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Gorlin–Goltz syndrome is a rare autosomal dominant disorder caused by an inactivating mutation of the patched 1 gene. Patients could present as early as infancy with varied presentation and multiple basal cell carcinoma. This case report highlights the youngest reported case to date, a 5-month-old patient, who presented with multiple asymptomatic black papules and dysmorphic features. Dermatoscopy and subsequent investigations including targeted gene sequencing confirmed the diagnosis. This case underscores the importance of early recognition and multidisciplinary approach to the management of Gorlin–Goltz syndrome.

Abstract The anomaly known as a bifid rib is difficult to quantify in bioarchaeological collections not only because of its rarity in the population itself (less than 1.5%), but also because of vulnerability to postmortem damage of this part of the skeleton as well as similarity to other developmental anomalies, which can lead to its misidentification. This work presents five cases of rib bifurcation (from four individuals) from four different populations living in Kujawy region in north-central Poland from the Neolithic until the Early Modern Era. Morphological analyses are matched by a paleoradiological investigation. Furthermore, this study endeavours to summarize all known cases of rib bifurcation in archaeological collections and discuss the correctness of the diagnoses. Additionally, criticism of the arguments allegedly proving the presence of naevoid basal cell carcinoma syndrome (NBCCS, Gorlin-Goltz syndrome) in the archaeological populations based on available photographic data of bifurcated ribs and associated anomalies is made. Finally, a new proposal for the classification of this anomaly in osteological material is presented.

Nevoid basal cell carcinoma syndrome is a rare autosomal dominant disorder characterized by a diverse clinical presentation, which includes developmental abnormalities and tumorigenesis that can impact multiple organ systems. Basal cell carcinoma is the most common and characteristic clinical presentation in patients with NBCCS. There are three identified causative genes for this disease, the PTCH1 gene located at 9q22-31, the PTCH2 gene at 1p32-34, and the SUFU gene at 10q24.32. In this paper, we report a case of multiple nevoid basal cell carcinoma. The mutated gene in this patient was determined to be the ELP1 gene located on chromosome 9. This patient's ELP1 gene mutation may contribute to the development of multiple nevoid basal cell carcinomas on the face. [ABSTRACT FROM AUTHOR]

Gorlin–Goltz syndrome is a rare autosomal dominant disorder caused by an inactivating mutation of the patched 1 gene. Patients could present as early as infancy with varied presentation and multiple basal cell carcinoma. This case report highlights the youngest reported case to date, a 5-month-old patient, who presented with multiple asymptomatic black papules and dysmorphic features. Dermatoscopy and subsequent investigations including targeted gene sequencing confirmed the diagnosis. This case underscores the importance of early recognition and multidisciplinary approach to the management of Gorlin–Goltz syndrome. [ABSTRACT FROM AUTHOR]

Treatment with Hedgehog Inhibitors in Gorlin‐Goltz syndrome (GGS) yields favourable objective clinical responses, yet secondary resistance and class‐related toxicity restrict treatment duration. This study aims to review current data on GGS patients undergoing vismodegib therapy, focusing on treatment duration, clinical outcomes and schedule modifications. A systematic search of the PubMed database was conducted for English articles from 1993 to 2023, identifying 31 papers suitable for inclusion. A total of 351 patients, with a mean age of 52 years, were analysed. The average treatment duration was 9.3 months for patients who discontinued treatment, and 25.1 months for those who continued vismodegib at the time this study was published. Vismodegib achieved a complete response rate of 44%. Treatment interruption predominantly occurred due to side effects (69.1%) and secondary resistance (9.1%). The use of alternative regimens, although not compromising efficacy, may enhance treatment compliance. Further investigations are warranted to ascertain the optimal treatment regimen and timeline for GGS patients. Schedule modifications offer promise in ameliorating side effects and facilitating long‐term treatment. [ABSTRACT FROM AUTHOR]

