Early diagnosis of nevoid basal cell carcinoma syndrome.

BACKGROUND: Nevoid basal cell carcinoma syndrome, or NBCCS, is a hereditary condition characterized by basal cell carcinomas, or BCCs; odontogenic keratocysts, or OKCs; and skeletal abnormalities. The authors conducted this study to determine the early signs of NBCCS. METHODS: The authors reviewed files from two Italian dental schools from January 1980 to January 1995 to determine the early signs of NBCCS and the age at which patients were first examined. They re-examined all of the patients, using the diagnostic criteria for NBCCS. RESULTS: The authors found 14 patients who fulfilled the criteria for diagnosis of NBCCS in five families. All of the patients were 16 years of age or younger. In 11 cases (78 percent), the first sign of NBCCS in the patients was an OKC. The OKCs diagnosed in patients older than 13 years of age were large and characterized by widespread bone resorption. One 11-year-old patient had six large OKCs. The authors also found a case of multiple OKCs in an 8-year-old patient. Only one patient showed BCCs. CONCLUSIONS: OKCs are often the first signs of NBCCS and can be detected in patients younger than 10 years of age. Our data suggest that OKCs arise earlier in patients who have NBCCS than in patients who do not have NBCCS. The patients' young ages explain the low incidence of BCCs in this study. CLINICAL IMPLICATIONS: The presence of multiple OKCs in a child or onset of BCC in a patient younger than 20 years of age should alert dentists to the possibility of the patient's having NBCCS.     

Odontogenic keratocyst and uterus bicornis in nevoid basal cell carcinoma syndrome: case report and literature review

Nevoid basal cell carcinoma syndrome (NBCCS), an autosomal dominant disorder with a high degree of penetrance and variable expressivity, is characterized by basal cell carcinomas, odontogenic keratocysts, palmar and/or plantar pits, and ectopic calcifications of the falx cerebri. More than 100 minor criteria have been described, but 2 major and 1 minor criteria or 1 major and 3 minor criteria are necessary for the diagnosis. In this report we present an 8-year-old girl affected by NBCCS showing a uterus bicornis, a hitherto unreported association. However, further research is needed to confirm the association between NBCCS and mullerian fusion defects and to assess the hypothesis that focuses on chromosome 9 the mutant gene for NBCCS and fusion defects of female genital tract.     

Nevoid basal cell carcinoma syndrome: a 17‐year study of 19 cases in Iranian population (1991–2008)

J Oral Pathol Med (2010) 39 : 677–680 Background: Nevoid basal cell carcinoma syndrome (NBCCS) is a hereditary autosomal dominant disorder with a wide range of clinical signs and symptoms. The major criteria are more than two basal cell carcinoma, keratocystic odontogenic tumor, three or more palmar pits, and calcification of the falx cerebri, spine and rib anomalies, and a family history of the syndrome. Methods: This study reports 19 cases in an Iranian population and presents this rare syndrome as a differential diagnosis of skeletal anomalies. Between 1991 and 2008, the demographic, clinical, radiologic and histologic data of 19 patients with NBCCS were analyzed. Results: The average age at the time of diagnosis of NBCCS was 35.12 years. All patients had a minimum of two major criteria. The major criteria with the most frequency were the keratocysts odontogenic tumor (19 patients), and the average number was 6.2. Basal cell carcinoma (8 patients), and the average number was 14.7 calcification of the falx cerebri (17 patients), palmo‐plantar pits (14 patients), mild hypertelorism (10 patients), and bilateral cleft lip and palate (1 patient). Only one patient was affected with an unusual case of NBCCS in a 30‐year‐old man with an associated squamous cell carcinoma of the maxillary sinus. Only two cases of this unusual association have been reported. This case is one of a large family including 14 NBCCS‐affected patients.     

Nevoid basal cell carcinoma syndrome: a review of the literature and a report of a case

The purpose of this paper is to report the development of multiple odontogenic keratocysts (OKCs) in a 15-year-old female with nevoid basal cell carcinoma syndrome (NBCCS) and review the literature pertinent to NBCCS. Although more than 100 abnormalities have been reported in NBCCS, the development of OKCs is one of its principle features. In view of this, the patient was subjected to further medical, dermatological and radiographic investigation. Multiple basal cell naevi and skeletal anomalies associated with NBCCS were found. Because of the autosomal dominant inheritance of this syndrome, the patient's family was then investigated. The patient's father was found to have multiple OKCs. The report highlights the need for vigilance in considering the diagnosis of NBCCS in all cases of OKCs, particularly those affecting young patients.     

