Gorlin-Goltz Syndrome: A Case Series Highlighting Oral and Maxillofacial PresentationsAbstractObjective: Gorlin–Goltz syndrome (GGS) is a rare autosomal dominant disorder characterized by multisystem involvement and marked phenotypic variability, often leading to delayed diagnosis. This report aims to present the variable oral and maxillofacial manifestations of GGS. Materials and Methods: This observational case series documents three patients (13-year-old female, 17-year-old male, 56-year-old female) presenting with multifocal jaw lesions. Diagnosis was established via clinical evaluation, panoramic radiography, computed tomography (CT), and histopathological analysis. Systemic investigation was prompted by oral findings. Results: All patients met the diagnostic criteria for GGS primarily through maxillofacial lesions. The consistent hallmark was the presence of multiple odontogenic keratocysts (OKs). Unique findings included an odontogenic myxoma and an ovarian fibroma in the youngest patient, and falx cerebri calcification in the two older patients. A familial history was present in one case. None presented with basal cell carcinomas (BCCs) at the time of diagnosis or treatment, demonstrating a phenotype dominated by oral and skeletal features. Conclusion: This series demonstrates that GGS can manifest with prominent maxillofacial findings in the absence of cutaneous signs. The occurrence of multiple OKs, especially in young patients, is a potent indicator of the syndrome. Dentists are pivotal in the initial recognition of GGS, enabling timely diagnosis and the institution of multidisciplinary management to improve patient outcomes.Keywords: Gorlin-Goltz Syndrome, Nevoid Basal Cell Carcinoma Syndrome, Odontogenic Keratocyst, Odontogenic MyxomaKey Clinical MessageEarly recognition of multiple odontogenic keratocysts and characteristic craniofacial or radiographic findings is essential for diagnosing Gorlin–Goltz syndrome. Dental and maxillofacial specialists play a pivotal role in initiating timely investigation, guiding multidisciplinary management, and preventing delayed identification of this multisystem disorder.IntroductionNevoid basal cell carcinoma syndrome (NBCCS), also known as basal cell nevus syndrome or Gorlin–Goltz syndrome (GGS), is a rare autosomal dominant disorder characterized by a broad spectrum of developmental abnormalities and a marked predisposition to neoplasms1,2. The syndrome demonstrates high penetrance with variable expressivity, meaning that most affected individuals develop clinical manifestations, though the severity and presentation may vary widely even within the same family1,3,4.The pathophysiology of GGS is intrinsically linked to mutations in the PTCH gene (the human homolog of the patched gene in Drosophila), particularly PTCH1, located on chromosome 9q22.3–q311,3-5. Mutations in PTCH2 (1p32) and SUFU (10q24.32) have also been reported1,4,5. These genes function as tumor suppressors within the Hedgehog signaling pathway, and their dysregulation promotes uncontrolled cell proliferation and tumorigenesis4,5.Clinically, GGS presents with multisystem involvement, with more than 40 associated manifestations described1,3. Common features include multiple basal cell carcinomas (BCCs) and other dermatological alterations, odontogenic keratocysts (OKs), and skeletal abnormalities affecting the ribs, vertebral column, and skull, sometimes associated with cleft lip and/or palate. Ectopic calcifications of the central nervous system are frequent, particularly lamellar calcification of the falx cerebri, as well as calcification of the tentorium cerebelli, petroclinoid ligament, diaphragma sellae, and partial or complete bony bridging of the sella turcica. Additional findings may include ocular, genitourinary, and cardiovascular anomalies, as well as low-frequency neoplasms such as medulloblastomas, meningiomas, and ovarian or cardiac fibromas1,6,7.Within the field of dentistry, several oral and maxillofacial abnormalities have been identified as manifestations of Gorlin–Goltz syndrome (GGS), including odontogenic keratocysts (OKs), dental agenesis, malocclusion and dentofacial deformities, neoplasms such as maxillary fibrosarcoma, ameloblastoma, odontogenic myxoma, spindle cell carcinoma, and squamous cell carcinoma, as well as other craniofacial abnormalities1,6. The occurrence of multiple OKs is a key diagnostic indicator and is recognized as one of the major criteria for GGS1,6. In fact, jaw cysts are often the most common clinical feature of the syndrome2,8. A clinical diagnosis of GGS is established when two major criteria, or one major and two minor criteria, are present1.Through a series of three cases, this report aims to present the variable oral and maxillofacial manifestations of Gorlin–Goltz syndrome (GGS), emphasizing the diagnostic features of theses lesions. The