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Importance: Germline SUFU pathogenic variants (PVs) have previously been associated with basal cell nevus syndrome (BCNS) and multiple infundibulocystic basal cell carcinoma syndrome; however, a broader spectrum of cutaneous findings in patients with SUFU PVs has not been well delineated., Objective: To define the clinical and histopathologic spectrum of cutaneous findings in patients with germline SUFU PVs., Design, Setting, and Participants: This case series was conducted in multiple US academic dermatology, medical genetics, and medical oncology clinics between July 2014 and July 2022. The study included patients with confirmed germline SUFU PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023., Main Outcomes and Measures: Histopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens., Results: All 5 patients were women. The mean (range) age at presentation was 50.2 (31-68) years, with skin manifestations initially appearing in the fourth to sixth decades of life. None had keratocystic odontogenic tumors. A total of 29 skin pathology specimens from the 5 patients were reviewed; of these, 3 (10.3%) were diagnosed as basaloid follicular hamartomas (BFHs), 10 (34.5%) classified as infundibulocystic basal cell carcinomas (iBCCs), 6 (20.7%) classified as nodular basal cell carcinomas (nBCCs), and 1 (3.4%) as infiltrative basal cell carcinoma (BCC). Targeted NGS studies on tumor specimens suggest that an increased number of UV-signature variants is associated with basal cell carcinomas compared with more indolent basaloid follicular hamartomas., Conclusions and Relevance: Patients with germline SUFU PVs may present with multiple indolent basaloid neoplasms in addition to conventional basal cell carcinomas, typically appearing in the fourth to sixth decades of life. Although there are overlapping clinical manifestations, these findings help to differentiate the clinical syndrome associated with SUFU PVs from PTCH1 BCNS. Awareness of the clinicopathologic spectrum of SUFU-associated basaloid neoplasms is important for dermatologists and dermatopathologists because many (although not all) of these lesions are indolent and do not require aggressive surgical treatment. Importantly, because SUFU lies downstream of the protein smoothened, vismodegib and other smoothened inhibitors are unlikely to be effective therapies in this subset of patients.

Gorlin syndrome can be caused by pathogenic/likely pathogenic (P/LP) variants in the tumor suppressor gene PTCH1 (9q22.1-q31), which encodes the receptor for the sonic hedgehog (SHH) ligand. We present a 12-month-old boy clinically diagnosed with Gorlin syndrome who was found to have significantly delayed development, palmar pitting, palmar and plantar keratosis, short hands, frontal bossing, coarse face, hypertelorism, a bifid rib, misaligned and missing teeth, and SHH-activated medulloblastoma. Genetic testing, including a pediatric cancer panel and genome sequencing with peripheral blood, failed to identify any P/LP variants in PTCH1. Paired tumor/normal exome sequencing was performed, which identified a germline NM_000264.5 (PTCH1): c.361_362ins? alteration through manual review of sequencing reads. Clinical RNA sequencing further demonstrated an Alu insertion at this region (PTCH1: c.361_362insAlu), providing molecular confirmation of Gorlin syndrome. This finding exemplifies a unique mechanism for PTCH1 disruption in the germline and highlights the importance of comprehensive analysis, including manual review of DNA sequencing reads and the utility of RNA analysis to detect variant types which may not be identified by routine genetic screening techniques., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Gorlin-Goltz syndrome, also known as basal cell nevus syndrome, is a rare condition characterised by skeletal abnormalities, odontogenic keratocysts and basal cell nevi. Diagnosis of this condition is based on major and minor clinical and radiological criteria. Oral medicine and radiology specialists are crucial in diagnosing this condition due to the oral and maxillofacial symptoms. However, conventional radiographs may not provide enough information for an accurate diagnosis, including the two-dimensional imaging modalities. Therefore, the importance of advanced digital imaging for diagnosis is highlighted in this case report of a male patient in his late 20s. The patient had missing teeth and asymptomatic multiple swelling in the orofacial region for 2 months. Routine clinical examination, radiographic investigations and histopathological evaluation led to incidental finding of multiple cystic lesions in the maxillary and mandibular region which on further evaluation led to the final diagnosis of Gorlin-Goltz syndrome., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To demonstrate and analyze the 18 F-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 18 F-FDG PET/CT examination for efficacy evaluation. 18 F-FDG PET/CT revealed the improvement after treatment and other unexpected findings, including multiple nodules on the skin with 18 F-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 18 F-FDG PET/CT from the literature., Conclusions: It is important to recognize this syndrome on 18 F-FDG PET/CT because of different diagnoses and therapeutic consequences., (© 2024. The Author(s).)