Managing advanced basal cell carcinoma (BCC) in patients with Gorlin-Goltz syndrome presents unique clinical challenges due to the tumor's aggressive nature and potential for widespread metastasis. This case study details a sequential treatment regimen for a 68-year-old female patient with an extensive, inoperable BCC. Employing a multimodal approach that integrates radiotherapy, the Hedgehog pathway inhibitor vismodegib, and High-Intensity Focused Ultrasound (HIFU), we demonstrate the potential for nearly complete remission in a patient with advanced BCC. Initial treatment with radiotherapy and vismodegib reduced tumor size significantly, but the largest mass displayed resistance over time, signifying the need for innovative therapies. Subsequent HIFU treatment targeted individual lesions, showcasing a non-invasive method that provided precise treatment while mitigating systemic side effects. The case emphasizes the necessity of continual adaptation in treatment plans to address the development of resistance and underscores the importance of incorporating new technologies and targeted therapies for complex BCC cases. The successful outcome of this integrated strategy suggests a promising direction for future research and highlights the importance of multidisciplinary approaches that tailor treatment to individual patient needs, tumor characteristics, and evolving therapeutic landscapes. [ABSTRACT FROM AUTHOR]

Abstract Background To demonstrate and analyze the 18F-FDG positron emission tomography/computed tomography (PET/CT) findings in this rare nevoid basal cell carcinoma syndrome (NBCCS). Case presentation A 71-year-old woman with the left invasive breast cancer was treated with hormone therapy for six months and underwent the 18F-FDG PET/CT examination for efficacy evaluation. 18F-FDG PET/CT revealed the improvement after treatment and other unexpected findings, including multiple nodules on the skin with 18F-FDG uptake, bone expansion of cystic lesions in the bilateral ribs, ectopic calcifications and dilated right ureter. She had no known family history. Then, the patient underwent surgical excision of the all skin nodules and the postoperative pathology were multiple basal cell carcinomas. Finally, the comprehensive diagnosis of NBCCS was made. The patient was still in follow-up. Additionally, we have summarized the reported cases (n = 3) with 18F-FDG PET/CT from the literature. Conclusions It is important to recognize this syndrome on 18F-FDG PET/CT because of different diagnoses and therapeutic consequences.

Introduction: Although numerous syndromic and non-syndromic odontogenic lesions of the jaws have been documented in the literature, there are very few cases of simultaneous benign and malignant jaw lesions. Patient Concerns: We present a case of right maxillary squamous cell carcinoma along with several benign odontogenic cystic lesions of the jaws and skeletal abnormalities that meet the criteria for Gorlin-Goltz syndrome. Take-Away Lessons: With a review of the literature, the specifics of management and follow-up are discussed.

Background: To demonstrate and analyze the 18F-FDG positron emission tomography/computed tomography (PET/CT) findings in this rare nevoid basal cell carcinoma syndrome (NBCCS). Case presentation: A 71-year-old woman with the left invasive breast cancer was treated with hormone therapy for six months and underwent the 18F-FDG PET/CT examination for efficacy evaluation. 18F-FDG PET/CT revealed the improvement after treatment and other unexpected findings, including multiple nodules on the skin with 18F-FDG uptake, bone expansion of cystic lesions in the bilateral ribs, ectopic calcifications and dilated right ureter. She had no known family history. Then, the patient underwent surgical excision of the all skin nodules and the postoperative pathology were multiple basal cell carcinomas. Finally, the comprehensive diagnosis of NBCCS was made. The patient was still in follow-up. Additionally, we have summarized the reported cases (n = 3) with 18F-FDG PET/CT from the literature. Conclusions: It is important to recognize this syndrome on 18F-FDG PET/CT because of different diagnoses and therapeutic consequences. [ABSTRACT FROM AUTHOR]

Promising research results have been obtained on the tissue-regeneration properties of PRF (platelet-rich fibrin) in dentistry and maxillofacial surgery. PRF presumably promotes healing and accelerates ossification. In this case report, the patient had a history of Gorlin–Goltz syndrome, also called nevoid basal cell carcinoma syndrome, an autosomal dominant neurocutaneous disease that was known for many years. As a consequence, cysts were detected in both the mandible and maxilla. We performed decompression on this 37-year-old patient, followed by a cystectomy on an extensive lesion in the right angle of the mandible. One cyst from each side of the body mandible and one from the maxilla were completely enucleated, as determined using an intraoral exploration. The resulting bone defect was filled with a composite graft composed of a mixture of A-PRF and a serum albumin-coated bone allograft (BoneAlbumin). The wound was then covered with a PRF membrane. The surgical sites were closed per primam. The postoperative period was uneventful. Biopsies were performed after three and six months of healing for histological micromorphometry analyses. Dental implants were placed at the sampling site. Three months after the implantation, the ossified implants were fitted with superstructures. To date, no complications have appeared with the bone augmentation. The authors interpret from the findings that the combination of A-PRF and BoneAlbumin can be validated as a prosperous bone substitute. It can be safely implanted after a 3-month ossification period. [ABSTRACT FROM AUTHOR]