clinical and radiographic findings are detailed to highlight the pivotal role of dental and maxillofacial specialists in the early recognition and diagnosis of this multisystem disorder.Material and MethodsThis observational case series study was designed to document the oral and maxillofacial manifestations associated with GGS base on three cases.Ethical Considerations and Confidentiality: The study received ethical clearance from the local Ethical Committee for Human Research, under approval number 8.049.321 (CAAE: 93991025.1.0000.0105), ensuring adherence to ethical research standards. Each image was de-identified by removing any discernible patient information, including facial features or unique identifiers that could potentially reveal the patient’s identity.Patient 1A 13-year-old female patient initially presented with a history of previous mandibular and maxilla lesions. The previous panoramic radiograph revealed a complex picture with three major radiolucent lesions: a unilocular lesion at right body of the mandible, a pericoronal radiolucency surrounding the unerupted tooth 37, and a third lesion in the maxilla associated with the impacted teeth 14 and 15 (Figure 1-A). The patient had performed previous surgical treatments under general anesthesia and biopsies were performed. The lesion in right mandible was diagnosed as odontogenic myxoma. Lesions in left mandible (around tooth 37) and in right maxilla were enucleated as cyst-like lesions and the histopathological revealed that both as odontogenic keratocysts (OKs). The actual presentation revealed recurrence of the odontogenic myxoma in left mandible (Figure 1-B) and an additional cyst like lesion in left mandible between the teeth 32-33 (Figure 1-C), also diagnosed as OK.The presence of multiple OKs, a major criterion for Gorlin-Goltz Syndrome, prompted further systemic investigation. The patient’s report of occasional abdominal pain and non-menstrual vaginal bleeding led to an MRI, which identified a calcified ovarian fibroma, another major criterion for the syndrome. This confirmed the diagnosis of GGS. Screening of the parents revealed no signs of the syndrome, suggesting ade novo mutation in the patient case or very lower penetrance of the disease in one of the parents. No additional case in the family was reported. Additional information for patient 1 is described in table 1.Patient 2A 17-year-old male patient sought dental evaluation due to multiple bone lesions in the maxillofacial region previously identified at another healthcare facility. At the time of presentation, there was no prior diagnosis of Gorlin–Goltz syndrome (GGS). His medical history included a craniotomy (craniosynostosis) performed at five months of age and previous oral surgeries conducted at another institution. A retrieved panoramic radiograph taken when the patient was 13 years old revealed three radiolucent areas, two in the mandible and one in the maxilla (Figure 2A). The patient had not received appropriate diagnostic investigation or follow-up at that time.Computed tomography demonstrated multiple cystic-like lesions in both the maxilla and the mandible bilaterally (Figure 2B-C). These lesions showed anteroposterior growth, mild cortical expansion in the posterior mandible, and extension into the maxillary sinuses. All four lesions were later confirmed histopathologically as odontogenic keratocysts (OKs). Additionally, calcification of the falx cerebri was observed, further supporting the diagnosis of Gorlin–Goltz syndrome (Figure 2D). Clinical examination revealed a Class III skeletal profile, anterior crossbite, and a high-arched palate (dentofacial deformity) (Figure 2E). No other family members were reported to have GGS or a history of maxillofacial bone lesions. Additional information for patient 2 is described in table 1.Patient 3A 56-year-old female patient with a medical history of type 2 diabetes mellitus, systemic arterial hypertension, hypothyroidism, and coronary artery disease (status post–cardiac catheterization ten years earlier) sought dental care due to pain and swelling in the right maxillary region. She had a previously established diagnosis of Gorlin–Goltz syndrome (GGS) and reported a history of odontogenic keratocyst (OK) diagnosed at another healthcare facility. The patient also reported having a son affected by the same condition.Computed tomography (CT) (Figure 3A-D) demonstrated multilocular bone lesions in the posterior mandible bilaterally, as well as a cystic lesion in the right maxillary alveolar process extending into the ipsilateral maxillary sinus. Calcification of the falx cerebri was also noted. Histopathological analysis of biopsies from both mandibular and maxillary lesions confirmed the diagnosis of odontogenic keratocysts. Additional information for patient 3 is described in table 1.DiscussionGorlin–Goltz syndrome (GGS) is