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.

Gorlin-Goltz syndrome, also known as Gorlin syndrome, basal cell nevus syndrome, and nevoid basal cell carcinoma syndrome, is an autosomal dominant genetic disorder. Its hallmark is an early onset of basal cell carcinoma. Additionally, the syndrome is characterized by a spectrum of distinct clinical attributes encompassing oral, skeletal, ophthalmic, neurological, and developmental aberrations. This condition arises due to anomalies in the Hedgehog signaling pathway, leading to constant pathway activity and uncontrolled growth of tumor cells. Early identification of the disorder through available diagnostic methods and clinical and radiological findings is crucial for accurate diagnosis, which subsequently leads to the formulation of an effective treatment regimen. The purpose of this case report is to discuss the role of a dentist in early detection based on various author-prescribed criteria and the need for a multidisciplinary approach to the treatment of patients with this syndrome.

Background: Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is a rare autosomal dominantly inherited disorder that is characterized by multisystem disorder such as basal cell carcinomas, keratocystic odontogenic tumors and skeletal abnormalities. Bilateral and/or unilateral ovarian fibromas have been reported in individuals diagnosed with NBCCS., Case Presentation: A 22-year-old female, presented with low back pain, and was found to have bilateral giant adnexal masses on pelvic ultrasonography, which had been suspected to be malignant ovarian tumors. Positron emission tomography/computed tomography showed multiple intracranial calcification and skeletal abnormalities. The left adnexa and right ovarian tumor were resected with laparotomy, and pathology revealed bilateral ovarian fibromas with marked calcification. We recommended the patient to receive genetic testing and dermatological examination. No skin lesion was detected. Germline testing identified pathogenic heterozygous mutation in PTCH1 (Patched1)., Conclusions: The possibility of NBCCS needs to be considered in patients with ovarian fibromas diagnosed in an early age. Skin lesions are not necessary for the diagnosis of NBCCS. Ovarian fibromas are managed with surgical excision with an attempt at preserving ovarian function. Follow-up regime and counseling on options for future fertility should be offered to patients., (© 2023. The Author(s).)

Basal cell nevus syndrome is a rare, autosomal dominant disorder, predominantly caused by a mutation in the PTCH1 gene. As basal cell carcinomas and keratocysts are the most common abnormalities, dermatologists, orofacial maxillary surgeons, and dentists play a key role in patient care. From the age of 8, screening for odontogenic keratocysts with an orthopantomogram or MRI is recommended every other year. The intensity increases to annual screening after the development of the first odontogenic keratocyst. If BCNS is caused by an underlying SUFU mutation, screening is not indicated since there are no reports of odontogenic keratocyst in these patients to date. Radiation exposure by, for example, computed tomography, should be minimized as it induces new BCCs. Regular follow-up by a dermatologist for early diagnosis and treatment of (multiple) BCC's is recommended for life.

Two male patients with bifid rib-basal cell nevus-jaw cyst syndrome (BCNS) were admitted to Department of Stomatology, the First Affiliated Hospital of Bengbu Medical College due to radiological findings of multiple low density shadows in the jaw. Clinical and imaging findings showed thoracic malformation, calcification of the tentorium cerebellum and falx cerebrum as well as widening of the orbital distance. Whole exon high-throughput sequencing was performed in two patients and their family members. The heterozygous mutations of c.C2541C>A(p.Y847X) and c.C1501C>T(p.Q501X) in PTCH1 gene were detected in both patients. Diagnosis of BCNS was confirmed. The heterozygous mutations of PTCH1 gene locus were also found in the mothers of the two probands. Proband 1 showed clinical manifestations of low intelligence, and heterozygous mutations of c.C2141T(p.P714L) and c.G3343A(p.V1115I) were detected in FANCD2 gene. Proband 2 had normal intelligence and no FANCD2 mutation. The fenestration decompression and curettage of jaw cyst were performed in both patients. Regular follow-up showed good bone growth at the original lesion, and no recurrence has been observed so far.