Ameloblastoma associated with the nevoid basal cell carcinoma (Gorlin) syndrome

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by a wide range of clinical signs and symptoms. The major criteria for the diagnosis are multiple cutaneous basal cell carcinomas, multiple odontogenic keratocysts of the jaw, palmar and plantar pits, and skeletal abnormalities. Here, we report an unusual case of NBCCS in a 68-year-old woman with late onset of clinical signs and symptoms and with an associated ameloblastoma. Only 4 other cases of this unusual association have been reported.     

A case of central odontogenic fibroma of the mandible in a nevoid basal cell carcinoma syndrome patient

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by tumorigenesis and physical deformities. Although more than 50 clinical manifestations have been described, only two major criteria or one major and two minor criteria are necessary for diagnosis. The most frequently observed manifestation in the oral and the maxillofacial region is an odontogenic keratocyst. In this study, we describe a 14-year-old boy with a diagnosis of NBCCS who presented with a central odontogenic fibroma (COF) in the mandible. This report highlights the importance of precise diagnosis and the choice of surgical method for COF.     

痣样基底细胞癌综合征伴先天性左眼缺失1例

痣样基底细胞癌综合征（NBCCS）又称基底细胞痣综合征或Goltz-Gorlin综合征，是一种复杂且罕见的常染色体显性遗传疾病，大量研究文献证实PTCH1基因与NBCCS有关。本文报道1例NBCCS伴先天性左眼缺失的病例，并结合相关文献探讨以进一步了解该综合征。     

The odontogenic keratocyst and its occurrence in the nevoid basal cell carcinoma syndrome

There are histologic differences between odontogenic keratocysts occurring in the basal cell carcinoma syndrome (NBCCS) and as single lesions in otherwise healthy persons. This study identifies certain differences in age, gender, and site between the two groups. The age at removal of the first keratocyst is significantly lower in the syndrome group. On more thorough examination, patients with multiple keratocysts (excluding recurrences) are found to have other features of NBCCS. The term multiple cysts refers to the lifetime history of the patient and does not necessarily imply that more than one cyst is present at any one time.     

Odontogenic keratocyst clinically mimicking an eruption cyst: report of a case

This article describes a case of odontogenic keratocyst (OKC) in a 1 year and 7 month old girl who presented such a lesion mimicking an eruption cyst. To date, only one well-documented OKC occurring in a patient under 5 years old has been reported and it was thought to be associated with nevoid basal cell carcinoma syndrome (NBCCS). In our OKC case, the cyst was totally enucleated. No evidence of recurrence and NBCCS was found after a 4-year follow-up. The development of involving tooth in a growing child and the histogenesis of OKC are discussed in this article.     

A mandibular swelling

Nevoid basal cell carcinoma syndrome (NBCCS) is characterised by skeletal anomalies, cutaneous basal cell carcinomas and multiple keratocysts. NBCCS is an autosomal dominant disorder, but can have a variable phenotypic penetration. NBCCS can also arise spontaneously. The prevalence is 1:60.000 and 50-65% of patients with NBCCS have affected family members. A recently diagnosed patient is presented and the manifestations of the syndrome are discussed.     

PTCH1 and SMO gene alterations in keratocystic odontogenic tumors

Keratocystic odontogenic tumors (KCOTs, previously known as odontogenic keratocysts) are aggressive jaw lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (NBCCS). Mutations in the PTCH1 (PTCH) gene are responsible for NBCCS and are related in tumors associated with this syndrome. Mutations in the SMO gene have been identified in basal cell carcinoma and in medulloblastoma, both of which are features of NBCCS. To clarify the role of PTCH1 and SMO in KCOTs, we undertook mutational analysis of PTCH1 and SMO in 20 sporadic and 10 NBCCS-associated KCOTs, and for SMO, 20 additional cases of KCOTs with known PTCH1 status were also included. Eleven novel (1 of which occurred twice) and 5 known PTCH1 mutations were identified. However, no pathogenic mutation was detected in SMO. Our findings suggest that mutations are rare in SMO, but frequent in PTCH1 in sporadic and NBCCS-associated KCOTs. Abbreviations: NBCCS, nevoid basal cell carcinoma syndrome; KCOTs, keratocystic odontogenic tumors; BCCs, basal cell carcinomas.     