Managing advanced basal cell carcinoma (BCC) in patients with Gorlin-Goltz syndrome presents unique clinical challenges due to the tumor’s aggressive nature and potential for widespread metastasis. This case study details a sequential treatment regimen for a 68-year-old female patient with an extensive, inoperable BCC. Employing a multimodal approach that integrates radiotherapy, the Hedgehog pathway inhibitor vismodegib, and High-Intensity Focused Ultrasound (HIFU), we demonstrate the potential for nearly complete remission in a patient with advanced BCC. Initial treatment with radiotherapy and vismodegib reduced tumor size significantly, but the largest mass displayed resistance over time, signifying the need for innovative therapies. Subsequent HIFU treatment targeted individual lesions, showcasing a non-invasive method that provided precise treatment while mitigating systemic side effects. The case emphasizes the necessity of continual adaptation in treatment plans to address the development of resistance and underscores the importance of incorporating new technologies and targeted therapies for complex BCC cases. The successful outcome of this integrated strategy suggests a promising direction for future research and highlights the importance of multidisciplinary approaches that tailor treatment to individual patient needs, tumor characteristics, and evolving therapeutic landscapes.

Hybrid odontogenic lesions combine characteristics of two or more lesions in a single site, and are considered a rare condition. The occurrence of this lesion in a patient with Gorlin-Goltz syndrome is even less common. Since the condition has variable clinical aspects and multiple imaging characteristics, histopathological examination is important for the definitive diagnosis of the lesion. This article reports the case of a patient with Gorlin-Goltz syndrome, with multiple odontogenic keratocysts in the mandible and maxilla and presence of an ameloblastoma and keratocyst hybrid odontogenic lesion. Distinct areas with histological patterns characteristic of the cyst and tumor were observed in the same lesion. This unusual but still possible diagnosis should be considered by pathologists and oral-maxillofacial surgeons in the evaluation, diagnosis and treatment of patients with syndromes characterized by odontogenic lesions.

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. [ABSTRACT FROM AUTHOR]

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. Patients with naevoid basal cell carcinoma syndrome (NBCCS) were evaluated separately. Results: We included 38 and 13 patients in the non-syndromic and syndromic OKC groups, respectively. The recurrence rates were 15.8 and 21.4% in the non-syndromic and syndromic groups, respectively; 8.9% of patients exhibited a second recurrence and 1.8% a third recurrence. No second primary OKCs were observed in the non-syndromic group; 76.9% of patients in the syndromic group developed at least one. Conclusion: We found a higher recurrence rate in patients with NBCCS compared with patients with non-syndromic OKCs (21.4 versus 15.8%). The probability of developing a second primary OKC in patients with NBCCS was higher compared with that in patients with non-syndromic OKCs (76.9 versus 0%). No statistically significant risk factors for OKC recurrence were identified. [ABSTRACT FROM AUTHOR]

Gorlin-Goltz syndrome or basal cell nevi syndrome is an ectodermal neoplasia of autosomal dominant inheritance. It is a multisystem disease with a prevalence of 1 case per 57 000 to 150 000 people. It predominates in patients between the second and third decade of life, with a predilection for the male sex., Iit's characterized by the presence of multiple basal cell nevus carcinomas, development of odontogenic keratocystic and palmo-plantar pits or dimples and calcification of the falx brain. Odontogenic keratocysts (OKC) occur in more than 80% of cases of patients with Gorlin-Goltz syndrome (GGS). OKC can present as the first sign of GGS. Approximately 65% of cases affect the mandible, with high frequency in the molar and ramus region. A clinical case is presented of a 35-year-old male patient with a current condition of missing teeth. Physical examination revealed syndromic facies. Orthopantomography is requested, observing multiple radiolucent areas of various sizes as well as retained dental organs, so vacuum puncture and incisional biopsy were taken.; Histopathological result: odontogenic keratocyst and suspicion of GGS because the patient meets the major and minor criteria; complementary studies were requested to confirm the diagnosis. Enucleation of cystic lesions with peripheral ostectomy, extraction of retained and excision of the skin lesion was performed under general anesthesia. After one year, the healing process and bone regeneration was observed without signs of recurrence. The patient was kept under control and monitored by our service with annual appointments. [ABSTRACT FROM AUTHOR]