BACKGROUND Gorlin syndrome, also known as basal cell nevus syndrome (BCNS), nevoid basal cell carcinoma syndrome (NBCCS), and Jaw cyst-Basal cell nevus-Bifid rib syndrome, is a rare multisystemic syndrome that can affect a remarkable number of tissues and organs in the human body. Patients with this syndrome are in jeopardy of developing basal cell skin cancer during puberty or early adulthood. CASE REPORT Herein, we report a case of a 58-year-old woman who had multiple pigmented skin lesions and a palpable tumor of the left scapula. The patient underwent surgical excision of the above-mentioned lesions. The histopathological examination revealed that 10 of them were basal cell skin carcinomas (BCCs); therefore, the patient was proven to have the syndrome. She had a history of similar skin lesions, which were removed before the age of 20. CONCLUSIONS This case highlights that rare phenomena, such as the presence of multiple BCCs, require additional investigations and a multidisciplinary approach since a rare and potentially life-threating condition might be the underlying cause. Early diagnosis of Gorlin syndrome is of paramount importance to facilitate the appropriate therapeutic approach, as directed by a multidisciplinary team. Patients with multiple skin lesions need to have regular assessments by their general practitioner or dermatologist, with dermoscopy serving as an important preventive measure. Furthermore, because pathogenesis of the syndrome is characterized by development of basal cell carcinomas, consecutive follow-up is of a great significance.

Gorlin syndrome is a rare autosomal dominant disease caused by mutations in the PTCH1, PTCH2, and SUFU genes. Each symptom of the disease has a different time point of onset, which makes early diagnosis based solely on symptoms challenging. In this study, a gene panel was developed to overcome the challenges in the diagnosis of Gorlin syndrome and allow diagnosis using a single test. A custom panel was generated for four genes associated with Gorlin syndrome: PTCH1, PTCH2, SMO, and SUFU. Twenty-seven samples from 12 patients with Gorlin syndrome and three asymptomatic blood relatives of the patients were examined. This panel was highly reliable with a high Q30 quality score, on-target ratio, and coverage. The panel was time- and cost-efficient and enabled the detection of more mutations than whole-exome sequencing for the same patient. Pathogenic mutations in both PTCH1 and PTCH2 were detected in five of the 12 patients with Gorlin syndrome who were diagnosed based on clinical symptoms. Using this panel, the same mutation was identified in the patients and their blood relatives. In summary, this panel facilitated the highly reliable genetic diagnosis of Gorlin syndrome at a low cost, using only blood samples., Competing Interests: Competing interests None., (Copyright © 2022 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

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.

Gorlin syndrome is a rare autosomal dominant disorder with near complete penetrance. The underlying genetic mechanism is a mutation in a tumor suppressor gene. Thus far, mutations in patched homolog 1 and 2 genes (PTCH1 and PTCH2) and the suppressor of fused gene (SUFU) have been identified. The syndrome is characterized by neoplasms arising early in childhood as well as developmental abnormalities, including ophthalmic anomalies. We present the first case associating Gorlin syndrome with a rare retinal lesion known as solitary circumscribed retinal astrocytic proliferation (SCRAP). SCRAP is a benign, stable retinal tumor. For this reason, it is essential to differentiate it from similar retinal lesions that are associated with poor prognosis. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:514-516.] .

