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 case report and overview on diagnosis and management

Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is a rare condition characterized by varied clinical manifestations like multiple Basal Cell Carcinomas (BCC), multiple Keratocystic Odontogenic Tumours (KCOT), palmar and/or plantar pits and ectopic calcification of the falx cerebri, which are considered as the major criteria for diagnosis. The occurrence of jaw manifestations makes it an important diagnostic problem for oral and maxillofacial surgeons and often clinicians encounter this aspect which finally leads to the diagnosis of this syndrome. This paper reports a case of NBCCS and provides an overview on the diagnosis and management of this enigmatic entity.     

Situs inversus in a patient with nevoid basal cell carcinoma syndrome: a histogenetic relationship?

Nevoid basal cell carcinoma syndrome (NBCCS) is an uncommon autosomal dominant inherited disorder with high penetrance and variable expressivity. It affects multiple organ systems, including the stomatological, skeletal, skin, eye, reproductive, and central nervous systems. It is caused by mutations in the patched tumor suppressor gene, PTCHI, located in the 9q22.3-q31 chromosome. To our knowledge, this is the first report of a patient with unusual radiological features, i. e. dextrocardia and situs inversus totalis, in conjunction with common features including multiple keratocystic odontogenic tumors, bifid ribs, palmar and plantar pits, bridging of the sella turcica and calcification of the falx cerebri. We examined whether these genetic conditions were associated, as both involve ciliary dysfunction.     

Nevoid basal cell carcinoma syndrome: a retrospective analysis of 33 affected Korean individuals

This article describes a pooled analysis of Korean individuals with nevoid basal cell carcinoma syndrome (NBCCS). The data upon which this review is based has been retrieved from published case reports in Korean dental and medical literature between the years 1981 to 2002. We found 33 subjects who met the diagnostic criteria for NBCCS. Relative frequencies of associated complications are presented and compared with those of the English literature. Odontogenic keratocyst (OKC) and palmar and/or plantar pits, and hypertelorism were the most frequently observed anomalies. OKCs are often the first signs of NBCCS and can be detected in patients younger than 20 years of age. However, the incidence and clinical manifestations of NBCCS in Korean individuals were found to be rather different from those of other countries. The relatively low frequency of basal cell carcinomas and falx calcification among the major criteria were two major differences. The frequencies of the minor criteria concur in general with the ranges given by some others. It is concluded that these differences may be attributed to genetic and geographic differences.     

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。     

Coverage of the cranium with latissimus dorsi in the recurrent basal cell carcinoma of Gorlin syndrome: for protection against clinical invasion

Gorlin's syndrome is a genetic disorder of autosomal dominant inheritance with characterized primarily by five major findings: multiple basal cell carsinoma (BCC), jaw cysts, pits on the palms and soles, ectopic calcification of the falx cerebri and skeletal anomalies. BCC is the most frequently accompanied tumor with this syndrome. The risk of recurrent BCC with Gorlin's syndrome is higher than non-syndromic BCC. The authors present a 25-year-old man affected by recurrent basal cell carcinoma on the scalp. The patient was treated by excising the tumor and reconstructing latissimus dorsi musculocutaneous flap. The fascial component of the scalp forms an additional layer between the skin and the cranium. This structure creates an extra distance before the invasion into the cranium which needs to be penetrated by the skin tumor. Muscle tissue transformed in scalp reconstruction imitates the fascia layer in forming an additional layer against the invasion of skin tumors such as recurrent BCC into the cranium. Free flap reconstruction for recurrent scalp BCC can be best therapy model at Gorlin's syndrome.     

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.     

The basal cell nevus syndrome associated with cleft lip and cleft palate: report of case.

A case of basal cell nevus syndrome with multiple keratocysts, cleft lip and cleft palate, calcification of the falx cerebri, and late appearance of basal cell carcinoma is described.     

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。     

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.     

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.     

Gorlin-Goltz syndrome

Gorlin-Goltz syndrome is an uncommon autosomal dominant inherited disorder, which is characterized by multiple odontogenic Keratocysts and basal cell carcinomas, skeletal, dental, ophthalmic, and neurological abnormalities, intracranial ectopic calcifications of the falx cerebri, and facial dysmorphism. Pathogenesis of the syndrome is attributed to abnormalities in the long arm of chromosome 9 (q22.3-q31) and loss or mutations of human patched gene (PTCH1 gene). Diagnosis is based upon established major and minor clinical and radiological criteria and ideally confirmed by deoxyribo nucleic acid analysis. We report a case of a 9-year-old girl presenting with three major and one minor feature of Gorlin-Goltz syndrome. Radiologic findings of the syndrome are easily identifiable on Orthopantomogram, chest X-ray, and Computed tomography scans. These investigations prompt an early verification of the disease, which is very important to prevent recurrence and better survival rates from the coexistent diseases.     

PCR-SSCP和DNA测序检测牙源性角化囊肿中PTCH基因的突变

目的 检测牙源性角化囊肿（OKC）中PTCH基因突变的特点。方法 采用PCR-SSCP筛查与DNA直接测序的方法对12例OKC进行PTCH基因突变的检测, 其中2例为痣样基底细胞癌综合征（NBCCS）相关OKC,10例为散发OKC。 结果 在4例OKC中发现了4处突变,其中2处生殖细胞突变发生在2例NBCCS相关OKC,2处体细胞突变发生在2例散发OKC。另外,还在10例OKC中检测到了8处PTCH基因多态性。结论 NBCCS相关OKC和散发OKC均可发生PTCH基因突变,但突变水平不同,PTCH基因的突变在二者的发病中可能均起重要作用。     

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.     

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.     

Multiple basal cell carcinomas and keratocysts - the Gorlin and Goltz syndrome.

This paper is based on our experience with the Gorlin-Goltz syndrome and on data from 14 patients of the Nordwestdeutsche Kieferklinik in whom this disorder was detected, treated and followed up. A clinical concept has been produced, with a diagnostic check list including a genetic and a dermatological routine work up as well as a radiological survey of the jaws and skeleton. Whenever multiple basal cell carcinomas plus the typical jaw lesions are found in a patient, the diagnosis is easy. A minimum diagnostic criterion is the combination of either the skin tumours or multiple odontogenic keratocysts plus a positive family history for this disorder, bifid ribs, lamellar calcification of the falx cerebri or any one of the skeletal abnormalities typical of this syndrome. All those in whom this disorder is diagnosed or suspected should be followed up for the rest of their lives. The family should be examined and genetic counselling should be offered.     

Basal cell nevus syndrome: clinical and genetic diagnosis

Introduction

Basal cell nevus syndrome (BCNS), also known as Gorlin–Goltz syndrome, comprises five main pathological features: nevoid basal cell carcinomas, keratocystic odontogenic tumors, congenital skeletal anomalies, calcification of the falx cerebri, and point skin depressions on the palms and/or soles. The disease exhibits a dominant autosomal hereditary trait, with implication of the human homologue of the Drosophila segment polarity Patched (PTCH) gene. BCNS is diagnosed on the basis of clinical and radiological criteria and can be confirmed by genetic study. The patient prognosis is very good, with normal life expectancy in most cases.

Methods

The present study reports two cases of BCNS with the presence of maxillo-mandibular keratocystic odontogenic tumors.

Results

One case was diagnosed according to clinical criteria, while the other required genetic confirmation that revealed a germ line mutation in exon 17 (c.2868delC), not previously described in the databases, which was considered to be responsible for the disease.