Introduction: Gorlin-Goltz syndrome also known as Nevoid Basal Cell Carcinoma Syndrome is a rare phakomatoses inherited as an autosomal dominant disorder characterized by mutations of PTCH-1 gene along with microdeletion of chromosome 9q. It is manifested by multiple tumours and abnormalities most importantly featured with multiple basal cell carcinoma, Odontogenic Keratocyst (OKC) and other skeletal disorders. Case Report: A 11- year-old girl having facial asymmetry and pain on the right side of the jaw reported to the department. Radiographic examination revealed multiple radiolucencies in the mandible. The biopsy and histopathological examination confirmed the presence of multiple OKC. Further investigations led to the case fulfilling 3 major criteria of multiple OKC, falx and tentorium cerebelli calcifications, palmar and plantar pits which established the diagnosis of Gorlin-Goltz syndrome. Conclusion: Being a condition requiring a multidisciplinary approach, early diagnosis and appropriate prophylactic measures along with proper treatment is essential for a better prognosis. [ABSTRACT FROM AUTHOR]

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.3512_3526del (p.1171_1176del)] was identified by WES and further validated by Sanger sequencing. Bioinformatic and conformational analysis showed that the mutation caused altered PTCH1 protein structure, which may be related to functional abnormalities. Conclusion: This study expands the mutation spectrum of PTCH1 in GS and facilitates the early diagnosis and screening of GS. PTCH1 [c.3512_3526del (p.1171_1176del)] may cause structural abnormalities and functional disabilities, leading to GS in families. [ABSTRACT FROM AUTHOR]

Abstract Primary cardiac tumors in children are very rare and may be associated with severe arrhythmias and sudden infant death syndrome. These cardiac arrhythmias vary depending on the location and size of the tumor. Sixty-four percent of children with cardiac fibroma, the second most common benign cardiac tumor in children, have ventricular arrhythmias, affecting therapeutic management and risk profile of these children. We report on two siblings with cardiac fibromas whose clinical presentations differed depending on their locations and size of the tumors. The first child, a three-year-old girl, was diagnosed with a cardiac fibroma in the left ventricle at the age of 8 months after surviving resuscitation due to ventricular fibrillation. Secondary prophylactic implantation of an ICD was performed. On propranolol, no further malignant arrhythmias have occurred to date. The seven-month-old brother was diagnosed postnatally with a cardiac tumor adjacent to the right ventricle. A few weeks after birth, the boy had refractory supraventricular tachycardia and ventricular arrhythmia that only resolved with amiodarone. In genetic testing, Gorlin–Goltz syndrome was diagnosed in both children. Conservative pharmacological therapy is a therapeutic strategy for asymptomatic patients with cardiac fibromas. The anti-arrhythmic medication depends on the location of the tumor. Implantation of an ICD should be performed in cases of malignant arrhythmias. In rare cases, there is an association between cardiac tumors and genetic syndromes, such as Gorlin–Goltz syndrome. These should always be considered when such a tumor is diagnosed.

Gorlin–Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is an autosomal dominant disease characterized by multisystemic developmental defects caused by pathogenic variants such as patched-1 (PTCH1) gene variants and/or SUFU gene variants. The presence of either two main criteria or one major and two minor criteria are required for the diagnosis of Gorlin–Goltz syndrome. Recently, a major criterion for molecular confirmation has also been proposed. In this article, we report the case of an 80-year-old male who was admitted at our department for multiple brown-to-black papules and plaques on the entire body. He was diagnosed with Gorlin–Goltz syndrome with clinical, radiologic, and pathologic findings. While the diagnosis was made based on the clinical findings in general, confirmation of the genetic variants makes an ideal diagnosis and suggests a new treatment method for target therapy. We requested a genetic test of PTCH1 to ideally identify the molecular confirmation in the hedgehog signaling pathway. However, no pathogenic variants were found in the coding region of PTCH1, and no molecular confirmation was achieved.

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. A magnetic resonance imaging (MRI) of the spinal cord revealed diastematomyelia. Diagnosis of GGS was finally made. Headache and diastematomyelia should be included in the clinical picture of GGS. [ABSTRACT FROM AUTHOR]

