Focal dermal hypoplasia (goltz-gorlin syndrome): A new case with a novel variant in the PORCN gene (c.1250T>C:p.F417S) and unusual spinal anomaly.

Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome; OMIM 305600) is a disorder that features involvement of the skin, skeletal system, and eyes. It is caused by loss-of-function mutations in the PORCN gene. We report a young girl with FDH, microphthalmos associated with colobomatous orbital cyst, dural ectasia and cystic malformation of the spinal cord, and a de novo variant in PORCN. This association has not been previously reported, and based on these observations the phenotypic spectrum of FDH might be broader than previously appreciated. It would be prudent to alter the suggested surveillance for this rare disorder. © 2013 Wiley Periodicals, Inc.

Ectodermal dysplasia, ectrodactyly, clefting, anophthalmia microphthalmia, and genitourinary anomalies: nosology of goltz-gorlin syndrome versus eec syndrome

We report on two unrelated Brazilian girls born to normal and nonconsanguineous parents and presenting ectodermal dysplasia, ectrodactyly, clefting, tear duct anomalies, and micro/anophthalmia. The clinical picture presented by these patients suggests the diagnosis of Goltz-Gorlin (Focal dermal hypoplasia) syndrome and EEC syndrome.

Gorlin syndrome: Importance of clinical signs and danger of delayed diagnosis A case report with eight years follow-up

Nevoid basal cell carcinoma (NBCCS) or Gorlin-Goltz syndrome (GS) is a multidisciplinary problem, the early diagnosis of which allows secondary prophylaxis that follows an appropriate regimen to delay progression of the syndrome. The aim of this study was to present a case of delayed diagnosis of GS in a young patient who received multidisciplinary treatment 5 years after onset. The patient presented for evaluation with painless swelling of the left maxilla. Histological examination confirmed the diagnosis of a keratocyst odontogenic tumor (KOT) that was enucleated. On presentation, the patient’s symptoms and clinical signs were not related to complications of GS, and the possibility of GS was initially rejected, as he did not have a family history of the syndrome. Four years after the first surgery to remove the lesion, the patient came to our clinic with a brown, pigmented lesion. Computed tomography revealed ectopic lamellar calcification of the falx cerebri, which was the conclusive factor for the diagnosis of GS. It is important that clinicians recognize the clinical signs of GS, which mainly manifests itself as multiple basal cell carcinomas in the skin.

Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC-C loci.

Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant condition mainly characterized by the development of mandibular keratocysts which often have their onset during the second decade of life and/or multiple basal cell carcinoma (BCC) normally arising during the third decade. Cardiac and ovarian fibromas can be found. Patients with NBCCS develop the childhood brain malignancy medulloblastoma (now often called primitive neuro-ectodermal tumor [PNET]) in 5% of cases. The risk of other malignant neoplasms is not clearly increased, although lymphoma and meningioma can occur in this condition. Wilms tumor has been mentioned in the literature four times. We describe a patient with a 10.9 Mb 9q22.3 deletion spanning 9q22.2 through 9q31.1 that includes the entire codifying sequence of the gene PTCH1, with Wilms tumor, multiple neoplasms (lung, liver, mesenteric, gastric and renal leiomyomas, lung typical carcinoid tumor, adenomatoid tumor of the pleura) and a severe clinical presentation. We propose including leiomyomas among minor criteria of the NBCCS.

Gorlin-Goltz Syndrome and Neoplasms: A Case Study

Gorlin syndrome is a rare autosomal dominant disorder exhibiting high penetrance and variable expressivity. It is characterized by facial dysmorphism, skeletal anomalies, multiple basal cell carcinomas, odontogenic keratocysts (OKC), palmar and plantar pits, bifid ribs, vertebral anomalies and a variety of other malformations. Various neoplasms', such as medulloblastomas, meningiomas, ovarian and cardiac fibromas are also found in this syndrome. Objective: To describe a twelve-year-old patient with Gorlin-Goltz syndrome, with basal cell carcinomas and promyelocytic leukemia developed after receiving craniospinal radiation for a medulloblastoma. Mild ribs as well as mandibular and maxillar OKC were also diagnosed. Conclusion: The patient with Gorlin-Goltz syndrome should receive close follow-up for early detection of malformations and malignant neoplasias.