The diagnostic trends of Gorlin syndrome (GS) in the pediatric population are not well understood. In an international survey conducted by the Gorlin Syndrome Alliance, 118 individuals who were diagnosed with GS when aged 18 years and under provided information about their diagnosis. Oral surgeons and dermatologists were the most commonly reported physicians involved in diagnosis for 48.3% and 28% of cases, respectively. For 50% of children, the diagnosis was made within a year from presenting sign(s), while 27% report over 4 years to receive GS diagnosis. Of individuals who reported >4 years between presenting signs and diagnosis, 81.3% attributed the delay to insufficient medical team knowledge and 65.6% attributed to lack of personal awareness that presenting signs were related to GS, emphasizing the need for patient and physician education of GS for prompt diagnosis., (© 2022 Wiley Periodicals LLC.)

Abstract: Nevoid basal cell carcinoma syndrome is a rare genetic disorder that has an impact on the body's organs, such as skin and skeletal. Clinical features, physical and pathological examinations, surgical treatment, and diagnostic criteria have been explicated by means of describing the medical experience of a patient with nevoid basal cell carcinoma syndrome in this report., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Basal cell nevus syndrome, also known as Gorlin-Goltz syndrome, is a rare autosomal dominant disorder caused by mutations in the hedgehog signaling pathway, mainly in PTCH1. This pathway is involved in embryogenesis and tumorigenesis, and the loss of function of PTCH1 protein produces an aberrant increase in the hedgehog signaling pathway activity. Basal cell nevus syndrome is characterized by tumor predisposition, particularly with the development of multiple basal cell carcinomas at an early age, along with odontogenic keratocysts, palmoplantar pits, skeletal abnormalities, and an increased risk of medulloblastoma. Diagnosis is clinical, with gene mutation analysis confirming the suspicion. The striking phenotypic variability of the syndrome may lead to a delayed diagnosis, making it an uncommon but important entity to recognize. A high index of suspicion and an early diagnosis is crucial for prevention, surveillance, and the prompt establishment of multidisciplinary medical care., (© 2021 the International Society of Dermatology.)

Purpose: Gorlin syndrome (GS) is a rare genetic disorder characterized by lifetime risk of basal cell carcinomas (BCCs), skeletal anomalies (SAs), and other extracutaneous neoplasms. There is great variation in disease severity, and a genotype-phenotype correlation has not been well established. Here, we investigate whether patients' clinical characteristics predict disease severity to inform clinical decision making., Methods: Data of 248 patients with GS were collected between 2014 and 2021 from three institutions. Multivariable regression analyses were performed to investigate whether clinical characteristics predicted disease burden. Genotype-phenotype correlations were investigated in 40 patients., Results: Patients with SAs had a mean increase of 120 lifetime BCCs (95% CI, 27.1 to 213) relative to patients without SAs. Those with ≥ 2 SAs had 2.45 increased odds (95% CI, 1.01 to 5.91) of advanced or metastatic BCCs. Moreover, the presence of multiple SAs was associated with 5.00 increased odds of having a keratocystic odontogenic tumor (95% CI, 2.22 to 11.3) and 2.79 increased odds of an ovarian fibroma (95% CI, 1.05 to 7.40). Genotype-phenotype analyses showed that missense/in-frame mutations were more likely to be hereditary compared with severe deleterious mutation types (100% v 27%; P = .004). In addition, heat map visualization illustrated that those with more deleterious variants, like large deletions, trended toward increased burden of SAs and BCCs per year., Conclusion: GS patients with SAs may be at greater risk for developing more numerous and severe BCCs and other neoplastic growths including keratocystic odontogenic tumors and ovarian fibromas. Current clinical guidelines suggest yearly follow-up in individuals with GS. Since SAs are usually recognized at the time of diagnosis, our results suggest that more vigilant lifetime multidisciplinary surveillance should be considered for these patients starting in childhood., Competing Interests: Irene Bailey-HealyStock and Other Ownership Interests: Abeona TherapeuticsResearch Funding: Abeona Therapeutics (Inst), Phoenix Tissue Repair (Inst), BioMendics (Inst), Krystal Biotech (Inst), Fibrocell (Inst), Phoenix Tissue Repair (I) Jean Y. TangLeadership: PellePharmStock and Other Ownership Interests: PellePharmHonoraria: Abeona TherapeuticsPatents, Royalties, Other Intellectual Property: I am a cofounder of PellePharm and on the SABTravel, Accommodations, Expenses: PellePharmNo other potential conflicts of interest were reported.