Familial multiple odontogenic keratocysts

Multiple odontogenic keratocysts (OKCs) are principle features of nevoid basal cell carcinoma syndrome (NBCCS; Gorlin-Goltz syndrome). NBCCS is a genetic disorder transmitted by an autosomal dominant gene with variable expressivity, which is important to recognize when a patient has multiple OKCs. The cysts of the jaws are among the most common findings. Another feature is a certain appearance of the face, such as: large calvaria, high-arched eyebrows, broad nasal root, and mild hypertelorism. Before-therapy diagnosis is, therefore, as important as after-therapy diagnosis. Genetic counseling and examination may also be indicated. The purpose of this paper was to present a family case report of nevoid basal cell carcinoma syndrome with multiple odontogenic keratocysts. The features identified by these combined clinical, imaging, and histologic findings are described, along with a brief mention of the family history and a review of the literature.     

Immunohistochemical analysis of the biological potential of odontogenic keratocysts

BACKGROUND: The aim of this study was to analyse the usefulness of detecting important apoptosis and proliferation markers in assessing the biological potential of odontogenic keratocysts (OKC) and thus selecting the optimal diagnostic algorithm for these lesions. METHODS: Indirect immunohistochemistry and relevant statistical methods were used for analysis of formalin-fixed and paraffin-embedded samples from 98 patients. RESULTS: Nevoid basal cell carcinoma syndrome (NBCCS) keratocysts were characterized by higher expression of Bcl-2, p27Kip1 and c-erbB-2 as well as by lower proliferative activity measured by Ki-67 in basal cell epithelium and by a lower inflammatory response in comparison with sporadic keratocysts. Dentigerous, radicular and non-specified odontogenic cysts differed from both NBCCS and sporadic keratocysts in a wide spectrum of apoptosis and/or cell cycle-related protein expressions, higher proliferation in the basal cell layer, and vice versa, lower proliferation in the suprabasal cell layer. CONCLUSIONS: The NBCCS keratocysts have a different immunophenotype from sporadic keratocysts and both types are distinguishable from dentigerous, radicular and non-specified odontogenic cysts. These findings confirm the separate biological potential of these lesions and the results of the immunohistochemical analysis have diagnostic and prognostic implications.     

Investigation of chromosome 9q22.3-q31 DNA marker loss in odontogenic keratocysts

Multiple basal cell carcinomas and odontogenic keratocysts of the jaws are a feature of the inherited naevoid basal cell carcinoma syndrome (NBCCS), although both occur more commonly as single, sporadic cases. The NBCCS gene has been mapped to chromosome 9q22.3-q31 and loss of heterozygosity for DNA markers from this region has been observed in familial and sporadic basal cell carcinomas. Based on these observations, we undertook a pilot study to determine if a similar pattern of chromosome loss occurs in odontogenic keratocysts. DNA extracted from microdissected odontogenic keratocyst epithelium was examined for loss of heterozygosity for six polymorphic DNA markers mapping to human chromosome 9q22.3-q31. Allelotype loss was detected in epithelium from three, single, sporadic odontogenic keratocysts. These results implicate homozygous inactivation of the NBCCS gene in the initiation and progression of the odontogenic keratocyst.     

痣样基底细胞癌综合征1例报道

痣样基底细胞癌综合征(nevoid basal cell carcinoma syndrome,NBCCS)是一种少见的常染色体显性遗传病,临床表现多达一百多种,主要临床表现为皮肤基底细胞癌,颌骨牙源角化囊性瘤（odontogenic keratocystic tumor, OKC）,手掌及脚底的过度角化、点状凹陷,颅骨异常,小脑镰钙化,眶距增宽,面部畸形,巨头巨脑畸形,唇腭裂等。本文报告1例痣样基底细胞癌综合征,并结合相关文献对该病的发病机制、发病率、临床表现、诊断、治疗方法等进行讨论。     

Contributions of PTCH gene variants to isolated cleft lip and palate.