Basal cell nevus syndrome is a genetically linked multisystem disorder with a hallmark tendency for development of multiple basal cell carcinomas at a young age. It is associated with a multitude of other anomalies including keratocytes of the jaw, palmar or plantar pits, and ectopic intracranial calcifications. This disease is most commonly caused by loss of function in tumor suppressor gene PTCH1 resulting in overactivation of the Hedgehog pathway and basal cell carcinoma formation. Diagnosis is largely clinical; patients must meet criteria of both major and minor categories. Genetic testing is warranted in specific situations where clinical diagnosis is unclear or for genetic counseling purposes. Given that basal cell carcinoma is a very common dermatologic disorder, it is important to recognize when it arises in the setting of genetically associated diseases. Early detection allows for proper management and surveillance of not only basal cell carcinomas but also the other multisystem effects of basal cell nevus syndrome. This review gives an in-depth overview of the etiology, pathogenesis, diagnosis, and management of basal cell nevus syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Hybrid odontogenic lesions combine characteristics of two or more lesions in a single site, and they are considered a rare condition. The occurrence of these lesions in patients with Gorlin-Goltz syndrome is even less common. Since the lesion has variable clinical aspects and multiple imaging characteristics, histopathological examination is mandatory for a definitive diagnosis. Methods: This article reports the case of a patient with Gorlin-Goltz syndrome, who had multiple odontogenic keratocysts in the mandible and maxilla, as well as a combined/hybrid ameloblastoma and odontogenic keratocyst lesion. Results: Distinct areas with histological patterns characteristic of the cyst and tumor were observed within the same lesion. Conclusion: This unusual but still possible diagnosis should be considered by pathologists and oral and maxillofacial surgeons when evaluating, diagnosing and treating patients with syndromes characterized by odontogenic lesions. [ABSTRACT FROM AUTHOR]

Introduction: Although numerous syndromic and non-syndromic odontogenic lesions of the jaws have been documented in the literature, there are very few cases of simultaneous benign and malignant jaw lesions. Patient Concerns: We present a case of right maxillary squamous cell carcinoma along with several benign odontogenic cystic lesions of the jaws and skeletal abnormalities that meet the criteria for Gorlin-Goltz syndrome. Take-Away Lessons: With a review of the literature, the specifics of management and follow-up are discussed. [ABSTRACT FROM AUTHOR]

Keratocyst is a developmental odontogenic cyst arising from remnants/rests of the dental lamina with biologic behavior similar to benign neoplasm. The presence of multiple odontogenic keratocysts is rare and seen in Gorlin-Goltz syndrome (GGS). GGS syndrome presents with multisystem involvement and the classical triad of multiple basocellular epitheliomas, keratocysts in the jaws, and bifid ribs; that characterize the diagnosis of this syndrome. Multiple odontogenic keratocyst are the most consistent features of the syndrome in 65%–100% of affected individuals and are generally diagnosed at a very early age. Early diagnosis and proper counseling of the parent and patient might help to reduce the morbidity, encourage follow-up for timely treatment, and help in avoiding ionizing radiation that would lead to the development of malignancies. [ABSTRACT FROM AUTHOR]

Keratocyst is a developmental odontogenic cyst arising from remnants/rests of the dental lamina with biologic behavior similar to benign neoplasm. The presence of multiple odontogenic keratocysts is rare and seen in Gorlin-Goltz syndrome (GGS). GGS syndrome presents with multisystem involvement and the classical triad of multiple basocellular epitheliomas, keratocysts in the jaws, and bifid ribs; that characterize the diagnosis of this syndrome. Multiple odontogenic keratocyst are the most consistent features of the syndrome in 65%–100% of affected individuals and are generally diagnosed at a very early age. Early diagnosis and proper counseling of the parent and patient might help to reduce the morbidity, encourage follow-up for timely treatment, and help in avoiding ionizing radiation that would lead to the development of malignancies.

Gorlin–Goltz syndrome (basal cell nevus syndromes) is an uncommon, autosomal dominant inherited disorder characterized by developing basal cell carcinomas from a young age. Other distinct clinical features include keratocystic odontogenic tumors, dyskeratotic palmar and plantar pitting, and skeletal abnormalities. Clinicopathological findings of the syndrome are very diverse, and many symptoms manifest during a certain period of life. We present the compelling whole-body bone scan and 18F-FDG PET/CT findings in a 32-year-old man with odontogenic keratocyst, early-onset basal cell carcinoma, multiple ectopic calcifications in extremities, calcified falx cerebri, spinal scoliosis, macrocephaly, and ocular hypertelorism. [ABSTRACT FROM AUTHOR]