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.

Objectives: Nevoid Basal Cell Carcinoma Syndrome (NBCS) is a rare genetic condition affecting multiple organs including the maxillofacial and dental region. The surgical removal of the odontogenic keratocystic tumors (OKT), the high rate of recurrence leads to a iatrogenic tooth loss requiring dental care. The aim of this study is therefore to describe the dental and orthodontic management, and to assess the impact of surgery on facial growth and oral development., Methods: A retrospective study including 14 patients with GGS, followed at the Necker Enfants Malades Hospital. The study was carried out on the medical files and photographic records RESULTS: Patients developed on average 5.5 OKT (range: 1 to 11) and 1.7 recurrences (range:0 to 9) during the follow-up. The mean age at diagnosis of first OKT was 11.23 years (range: 6.75 to 16). KOTs were more frequently localized at the mandibular (30.9%) and maxillary molar level (25.1%). Forty-seven impacted teeth were extracted during the OKT removal. Eight patients out of 12 presented a class III skeletal relationship. The remaining ones had a skeletal class II associated with a hyperdivergent typology. Almost all patients had dental impactions with ectopic positions of the succedaneums tooth. At the inter-arch level, all patients needed orthodontic care, 3 patients did not begin their orthodontics. Orthodontic treatments began with an orthopedic phase followed by braces for the majority in 8 patients. Two patients had to undergo orthognathic surgery. Impacted teeth were treated by traction or extraction with further rehabilitation., Conclusion: The objective is not to simply compensate the iatrogenic hypodontia generated by the surgical procedure but to take into consideration the maxillofacial phenotype, skeletal characteristics and numerous intra- and inter-arch dental anomalies for a healthy oral management., Competing Interests: Declaration of Competing Interest No conflict of interest., (Copyright © 2021. Published by Elsevier Masson SAS.)

Objectives: To reach a molecular diagnosis for a family with two consecutive fetuses presenting with multiple congenital anomalies., Methods: The two fetuses underwent prenatal ultrasound, autopsy, radiologic, and genetic investigation. Genetic analysis included karyotype and array-CGH for both fetuses and trio-based whole exome sequencing (WES) only for the second fetus., Results: WES results, initially focusing on recessive or dominant de novo variants, were negative.However, as a result of new relevant information regarding family history, the variant c.648&#95;651dup in the PTCH1 gene was identified as causative of the fetal phenotype., Conclusions: This case further highlights how WES data analysis and interpretation strongly rely on family history and robust genotype-phenotype correlation. This is even more relevant in the prenatal setting, where access to fetal phenotype is limited and prenatal recognition of many morbid genes is not fully explored. We also provide a detailed description of the prenatal manifestations of Basal Cell Nevus Syndrome., (© 2022 John Wiley & Sons Ltd.)

We present a case of Gorlin-Goltz syndrome (GGS) in a patient who developed medulloblastoma, osteosarcoma, myelodysplastic syndrome, basal cell carcinoma, and odontogenic keratocyst by the age of 19 years. He had no known family history and no characteristic physical features of GGS. A frameshift mutation in the PTCH1 gene was found in the oral mucosa as a low-frequency mosaicism, basal cell carcinoma, and normal skin by whole exome sequencing of cancer susceptibility genes. Setting a therapeutic strategy with regard to second cancer development is important for pediatric cancer patients who have a background of cancer predisposition. Advances in comprehensive multigenetic analysis are anticipated to aid in developing such a strategy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Nevus-like basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disease characterized by the occurrence of multiple maxillofacial keratocysts, basal cell carcinoma, child medulloblastoma, and various skeletal and soft tissue dysplasia. In 2020, a patient with NBCCS dominated by facial basal cell carcinoma was admitted to Xiangya Hospital of Central South University. The patient was an elderly woman. Ten years ago, the systemic mass appeared, especially on the face, but it was not treated. Later, these masses gradually increased in volume and number, and showed invasive properties. The nasal mass was broken and suppurated, seriously affecting the patient's life quality. The patient came to the hospital to improve the symptoms. Staphylococcus aureus and Providencia rettgeri were cultured in the patient's nasal secretions. Nasal sinus enhanced MRI showed that the subcutaneous soft tissue of the right cheek and the anterolateral mucosa of the left nasal cavity were invaded, indicating multiple malignant skin lesions. After admission, local anesthesia was performed and some masses were removed. Pathological examination of the mass showed basal cell carcinoma. After general anesthesia, multiple masses were resected. The postoperative pathological examination showed that multiple basal cell carcinoma invaded the deep dermis near subcutaneous fat layer. Combined with the results of clinical and immunohistochemical examination, the patient was diagnosed as NBCCS. There were no clear tumor thrombus in the vessel and no nerve invasion. No recurrence or new tumor was found after 1 year follow-up. The incidence rate of NBCCS is low and clinical symptoms are different. The patient's life quality is poor and the patient needs long-term individualized treatment.

