1): Efficacy, Safety and Pharmacokinetics of Oral LDE225 in Treatment of Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS). Novartis Pharmaceuticals. 2011. ClinicalTrials.gov Identifier: NCT01350115

  15. (NCT00961896 chunk 1): A Trial to Evaluate the Safety, Local Tolerability, Pharmacokinetics and Pharmacodynamics of LDE225 on Skin Basal Cell Carcinomas in Gorlin Syndrome Patients. Novartis Pharmaceuticals. 2009. ClinicalTrials.gov Identifier: NCT00961896

  16. (gutzmer2024interimanalysisof pages 1-2): Ralf Gutzmer, Ulrike Leiter, Peter Mohr, Katharina C. Kähler, Paolo Antonio Ascierto, Massimiliano Scalvenzi, Ketty Peris, Gemma María Pérez-Pastor, Ricardo Fernández-de-Misa, Rafael Botella-Estrada, Robert E. Hunger, Serena Martelli, Nur Güneli, Ramon Arntz, and Axel Hauschild. Interim analysis of the multinational, post-authorization safety study (nisso) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma. BMC Cancer, Nov 2024. URL: https://doi.org/10.1186/s12885-024-13101-z, doi:10.1186/s12885-024-13101-z. This article has 11 citations and is from a peer-reviewed journal.

  17. (gutzmer2024interimanalysisof pages 2-4): Ralf Gutzmer, Ulrike Leiter, Peter Mohr, Katharina C. Kähler, Paolo Antonio Ascierto, Massimiliano Scalvenzi, Ketty Peris, Gemma María Pérez-Pastor, Ricardo Fernández-de-Misa, Rafael Botella-Estrada, Robert E. Hunger, Serena Martelli, Nur Güneli, Ramon Arntz, and Axel Hauschild. Interim analysis of the multinational, post-authorization safety study (nisso) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma. BMC Cancer, Nov 2024. URL: https://doi.org/10.1186/s12885-024-13101-z, doi:10.1186/s12885-024-13101-z. This article has 11 citations and is from a peer-reviewed journal.

  18. (mochizuki2024germlineptch1c.361362insalu pages 1-2): Aaron Y. Mochizuki, Chinmayee B. Nagaraj, Douglas Depoorter, Kathleen M. Schieffer, and Sun Young Kim. Germline ptch1: c.361_362insalu alteration identified by comprehensive exome and rna sequencing in a patient with gorlin syndrome. American Journal of Medical Genetics Part A, Jun 2024. URL: https://doi.org/10.1002/ajmg.a.63788, doi:10.1002/ajmg.a.63788. This article has 1 citations.

  19. (mochizuki2024germlineptch1c.361362insalu pages 3-4): Aaron Y. Mochizuki, Chinmayee B. Nagaraj, Douglas Depoorter, Kathleen M. Schieffer, and Sun Young Kim. Germline ptch1: c.361_362insalu alteration identified by comprehensive exome and rna sequencing in a patient with gorlin syndrome. American Journal of Medical Genetics Part A, Jun 2024. URL: https://doi.org/10.1002/ajmg.a.63788, doi:10.1002/ajmg.a.63788. This article has 1 citations.

  20. (mochizuki2024germlineptch1c.361362insalu pages 2-3): Aaron Y. Mochizuki, Chinmayee B. Nagaraj, Douglas Depoorter, Kathleen M. Schieffer, and Sun Young Kim. Germline ptch1: c.361_362insalu alteration identified by comprehensive exome and rna sequencing in a patient with gorlin syndrome. American Journal of Medical Genetics Part A, Jun 2024. URL: https://doi.org/10.1002/ajmg.a.63788, doi:10.1002/ajmg.a.63788. This article has 1 citations.