Gorlin–Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is an autosomal dominant disease characterized by multisystemic developmental defects caused by pathogenic variants such as patched-1 (PTCH1) gene variants and/or SUFU gene variants. The presence of either two main criteria or one major and two minor criteria are required for the diagnosis of Gorlin–Goltz syndrome. Recently, a major criterion for molecular confirmation has also been proposed. In this article, we report the case of an 80-year-old male who was admitted at our department for multiple brown-to-black papules and plaques on the entire body. He was diagnosed with Gorlin–Goltz syndrome with clinical, radiologic, and pathologic findings. While the diagnosis was made based on the clinical findings in general, confirmation of the genetic variants makes an ideal diagnosis and suggests a new treatment method for target therapy. We requested a genetic test of PTCH1 to ideally identify the molecular confirmation in the hedgehog signaling pathway. However, no pathogenic variants were found in the coding region of PTCH1, and no molecular confirmation was achieved. [ABSTRACT FROM AUTHOR]

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Abstract Background Gorlin-Goltz syndrome (GS) is an inherited disease characterized by predisposition to basal cell carcinomas (BCCs) and various developmental defects, whose numerous disease-causing PTCH1 mutations have been identified in the hedgehog (Hh) signaling pathway. Methods In this study, whole exome sequencing was used to screen for both somatic and germline deleterious mutations in three sisters with a lethal GS. The mutations we found were confirmed by subcloning and Sanger sequencing of the genomic DNA. RNA-seq was performed to profile gene expression in paired BCCs samples and the expression levels for selected genes were validated by quantitative PCR. Results The clinical and histopathologic features were analyzed for the proband in the three-generation GS family. We identified the insertion mutation PTCH1 c.1341dupA (p. L448Tfs*49), which segregated with BCC phenotype and contributed to the death of two in four patients from a Chinese family with GS. Compared with adjacent non-cancerous tissues (ANCT), four second-hit mutations were found in four of the six pairs of BCC from three patients. Of note, somatic genomic alterations in all six BCC samples were mainly clustered into non-clock-like Signature 7 (ultraviolet mutagenesis) and 11 (related to certain alkylating agents). Both RNA-seq and quantitative RT-PCR confirmed that the mRNA levels of PTCH1 and its effector GLI1 were markedly upregulated in six pairs of BCC samples versus ANCT. Conclusions The distinct non-clock-like signatures of BCCs indicated that GS was not a life-threatening illness. The main reasons for untimely death of GS patients were PTCH1 mutation, exposure to intense ultraviolet radiationand the poor economic conditions.

Abstract Background Gorlin syndrome, also known as Gorlin-Goltz syndrome (GGS) or basal cell nevus syndrome (BCNS) or nevoid basal cell carcinoma syndrome (NBCCS), is an autosomal dominant familial cancer syndrome. It is characterized by the presence of numerous basal cell carcinomas (BCCs), along with skeletal, ophthalmic, and neurological abnormalities. It is essential to anticipate the diagnosis by identifying the pathology through the available diagnostic tests, clinical signs, and radiological manifestations, setting up an adequate treatment plan. Main body In the first part, we searched recent databases including MEDLINE (PubMed), Embase, and the Cochrane Library by analyzing the etiopathogenesis of the disease, identifying the genetic alterations underlying them. Subsequently, we defined what are, to date, the major and minor clinical diagnostic criteria, the possible genetic tests to be performed, and the pathologies with which to perform differential diagnosis. The radiological investigations were reviewed based on the most recent literature, and in the second part, we performed a review regarding the existing jawbone protocols, treating simple enucleation, enucleation with bone curettage in association or not with topical use of cytotoxic chemicals, and “en bloc” resection followed by possible bone reconstruction, marsupialization, decompression, and cryotherapy. Conclusion To promote the most efficient and accurate management of GGS, this article summarizes the clinical features of the disease, pathogenesis, diagnostic criteria, differential diagnosis, and surgical protocols. To arrive at an early diagnosis of the syndrome, it would be advisable to perform radiographic and clinical examinations from the young age of the patient. The management of the patient with GGS requires a multidisciplinary approach ensuring an adequate quality of life and effective treatment of symptoms.