Background: Nevoid basal cell carcinoma syndrome (NBCCS) is a rare genetic disorder associated with basal cell carcinomas (BCC), skeletal anomalies, and jaw cysts, and a number of ocular abnormalities. We describe a case of a 12-year-old boy diagnosed with NBCCS found to have several ophthalmic manifestations including a myelinated retinal nerve fiber. We conducted a literature review targeting the ocular and systemic manifestations of NBCCS, with a focus on the ophthalmic findings that have not been well characterized., Materials and Methods: We conducted a literature search from 1960 to 2021 utilizing specific keywords and criteria and excluded non-clinical articles. A total of 46 articles were ultimately used for the literature review., Results: In NBCCS, BCCs typically present before the age of 30 and gradually become numerous. Certain ocular features, less common in the general population, are much more common with NBCCS. Depending on the study, prevalence of these features in patients with NBCCS ranges from 26-80% for hypertelorism and 7-36% for myelinated retinal nerve fiber layer. Prevalence of nystagmus in patients with NBCCS was found to be approximately 6%. Systemic findings such as bilamellar calcification of the falx cerebri, palmar pits, and odontogenic keratocysts (OKCs) are also prevalent., Conclusion: NBCCS may affect numerous organ systems, and thus requires a multidisciplinary team to manage. BCCs and jaw cysts are commonly occurring clinical features that have various surgical excisional options. The ocular anomalies of NBCCS are individually rare, and certain anomalies may present in the amblyogenic period of development and contribute to visual impairment.

Abstract: Basaloid follicular hamartoma (BFH) is a rare, benign follicular neoplasm which typically presents as brown to skin-colored papules on the face, scalp, and trunk. Histologically, BFH consists of cords and strands of basaloid cells forming cystic structures with scant stroma and should be distinguished from infundibulocystic basal cell carcinoma to avoid overly aggressive treatment. Although BFH has been found to be associated with distinct syndromes, including alopecia, myasthenia gravis, and cystic fibrosis, there is often clinical, histopathologic, and genetic overlap with nevoid basal cell carcinoma syndrome (NBCCS). In this article, we describe a case of a 13-year-old patient with NBCCS who presented with multiple BFHs and propose that it its inclusion into the diagnostic criteria for NBCCS be considered., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Nevoid basal cell carcinoma syndrome (NBCCS) is a tumor predisposition condition, the cardinal features of which emerge in adolescence or adulthood. Using statistical optimization, this study proposes NBCCS criteria with improved sensitivity in children less than 18 years of age. Earlier detection may lead to improved surveillance and prevention of sequelae. A survey eliciting medical history was completed by, or on behalf of, individuals with NBCCS. Based on these findings, criteria for suspicion of NBCCS in children were suggested using information from a Bernoulli naïve Bayes classifier relying on the human phenotype ontology. The sensitivity and specificity of the existing and proposed diagnostic criteria were also assessed. Participants (n = 48) reported their first signs of NBCCS appeared at a median age of 8 months, but by our retrospective analysis, they did not fulfill the current diagnostic criteria until a median age of 7 years. This study delineates the early-onset features of NBCCS and proposes criteria that should prompt consideration of NBCCS. Additionally, we demonstrate a method for quantitatively assessing the utility of diagnostic criteria for genetic disorders., (© 2021. The Author(s).)