a rare autosomal dominant multisystem disorder characterized by high penetrance and variable expressivity, leading to significant phenotypic heterogeneity1,4,5,9,10. This variability often contributes to delayed or missed diagnosis, particularly when the initial manifestations occur in the oral and maxillofacial region rather than in the skin or skeletal system2,9,10. Among the multiple features described, odontogenic keratocysts (OKs) are the most consistent and representative oral manifestation of GGS, occurring in 65% to 100% of affected individuals1,4,9. These lesions frequently appear as the first clinical sign of the syndrome, usually during the first or second decades of life, and their recurrent or multifocal presentation serves as a crucial diagnostic indicator6,8,11,12.The maxillofacial region, therefore, plays a pivotal role in the early recognition of GGS. Radiographically, OKs appear as lytic, expansile cystic lesions that commonly involve the mandibular body, rami, and occasionally the maxilla5,9. In the present series, panoramic radiography and computed tomography revealed characteristic multilocular radiolucencies, mild cortical expansion, and sinus involvement consistent with multiple OKs. Intracranial calcifications, particularly of the falx cerebri observed in Patients 2 and 3, provided additional evidence supporting the diagnosis. Distinctive craniofacial features, such as frontal bossing, hypertelorism, macrocephaly, malocclusion, impacted teeth, and dental agenesis, were also noted but specially in the case 2, finding well aligned with the classic clinical spectrum of GGS1. Collectively, these observations emphasize that dental and maxillofacial professionals are often the first to identify the radiographic and clinical hallmarks of Gorlin–Goltz syndrome, enabling timely diagnosis, genetic counseling, and multidisciplinary management before dermatological or systemic complications arise1,3,5.In Gorlin–Goltz syndrome, basal cell carcinomas (BCCs) represent a hallmark cutaneous manifestation and may affect up to 90% of white patients1,5. However, BCCs may be absent in some individuals, as observed in the present series, where all three patients exhibited primarily maxillofacial lesions without cutaneous or major systemic involvement. This variation is attributed to the disorder’s genetic characteristics, particularly its autosomal dominant inheritance with high penetrance but variable expressivity1,4,10. Furthermore, de novo mutations, reported in up to 35–60% of cases, may account for sporadic presentations and the absence of family history1,4. These findings emphasize that the absence of BCCs does not exclude the diagnosis of GGS, reinforcing the importance of recognizing its oral and maxillofacial hallmarks for early identification and management.The present case series underscores the heterogeneous expression of Gorlin–Goltz syndrome and highlights that maxillofacial manifestations can represent the predominant or even sole clinical evidence of the disease. The absence of basal cell carcinomas or other systemic alterations in all three patients reinforces the concept that GGS may initially or exclusively present through odontogenic keratocysts and craniofacial abnormalities. These cases exemplify the diagnostic value of detailed radiographic assessment and emphasize the pivotal role of dentists in identifying pathognomonic features. Early recognition at the dental setting enables appropriate genetic counseling, systematic screening for associated anomalies, and preventive interventions that may reduce morbidity and improve long-term prognosis.ConclusionIn this case series, Gorlin-Goltz syndrome presented with predominantly oral and maxillofacial findings, with multiple and recurrent odontogenic keratocysts serving as the key diagnostic indicators. As dental and maxillofacial professionals are often the first to encounter these signs, they play a critical role in the early detection and multidisciplinary management of this complex genetic disorder.AcknowledgmentsWe wish to thank the Coordination for the Improvement of Higher Education Personnel (CAPES, Ministry of Education, Brazil) for the scholarship granted to Gabriella Schmitz Oliveira, Finance Code 001.FundingThis manuscript did not receive any financial support from any funding agencies, commercial entities, or non-profit organizations.Competing interestsThe authors declare no conflicts of interest.Ethical approvalThe study protocol was approved by the local Institutional Ethics Committee (https://www2.uepg.br/propesp-cep/) under number 8.049.321 (CAAE: 93991025.1.0000.0105). All procedures were conducted in accordance with the ethical standards of the Declaration of Helsinki and all enrolled patients or legal responsible provided a signed informed consent.References1. 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