Rationale: Gorlin‑Goltz syndrome (GGS) has a wide range of expressivity, with a majority of cases being first diagnosed from the oral findings. Early intervention can reduce its severity. Patient Concerns: The primary complaints of all the patients were pain and swelling. Clinical examination with radiological and histopathological evaluation confirmed the diagnosis. Diagnosis: This series presents the six cases of GGS treated over a time frame of five years (2018–2022). Treatment: The treatments range from enucleation, chemical cauterisation and peripheral ostectomy to aggressive modalities such as resection and reconstruction. Outcomes: This series comprises of six patients with ages ranging from 12 to 42 years, four of which were female and two were male presenting minimal expression to highly aggressive forms and its unpredictable frequent manifestation. Take-Away Lessons: This emphasises the significance of long‑term periodic follow‑up and genetic screening for early detection, thereby reducing the intensity and aggressiveness of the disease. [ABSTRACT FROM AUTHOR]

The odontogenic keratocyst (OKC) belongs to the developmental cysts of the jawbones and constitutes either a solitary pathological condition (sporadic OKC) or a manifestation of a syndrome (syndromic OKC), most commonly of the Gorlin-Goltz syndrome. The aim of this study is to review the pertinent literature on the sporadic OKC, focusing on the current views regarding its pathogenesis. OKC is the third most common odontogenic cyst, following the radicular cyst and the dentigerous cyst. It shows no gender predilection and is usually diagnosed in patients in their 4th decade of life. It is usually asymptomatic and is most often an incidental radiographic finding, usually presenting as a unilocular radiolucent lesion with clear borders. The pathognomonic histopathological features of OKC include palisaded basal cells with reverse polarization of their hyperchromatic nuclei, and the parakeratinization of the superficial epithelial layer. Both the cystic epithelium and the cystic wall play a pivotal role in the pathogenesis of OKC, while the epithelial-mesenchymal interaction promotes the expression of pro-inflammatory molecules and induces osteolytic mechanisms, with the participation of various signaling pathways, such as SHH, WNT, ERK/MAPK and PI3K, and epigenetic mechanisms. The treatment of choice for OKC is surgical therapy, while regular x-ray examinations at least until the first two decades after the diagnosis are recommended for the early identification of recurrences. [ABSTRACT FROM AUTHOR]

Purpose: To answer the following clinical research question: "Among patients with multiple basal cell carcinomas (mBCCs), can panoramic radiograph (PaR) facilitate the diagnosis of Gorlin-Goltz syndrome (GGS)?" Methods: This retrospective study enrolled mBCCs subjects who presented to a German tertiary care center between 1 January 2015 and 31 December 2021. The primary predictor was presence of syndromic mBCCs, and the main outcomes were jaw cysts and odontogenic keratocysts (OKCs). Descriptive, bi- and multivariate statistics, diagnostic test evaluation, and number needed to screen (NNS) were computed at α = 95%. Results: The sample comprised 527 mBCCs patients (36.1% females; 6.8% GGS; 5.5% OKCs; mean age, 74.5 ± 15.8 years [range, 15-102]). There was a significant association between syndromic mBCCs and jaw cysts (P <.0001; NNS = 2 [95% CI, CI, 1.1 to 1.4]). In the adjusted logistic model, PaR identified GGS via radiographic diagnosis of jaw cysts in case of 1) age ≤ 35 years, 2) ≥ 5 BCCs, and 3) ≥ 1 high-risk BCCs. Nearly every jaw cyst identified by PaR was OKCs (P =.01; 95% CI, 3.1 to 3,101.4; NNS = 1.3 [95% CI,.9 to 2]). The post hoc power was 100%. Conclusions: Dental screening with the use of PaR for mBCCs patients, especially those aged ≤35 years, or with ≥5 BCCs, or ≥1 high-risk BCCs, may be helpful in detection and identification of GGS through recognition of OKCs. [ABSTRACT FROM AUTHOR]

Background: Congenital medulloblastoma is very rare, and many cases involve germline mutations that can lead to inherited syndromes. Here, we first report two brothers with congenital medulloblastoma who were diagnosed with Gorlin-Goltz syndrome caused by SUFU mutation. Clinical presentation: Medulloblastoma was detected in two brothers at 2 and 3 months of age, with very similar imaging features. Genetic testing revealed that both children and their mother carried SUFU gene germline mutations, and both brothers were diagnosed with Gorlin-Goltz syndrome. Conclusion: Gorlin-Goltz syndrome-associated congenital medulloblastoma with SUFU germline mutation is very rare. Pathological types mostly involve desmoplastic/nodular or extensive nodularity; chemotherapy is the main treatment, and studies revealing prognostic data are scarce. [ABSTRACT FROM AUTHOR]