Gorlin syndrome (MIM 109,400), a cancer predisposition syndrome related to a constitutional pathogenic variation (PV) of a gene in the Sonic Hedgehog pathway (PTCH1 or SUFU), is associated with a broad spectrum of benign and malignant tumors. Basal cell carcinomas (BCC), odontogenic keratocysts and medulloblastomas are the main tumor types encountered, but meningiomas, ovarian or cardiac fibromas and sarcomas have also been described. The clinical features and tumor risks are different depending on the causative gene. Due to the rarity of this condition, there is little data on phenotype-genotype correlations. This report summarizes genotype-based recommendations for screening patients with PTCH1 and SUFU-related Gorlin syndrome, discussed during a workshop of the Host Genome Working Group of the European branch of the International Society of Pediatric Oncology (SIOPE HGWG) held in January 2020. In order to allow early detection of BCC, dermatologic examination should start at age 10 in PTCH1, and at age 20 in SUFU PV carriers. Odontogenic keratocyst screening, based on odontologic examination, should begin at age 2 with annual orthopantogram beginning around age 8 for PTCH1 PV carriers only. For medulloblastomas, repeated brain MRI from birth to 5 years should be proposed for SUFU PV carriers only. Brain MRI for meningiomas and pelvic ultrasound for ovarian fibromas should be offered to both PTCH1 and SUFU PV carriers. Follow-up of patients treated with radiotherapy should be prolonged and thorough because of the risk of secondary malignancies. Prospective evaluation of evidence of the effectiveness of these surveillance recommendations is required., (© 2021. The Author(s).)

Paediatric cardiac tumours are rare, often benign and carry associations with genetic conditions. Cardiac fibromas are mainly composed of fibroblast and connective tissue . They can lead to symptoms due to obstruction of blood flow or arrythmias. In this case, we report an 8-month-old girl child who presented to paediatric cardiology office for cardiac evaluation given a family history of Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, found to have a large 4×4×6 cm fibroma in the apical lateral free wall of the left ventricle and later presented to the emergency department with cardiac arrest., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Basal cell nevus syndrome (BCNS), also known as Gorlin-Goltz syndrome, is a rare autosomal dominant genetic disease. It is thought to be caused by a mutation in the PTCH1 gene, and its incidence is 1/57 000 to 1/256 000. The case of a 7-year-old patient with BCNS and Duchenne muscular dystrophy was reported in this paper.

Background: Nevoid basal cell carcinoma syndrome (NBCCS) is a neurocutaneous disease, characterized by tumorigenesis and developmental anomalies due to aberrant sonic hedgehog (Shh) signaling. Patients with NBCCS typically appear calm and carefree, suggesting that a specific personality in these patients may be associated with an enhanced hedgehog pathway. Our study aimed to determine the personality type in these patients., Methods: We enrolled 14 mentally normal patients with genetically confirmed NBCCS (seven males and seven females; mean age = 25.2 years) and 20 controls (10 males and 10 females; mean age = 27.9 years). The patients were assessed with the Japanese version of the Temperament and Character Inventory, based on the seven-dimensional model of temperament and character, and their clinical symptoms were evaluated. The amygdala volumes of six patients with NBCCS were measured using magnetic resonance imaging with image-processing software., Results: Patients with NBCCS scored significantly lower on harm avoidance (0.89) than controls (1.00; P = 0.0084). Moreover, patients with NBCCS and developmental malformations such as rib anomalies, who may have experienced Shh signaling enhancement from the prenatal period, scored significantly lower on harm avoidance (0.80 [P = 0.0031]). The left amygdala volume was also significantly reduced in patients with NBCCS (P = 0.0426)., Conclusions: Patients with NBCCS who experienced increased Shh signaling from the prenatal period showed significantly lower harm avoidance related to serotonin. The left amygdala volume was significantly reduced in these patients. Our results indicate that Shh signaling may influence the human personality., (© 2020 Japan Pediatric Society.)

