gorlin's syndrome

Targeting the mammalian target of rapamycin (mTOR) pathway represents a potentially novel approach to treat basal cell carcinoma (BCC), but activation of this pathway has not been well described in human BCCs. The purpose of this study was to assess whether mTOR pathway activation occurs in BCCs (both sporadic and syndromic) and report a case of a patient with Gorlin syndrome (GS) whose clinically suspicious BCCs responded to mTOR inhibition through topical sirolimus treatment. After Stanford Institutional Review Board Approval, archived BCCs from patients with GS (n = 25), sporadic BCCs (n = 35), and control tissues were subjected to immunohistochemical analysis for the activation of mTOR pathway, and immunohistochemical staining intensity was evaluated by a dermatopathologist...

The Nitrosogenesis of skin cancer is a modern newly introduced concept in medicine, mainly concerning melanoma, but also keratinocytic cancers such as basal cell carcinoma. The nitroso-contamination of more than 300 drugs worldwide and the permanent (relatively short-term) intake of mutagen-contaminated drugs could create serious prerequisites for the development of skin cancer. Retrospective but also prospective analyses following potentially contaminated polymedication with a heterogeneous type of nitrosamines in real patients are indicative of a causal connection rather than a sporadic association between 1) intake of a possibly nitrosamine-contaminated drug and 2) generation of keratinocytic skin cancer...

OBJECTIVE: To analyse the aetiology and pathogenesis of Gorlin-Goltz syndrome (GS; also known as nevoid basal cell carcinoma syndrome [NBCCS] or basal cell nevus syndrome [BCNS]) in a Chinese family. METHODS: Whole-exome sequencing (WES) was performed on genomic DNA samples from the subjects in a family, followed by the investigation of pathogenesis via bioinformatic approaches and conformational analysis. RESULTS: A novel heterozygous non-frameshift deletion patched 1 (PTCH1) [NM_000264: c...

Gorlin-Goltz syndrome (GGS) is an infrequent multisystemic disease with an autosomal dominant trait, which depicted presence of numerous basal cell carcinoma in conjunction with multiorgan abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the keratocystic odontogenic tumour are usually one of the first manifestations of the syndrome. This article includes a case report of the GGS with regard to its history, incidence, etiology, features, investigations, diagnostic criteria, keratocystic odontogenic tumour and treatment modalities...

Biallelic pathogenic variants in CDC45 are associated with Meier-Gorlin syndrome with craniosynostosis (MGORS type 7), which also includes short stature and absent/hypoplastic patellae. Identified variants act through a hypomorphic loss of function mechanism, to reduce CDC45 activity and impact DNA replication initiation. In addition to missense and premature termination variants, several pathogenic synonymous variants have been identified, most of which cause increased exon skipping of exon 4, which encodes an essential part of the RecJ-orthologue's DHH domain...

OBJECTIVE: Although Gorlin syndrome has rich skin findings, there is limited information about their subtypes, features specific to this genodermatosis, and relationships with each other. MATERIALS AND METHODS: The demographic characteristics as well as cutaneous and extracutaneous findings of consecutive Gorlin syndrome patients diagnosed during 23 years were evaluated retrospectively. The relationship between palmoplantar pitting and basal cell carcinoma (BCC) in this localization and the relationship between odontogenic keratocysts (OKCs) and epidermoid cysts were investigated...

Gorlin-Goltz syndrome (GGS) is a rare hereditary disease characterized by multiple basal cell carcinomas, odontogenic keratocyst (OKCs) and musculoskeletal malformations. Pathogenesis of the syndrome is attributed to abnormalities in the long arm of chromosome 9 (q22.3-q31) and mutations in the human patched gene (PTCH1 gene). Here, we report a rare case of an incidental finding of GGS in an 18-year-old male patient presenting multiple OKCs, calcification of the falx cerebri, and bifid rib.

Odontogenic keratocyst (OKC) is a common jaw cyst with a high recurrence rate. OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome. Moreover, OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts. Because of the different prognosis, differential diagnosis of several cysts can contribute to clinical management. We collected 519 cases, comprising a total of 2 157 hematoxylin and eosin-stained images, to develop digital pathology-based artificial intelligence (AI) models for the diagnosis and prognosis of OKC...

Odontogenic keratocysts (OKCs) are a common presentation in almost all patients with nevoid basal cell carcinoma syndrome (NBCCS) or Gorlin syndrome, irrespective of race. In most patients with NBCCS, OKC presents as multiple lesions affecting the jaws which makes it a signpost for the investigation of patients with the syndrome. In approximately 40% of pediatric patients, the initial presentation is that of a single OKC, which may often result in missing the diagnosis of NBCCS. This is particularly common in patients without clinically apparent NBCCS-related manifestations...

Goltz-Gorlin syndrome is a rare X-linked inherited disorder associated with PORCN (porcupine homolog-Drosophila) gene mutation. It primarily affects the skin and its appendages. The characteristic cutaneous features include a blaschko-linear pattern, skin atrophy, pigmentary changes, and telangiectasia. The oral manifestations have been reported in more than half of the affected individuals. The most common oral findings include enamel hypoplasia, hypodontia, supernumerary teeth, microdontia, vertical grooving of the teeth, taurodontism, fusion, and abnormal root morphology reported in sporadic cases...