Background: Ovarian sex cord‐stromal tumors (OSCTs) are rare ovarian tumors that can develop from sex cord, stromal cells, or both. OSCTs can be benign or malignant. Bilateral and/or unilateral ovarian fibromas, a type of OSCT of the stromal cells, have been reported in individuals diagnosed with nevoid basal cell carcinoma syndrome (NBCCS). Calcified ovarian fibromas have been reported in 15–25% of individuals diagnosed with NBCCS while 75% of those cases occur bilaterally. The average age at diagnosis of OSCT/ovarian fibromas in patients with NBCSS is in the second to third decade compared with age 50 in the general population. Ovarian tumors are rare in pediatric populations. Methods: The patient is a 5‐year‐old female diagnosed with bilateral ovarian fibromas at age 4. Multigene panel for the patient and subsequent targeted molecular evaluation of parents were completed. Histological evaluations on the surgically resected ovaries were performed for microscopic characterization of fibromas. Results: Germline testing identified de novo heterozygous novel likely pathogenic variants in PTCH1 gene, exon 12 deletion, and an SMARCA4 splicing variant c.2002‐1G > A. Microscopic examination of bilateral tumors was consistent with an ovarian fibroma. Conclusions: To our knowledge, this is the first report of bilateral benign ovarian fibroma in a child with a diagnosis of nevoid basal cell carcinoma syndrome (NBCCS) with a potential predisposition to Rhabdoid Tumor Predisposition Syndrome (RTPS). [ABSTRACT FROM AUTHOR]

BackgroundCongenital medulloblastoma is very rare, and many cases involve germline mutations that can lead to inherited syndromes. Here, we first report two brothers with congenital medulloblastoma who were diagnosed with Gorlin-Goltz syndrome caused by SUFU mutation.Clinical presentationMedulloblastoma was detected in two brothers at 2 and 3 months of age, with very similar imaging features. Genetic testing revealed that both children and their mother carried SUFU gene germline mutations, and both brothers were diagnosed with Gorlin-Goltz syndrome.ConclusionGorlin-Goltz syndrome-associated congenital medulloblastoma with SUFU germline mutation is very rare. Pathological types mostly involve desmoplastic/nodular or extensive nodularity; chemotherapy is the main treatment, and studies revealing prognostic data are scarce.

Background: Gorlin-Goltz syndrome (GS) is an inherited disease characterized by predisposition to basal cell carcinomas (BCCs) and various developmental defects, whose numerous disease-causing PTCH1 mutations have been identified in the hedgehog (Hh) signaling pathway. Methods: In this study, whole exome sequencing was used to screen for both somatic and germline deleterious mutations in three sisters with a lethal GS. The mutations we found were confirmed by subcloning and Sanger sequencing of the genomic DNA. RNA-seq was performed to profile gene expression in paired BCCs samples and the expression levels for selected genes were validated by quantitative PCR. Results: The clinical and histopathologic features were analyzed for the proband in the three-generation GS family. We identified the insertion mutation PTCH1 c.1341dupA (p. L448Tfs*49), which segregated with BCC phenotype and contributed to the death of two in four patients from a Chinese family with GS. Compared with adjacent non-cancerous tissues (ANCT), four second-hit mutations were found in four of the six pairs of BCC from three patients. Of note, somatic genomic alterations in all six BCC samples were mainly clustered into non-clock-like Signature 7 (ultraviolet mutagenesis) and 11 (related to certain alkylating agents). Both RNA-seq and quantitative RT-PCR confirmed that the mRNA levels of PTCH1 and its effector GLI1 were markedly upregulated in six pairs of BCC samples versus ANCT. Conclusions: The distinct non-clock-like signatures of BCCs indicated that GS was not a life-threatening illness. The main reasons for untimely death of GS patients were PTCH1 mutation, exposure to intense ultraviolet radiationand the poor economic conditions. [ABSTRACT FROM AUTHOR]

Gorlin-Goltz syndrome is a rare autosomal dominant disease characterized by odontogenic keratocysts and basal cell carcinoma as well as ophthalmic and neurological implications. The following article presents the case of a 20-year-old female with Gorlin-Goltz syndrome incidentally found to have a cardiac mass. An ECG showed diffuse T-wave inversions in the lateral leads despite a lack of any acute coronary symptoms in the patient. Echocardiogram, cardiac MRI and CT scan confirmed a nonvascularized, smoothly marginated mass arising from the left ventricular apex without any hemodynamic compromise. A whole-body PET scan further demonstrated localized hyperactivity associated with a cardiac fibroma without any evidence of metastasis. The cardiac fibroma was surgically excised for definitive management to prevent the possibility of sudden cardiac death and congestive heart failure. [ABSTRACT FROM AUTHOR]