OBJECTIVE: Mutations in patched (PTCH) cause the nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin syndrome. Nevoid basal cell carcinoma syndrome may present with developmental anomalies, including rib and craniofacial abnormalities, and predisposes to several tumor types, including basal cell carcinoma and medulloblastoma. Cleft palate is found in 4% of individuals with nevoid basal cell carcinoma syndrome. Because there might be specific sequence alterations in PTCH that limit expression to orofacial clefting, a genetic study of PTCH was undertaken in cases with cleft lip and/or palate (CL/P) known not to have nevoid basal cell carcinoma syndrome. RESULTS: Seven new normal variants spread along the entire gene and three missense mutations were found among cases with cleft lip and/or palate. One of these variants (P295S) was not found in any of 1188 control samples. A second variant was found in a case and also in 1 of 1119 controls. The third missense (S827G) was found in 5 of 1369 cases and in 5 of 1104 controls and is likely a rare normal variant. Linkage and linkage desequilibrium also was assessed using normal variants in and adjacent to the PTCH gene in 220 families (1776 individuals), each with two or more individuals with isolated clefting. Although no statistically significant evidence of linkage (multipoint HLOD peak = 2.36) was uncovered, there was borderline evidence of significant transmission distortion for one haplotype of two single nucleotide polymorphisms located within the PTCH gene (p = .08). CONCLUSION: Missense mutations in PTCH may be rare causes of isolated cleft lip and/or palate. An as yet unidentified variant near PTCH may act as a modifier of cleft lip and/or palate.     

Elongated styloid process associated with nevoid basal cell carcinoma syndrome

This article presents a case with nevoid basal cell carcinoma syndrome (NBCCS) and an elongated styloid process. Basal cell carcinoma syndrome, also known as Gorlin-Goltz syndrome, is an autosomal dominant inherited syndrome manifested by multiple defects involving the skin, nervous system, eyes, endocrine system, and bones. Elongated styloid process or calcified stylohyoid ligament cause craniofacial or cervical pain. The actual cause of elongation of the styloid process or the calcification of the stylohyoid ligament is unclear. The cause of elongation of styloid process in this case may be the calcification induced by NBCCS. This report is the first case presentation of NBCCS with elongated styloid process. Elongated styloid process might be described as an anomaly of an NBCCS.     

Imaging modality correlations of an odontogenic keratocyst in the nevoid basal cell carcinoma syndrome: a family case report

Multiple maxillary and mandibular cysts are principle features of nevoid basal cell carcinoma syndrome (NBCCS; Gorlin-Goltz syndrome). We present a family case report of NBCCS with odontogenic keratocyst where the findings on plain films, CT, clinical, and histopathologic examinations are compared and analyzed. The systemic manifestations included frontal bossing, odontogenic keratocyst, ectopic calcification in 1 patient, and bifid rib in 1 patient. CT examination displayed aspects of bone morphology not visible on the plain films. Odontogenic keratocyst diagnosis was confirmed by histopathological examination. The features identified by these combined clinical, imaging, and histologic findings are helpful in identifying an NBCCS patient, distinguishing keratocyst from others cysts or neoplasic lesions, and can therefore influence surgical management. NBCCS is a rare autosomal dominant cancer predisposition syndrome, which is important to recognize when a patient has multiple odontogenic keratocysts, because lifelong monitoring is essential for patient management.     

New mutation of the patched homologue 1 gene in a Chinese family with naevoid basal cell carcinoma syndrome

Naevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is inherited in an autosomal dominant mode characterised by a combination of developmental anomalies and a predisposition to form tumours. Our aim was to search for patched homologue 1 (PTHC1) mutations in a Chinese family with NBCCS. Mutation analysis of PTCH1 was done of all 10 members of this family by amplified polymerase chain reaction and direct sequencing. Two novel PTCH1 mutations (3146A→T, 1686C→T) were identified in all five affected members. The mutation, 3146A→T in exon 17, is predicted to lead to different PTCH protein translations. 1686C→T mutation in exon 11 is a nonsense mutation. These mutations were not found in any unaffected members of this family or in 100 unrelated healthy Chinese people. Our findings suggest that the 3146A→T mutation in the PTCH gene may be the cause of NBCCS by affecting the conformation and function of the PTCH protein.