Background: Two loci (CHD7 and SOX10) underlying Kallmann syndrome (KS) were discovered through clinical and genetic analysis of CHARGE and Waardenburg syndromes, conditions that include congenital anosmia caused by olfactory bulb (CA/OBs) defects and congenital hypogonadotropic hypogonadism (CHH). We hypothesized that other candidate genes for KS could be discovered by analyzing rare syndromes presenting with these signs. Study Design, Size, Duration: We first investigated a family with Gorlin-Goltz syndrome (GGS) in which affected members exhibited clinical signs suggesting KS. Participants/Materials, Methods: Proband and family members underwent detailed clinical assessment. The proband received detailed neuroendocrine evaluation. Genetic analyses included sequencing the PTCH1 gene at diagnosis, followed by exome analyses of causative or candidate KS/CHH genes, in order to exclude contribution to the phenotypes of additional mutations. Exome analyses in additional 124 patients with KS/CHH probands with no additional GGS signs., Results: The proband exhibited CA, absent OBs on magnetic resonance imaging, and had CHH with unilateral cryptorchidism, consistent with KS. Pulsatile Gonadotropin-releasing hormone (GnRH) therapy normalized serum gonadotropins and increased testosterone levels, supporting GnRH deficiency. Genetic studies revealed 3 affected family members harbor a novel mutation of PTCH1 (c.838G> T; p.Glu280*). This unreported nonsense deleterious mutation results in either a putative truncated Ptch1 protein or in an absence of translated Ptch1 protein related to nonsense mediated messenger RNA decay. This heterozygous mutation cosegregates in the pedigree with GGS and CA with OBs aplasia/hypoplasia and with CHH in the proband suggesting a genetic linkage and an autosomal dominant mode of inheritance. No pathogenic rare variants in other KS/CHH genes cosegregated with these phenotypes. In additional 124 KS/CHH patients, 3 additional heterozygous, rare missense variants were found and predicted in silico to be damaging: p.Ser1203Arg, p.Arg1192Ser, and p.Ile108Met., Conclusion: This family suggests that the 2 main signs of KS can be included in GGS associated with PTCH1 mutations. Our data combined with mice models suggest that PTCH1 could be a novel candidate gene for KS/CHH and reinforce the role of the Hedgehog signaling pathway in pathophysiology of KS and GnRH neuron migration., (© 2020 S. Karger AG, Basel.)

Introduction: Conventional methods of basal cell carcinomas (BCC) treatment bring many severe side effects, especially, if they are repeated many times. The aim of this study is to present the clinical effectiveness of photodynamic method in the treatment and prevention of BCC relapses on the face and to propose a management algorithm., Methods: In a patient with Gorlin-Goltz syndrome (NBCCS) lesions on the face were assessed clinically and with photodynamic diagnostics (PDD), initially and in follow-up every 3 months, for a total of 12 months. Detected BCCs were treated with photodynamic therapy three times every week., Results: In whole follow-up period no clinical relapses were shown. However, in PDD after 6 month in one irradiated and in one initially clinically clear area red fluorescence indicating atypical foci was observed and irradiated additional one time., Discussion: Photodynamic therapy is not limited by previous treatments, can be repeated without adverse events, heals multiple lesions at once and prevents new ones. Because BCC in NBCCS will occur constantly, the implementation of PDD to control the condition of the skin in long-term care should be obligatory. We indicate the validity of using the photodynamic diagnostic and therapy, as a medical procedures of choice., (© 2020 Wiley Periodicals LLC.)

Gorlin syndrome is a skeletal disorder caused by a gain of function mutation in Hedgehog (Hh) signaling. The Hh family comprises of many signaling mediators, which, through complex mechanisms, play several important roles in various stages of development. The Hh information pathway is essential for bone tissue development. It is also the major driver gene in the development of basal cell carcinoma and medulloblastoma. In this review, we first present the recent advances in Gorlin syndrome research, in particular, the signaling mediators of the Hh pathway and their functions at the genetic level. Then, we discuss the phenotypes of mutant mice and Hh signaling-related molecules in humans revealed by studies using induced pluripotent stem cells.