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.
METHODS: 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.

To date, there is no definite effective target therapy or cure for nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome). Basal cell carcinoma is frequently the far most increased risk of this syndrome, including predisposition to other malignancies. In 2015, an 11-year-old female with a past medical history of sickle cell trait, oral, and unilateral knee abscesses presented with multiple visits for various nodules covering the hands and chest, as well as posterior knee cysts. Genetic testing confirmed the diagnosis. The key to treatment and surveillance relies on appropriate recognition, management of atypical presentations, and offering appropriate genetic counseling to families.

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Nevoid basal cell carcinoma syndrome (NBCCS) associated odontogenic keratocysts (OKCs) show more aggressive behavior and it has a higher frequency of relapse than non-syndromic OKCs. Stromal myofibroblasts (MFs), characterized by α-smooth muscle actin (αSMA), desmin and caldesmon expression, and metalloproteinases (MMPs) have an essential role in the remodeling of the extracellular matrix (ECM). The aim of the study is to analyze the immunohistochemical expression of MMP-7, MMP-9, αSMA and other new markers in the study of OKCs MFs such as desmin and caldesmon in NBCCS-associated OKCs compared to recurrent and sporadic keratocysts. Fourty 40 patients (23 M and 17 F) underwent surgery to remove the OKCs. The histological sections in paraffin were incubated with markers antibodies and a semi-quantitative score was used to evaluate the immunoreactivity. Densitometric analysis showed a very significantly increased expression of αSMA, caldesmon, MMP-7 and MMP-9 in NBCCS-OKCs compared to non-syndromic OKCs (p < 0.001). However, desmin showed a not significant increased expression in non-syndromic OKC compared to NBCCS-OKCs specimens in which desmin was slightly or not at all expressed. NBCSS-OKCs showed a greater distribution of MFs compared to the other OKCs subtypes. Further studies will be needed to evaluate whether the different expressions of these markers can be correlated to a different clinical behavior.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

A number of case/family reports have proposed PTCH2 as a putative Gorlin Syndrome (GS) gene, but evidence to support this is lacking. We assessed our cohort of 21 PTCH1/SUFU negative GS families for PTCH2 variants and assessed current evidence from reported cases/families and population data. In our PTCH1/SUFU variant negative GS cohort (25% of total), no pathogenic or likely pathogenic PTCH2 variants were identified. In addition, none of the previously published PTCH2 variants in GS families/cases could be considered pathogenic or likely pathogenic using current guidelines. The absence of clear pathogenic variants in GS families and the high frequency of Loss-of-function (LoF) variants in the general population, including the presence of homozygous LoF variants without a clinical phenotype, mean that it is untenable that PTCH2 is a GS gene. PTCH2 should not be included in panels for genetic diagnosis of GS.

Gorlin-Goltz Syndrome also known as Nevoid Basal Cell Carcinoma Syndrome is an autosomal dominant multisystem disorder. It is characterized by basal cell carcinomas, odontogenic keratocysts, skeletal abnormalities and in a minority of female patients bilateral calcified ovarian fibromas. It is challenging to radiologically assess ovarian fibromas as they have similar imaging patterns to some malignant ovarian lesions. However, it is vitally important to differentiate between benign and malignant lesions to determine patients\' suitability for fertility-sparing surgery. This report describes a case of a 25 year-old patient with Gorlin-Goltz Syndrome and bilateral ovarian fibromas.

Nevoid Basal Cell Carcinoma Syndrome (NBCCS) or Gorlin syndrome is an autosomal dominant disorder characterized by cancer predisposition and multiple developmental defects. Syndrome related disorders have been attributed to alterations of PTCH gene, which plays an important role in Shh signalling pathway. Unresolved complexities of the pathway impede understanding of mechanisms through which PTCH alterations lead to variable phenotype expression in Gorlin syndrome patients, while the role of chromosomal instability is not yet clear. To increase our understanding of NBCCS, every manifestation of the syndrome and associated genetic damage should be seriously considered. Therefore, several atypical NBCCS cases are presented in this paper.

The figurative arts and precisely the ancient Pompeian wall paintings portraits can provide an additional source of information in supplementing bio-anthropological studies. There are several genetic diseases with a wide spectrum of congenital bone stigmata in association to distinctive facial features. Gorlin-Goltz syndrome, also named nevoid basal cell carcinoma syndrome, is an autosomal dominant syndrome characterized by unusual skeletal changes, such as macrocephaly, facial asymmetry, hypertelorism, frontal and parietal bossing caused by germline mutations of the gene PTCH1. The Gorlin syndrome, clinically defined in 1963, existed during Dynastic Egyptian times, as revealed by a spectrum of skeletal findings compatible with the syndrome in mummies dating back to three thousand years ago and, most likely, in the ancient population of Pompeii. In the present research, we discuss the potential relationship between Pompeian wall paintings portrait and the cranio-metric bone changes revealed among the Pompeian skull collections assuming that the ancient portraits can constitute an important tool that should be strictly integrated with osteologic and biomolecular data in order to argue a syndromic diagnosis in ancient population.

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by bone and skin abnormalities and a predisposition to various tumors. Keratocystic odontogenic tumors (KCOTs), which are common tumors of the jaw that cause extensive damage to the jawbone, are usually accompanied with NBCCS. Germline PTCH1 mutations in NBCCS tumorigenesis have been frequently studied; however, little is known regarding the pathogenesis of bone abnormalities in this disease. This study sought to investigate the mechanism underlying heterozygous PTCH1 mutation-mediated abnormal bone metabolism in patients with NBCCS. Stromal cells were isolated from the fibrous capsules of patients with NBCCS-associated or non-syndromic keratocystic odontogenic tumors and non-syndromic tumor stromal cells without PTCH1 mutations served as controls. Germline PTCH1 heterozygous mutations were confirmed in all NBCCS samples and differential protein expression was identified using tandem mass tag-labeled proteomics analysis. Our findings revealed that osteonectin/SPARC expression was significantly downregulated in syndromic stromal cells compared with non-syndromic stromal cells. SPARC expression was even lower in stromal cells carrying PTCH1 protein truncation mutations. PTCH1 siRNA transfection demonstrated that SPARC downregulation correlates with decreased PTCH1 expression. Furthermore, exogenous SPARC promoted osteogenic differentiation of syndromic stromal cells with enhanced development of calcium nodules. In addition, bone mineral density tests showed that patients with NBCCS exhibit weak bone mass compared with sex- and age-matched controls. This study indicates that germline PTCH1 heterozygous mutations play a major role in bone metabolism in patients with NBCCS, in particular in those with PTCH1 protein truncation mutations. SPARC may represent an important downstream modulator of PTCH1 mediation of bone metabolism. Thus, bone mineral density monitoring is critical for patients with NBCCS for prevention of osteoporosis. In addition, surgical procedures on syndromic-associated KCOTs should be performed with consideration of the weaker bone mass in such patients. © 2016 American Society for Bone and Mineral Research.