Gorlin syndrome, also known as basal cell nevus syndrome, is an autosomal dominant genetic disorder that predisposes humans to tumors. In most cases, this syndrome results from inactivating mutations in the patched homologue 1 gene. Basal cell carcinomas are one of the main characteristics of this syndrome and serve as a major diagnostic criterion. Gorlin syndrome shows a variable phenotype, and recently, other less common mutations in the suppressor of fused homologue or patched homologue 2 genes have been documented in individuals with this syndrome...

Progeroid disorders are a heterogenous group of rare and complex hereditary syndromes presenting with pleiotropic phenotypes associated with normal aging. Due to the large variation in clinical presentation the diseases pose a diagnostic challenge for clinicians which consequently restricts medical research. To accommodate the challenge, we compiled a list of known progeroid syndromes and calculated the mean prevalence of their associated phenotypes, defining what we term the 'progeria phenome'. The data were used to train a support vector machine that is available at https://www...

PURPOSE: Odontogenic keratocysts (OKCs) have high recurrence rates. We aimed to identify recurrence patterns in OKCs and the onset of second primary OKCs in non-syndromic and syndromic patients. MATERIAL AND METHODS: Patients with OKCs reporting to our department from 1998 to 2021 (23 years) were retrospectively evaluated using demographic, clinical (age, sex, location, and size), histopathological, radiographic, and treatment data. All patients were followed-up for > 3 years and evaluated for OKC recurrence...

In 2002, heterozygous suppressor of fused variants (SUFU+/- ) in the germline were described to have a tumor suppressor role in the development of pediatric medulloblastoma (MB). Other neoplasms associated with pathologic germline SUFU+/- variants have also been described among patients with basal cell nevus syndrome (BCNS; BCNS is also known as Gorlin syndrome, nevoid basal cell carcinoma [BCC] syndrome or Gorlin-Goltz syndrome; OMIM 109400), an autosomal-dominant cancer predisposition syndrome. The phenotype of patients with germline SUFU+/- variants is very poorly characterized due to a paucity of large studies with long-term follow-up...

Understanding human DNA replication through the study of yeast has been an extremely fruitful journey. The minichromosome maintenance (MCM) 2-7 genes that encode the catalytic core of the eukaryotic replisome were initially identified through forward yeast genetics. The origin recognition complexes (ORC) that load the MCM hexamers at replication origins were purified from yeast extracts. We have reached an age where high-resolution cryoEM structures of yeast and human replication complexes can be compared side-by-side...

Cardiac tumours can occur in association with genetic syndromes. Rhabdomyomas have been reported in association with tuberous sclerosis, myxomas with Carney's complex, cardiac fibromas with Gorlin syndrome, and paragangliomas with multiple endocrine neoplasm syndrome. The presentation and prognosis of cardiac tumours associated with genetic syndromes differ compared with sporadic cases. Knowledge about the associated syndromes' genetic features and extracardiac manifestations is essential for the diagnosis, prognosis, and management of cardiac neoplasms...

For over a decade, it has been known that yeast Sld2, Dpb11, GINS and Polε form the pre-loading complex (pre-LC), which is recruited to a CDC45-bound MCM2-7 complex by the Sld3/Sld7 heterodimer in a phospho-dependent manner. Whilst functional orthologs of Dbp11 (TOPBP1), Sld3 (TICRR) and Sld7 (MTBP) have been identified in metazoans, controversy has surrounded the identity of the Sld2 ortholog. It was originally proposed that the RECQ helicase, RECQL4, which is mutated in Rothmund-Thomson syndrome, represented the closest vertebrate ortholog of Sld2 due to a small region of sequence homology at its N-Terminus...

While basal cell carcinomas (BCCs) arise from ectopic hedgehog pathway activation and can be treated with pathway inhibitors, sporadic BCCs display high resistance rates while tumors arising in Gorlin syndrome patients with germline Patched (PTCH1) mutations are uniformly suppressed by inhibitor therapy. In rare cases, Gorlin syndrome patients on long-term inhibitor therapy will develop individual resistant tumor clones that rapidly progress, but the basis of this resistance remains unstudied. Here we report a case of an SMOi -resistant tumor arising in a Gorlin patient on suppressive SMOi for nearly a decade...

Gorlin-Goltz syndrome (GGS) is an autosomal dominant multisystemic disease with high penetrance. Headache heralding GGS has been previously reported but without discussing potential sources. We report a patient with headache and a novel association (diastematomyelia), which helped with the diagnosis. A 46-year-old woman presented with persistent holocranial headache. On examination, countless hyperpigmented basal cell nevi over the face, pits over the palmar/plantar surface, and palmar and plantar keratosis were observed...

INTRODUCTION: In advanced basal cell carcinoma (BCC), the issue of whether Hedgehog inhibitors (HHIs) should be stopped or not after clinical complete response (cCR) achievement remains an unmet clinical need. MATERIALS AND METHODS: We conducted a retrospective, multicenter study across 7 Italian dermato-oncology units including patients with BCC who continued vismodegib after cCR between 2012 and 2019. We assessed the relationship between the duration of vismodegib intake (days to cCR [DTCR], days to stop after cCR [DTS], total treatment days [TTD]), and disease-free survival (DFS)...