Estudo da imunoexpressão de RANKL e OPG, do índice angiogênico (CD34) e da presença de miofibroblastos (α-SMA) em ceratocistos odontogênicos isolados e associados à síndrome de Gorlin

The odontogenic keratocysts are distinguished from other odontogenic cystic lesions by their potentially aggressive clinical behavior and association, in some cases, with Gorlin syndrome. Studies have suggested that syndrome keratocysts, in comparison with sporadic lesions, have higher growth and infiltration capacity and higher recurrence tendency. The aim of this study was to analyze, by means of immunohistochemistry, the expressions of receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG), the angiogenic index (CD34) and the presence of myofibroblasts (α-SMA) in primary and recurrent sporadic keratocysts and in keratocysts associated with Gorlin syndrome. The sample was composed by 30 sporadic keratocysts (22 primary and 8 recurrent) and 22 syndrome keratocysts. In the epithelium and in the fibrous capsule of the lesions, the immunoexpression of RANKL and OPG was evaluated by determination of the percentage of positive cells, according to the following scores: 0 (less than 10% of positive cells), 1 (11% - 50% of positive cells), 2 (51% - 75% of positive cells) and 3 (more than 76% of positive cells). In addition, cases were classified according to the RANKL score/ OPG score ratio, as follows: RANKL > OPG, RANKL < OPG, and RANKL = OPG. The angiogenic index was analyzed by counting the microvessels immunoreactive to anti-CD34 antibody in 5 fields (200). The analysis of myofibroblasts was performed by counting the cells immunoreactive to anti-α-SMA antibody in 10 fields (400). The analysis of the expressions of RANKL and OPG in the epithelial lining and in the fibrous capsule did not reveal significant differences between groups (p > 0.05). Regarding the RANKL/ OPG ratio in the epithelial lining, most sporadic primary (54.5%) and syndrome lesions (59.1%) showed RANKL < OPG ratio and RANKL = OPG ratio, respectively (p > 0.05). With respect to the RANKL/ OPG ratio in the fibrous capsule, the majority of sporadic primary (81.8%) and sporadic recurrent lesions (75.0%) and most syndrome lesions (45.5%) showed RANKL = OPG ratio (p > 0.05). The mean number of microvessels was 69.2 in sporadic primary lesions, 67.6 in recurrent lesions, and 71.6 in syndrome lesions, with no significant differences between groups (p > 0.05). The mean number of myofibroblasts was 34.4 in sporadic primary lesions, 29.3 in recurrent lesions, and 33.7 in syndrome lesions, with no significant differences between groups (p > 0.05). In conclusion, the results of the present study suggest that the differences in the biological behavior between sporadic keratocysts and keratocysts associated with Gorlin syndrome may not be related to the expressions of RANKL and OPG, the RANKL/ OPG ratio, the angiogenic index or the number of myofibroblasts in these lesions

PTCH1 gene mutations in exon 17 and loss of heterozygosity on D9S180 microsatellite in sporadic and inherited human basal cell carcinomas

Background Basal cell carcinomas (BCCs) are the most frequent human cancer that results from malignant transformation of basal cells in the epidermis. Gorlin syndrome is a rare inherited autosomal dominant disease that predisposes with multiple BCCs and other birth defects. Both sporadic and inherited BCCs are associated with mutations in the tumor suppressor gene PTCH1, but there is still uncertainty on the role of its homolog PTCH2. Objectives To search for mutations and genomic instability in sporadic and inherited BCCs. Methods DNA obtained from leukocytes and tumor cells was amplified by polymerase chain reaction regarding five exons of PTCH1 and PTCH2 and neighboring microsatellites. Exons were sequenced and compared with the GenBank database. Results Only D9S180, of six microsatellites, showed loss of heterozygosity in three BCCs (two sporadic and one inherited). One sporadic BCC presented the mutation g. 2885G>C in exon 17 of PTCH1, which predicts the substitution p.R962T in an external domain of the protein. In addition, the leukocytes and tumor cells of one patient with Gorlin syndrome showed the mutation g. 2839T>G in the same exon and gene, which predicts a p.E947stop and truncated protein. All control and tumor samples presented IVS9 + 217T in intron 9 of PTCH1. Conclusion Mutations found in the PTCH1 gene and neighboring repetitive sequences may have contributed to the development of the studied BCCs.

The role of hedgehog signalling in tumorigenesis

It has long been known from work in both Drosophila and vertebrate systems that the hedgehog signalling pathway is pivotal to embryonic development, but the past 5 years has seen an increase in our understanding of how members of this pathway are crucial to the processes of tumorigenesis. This important link was firmly established with the discovery that mutations in the gene encoding the hedgehog receptor molecule patched are responsible for both familial and sporadic forms of basal cell carcinoma (BCC), as well as a number of other tumour types. It is now known that a number of key members of the hedgehog cascade are involved in tumorigenesis, and dysregulation of this pathway appears to be a key element in the aetiology of a range of tumours. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Visualization of oligonucleotide probes and point mutations in interphase nuclei and DNA fibers using rolling circle DNA amplification

Rolling circle amplification (RCA) is a surface-anchored DNA replication reaction that can be exploited to visualize single molecular recognition events. Here we report the use of RCA to visualize target DNA sequences as small as 50 nts in peripheral blood lymphocytes or in stretched DNA fibers. Three unique target sequences within the cystic fibrosis transmembrane conductance regulator gene could be detected simultaneously in interphase nuclei, and could be ordered in a linear map in stretched DNA. Allele-discriminating oligonucleotide probes in conjunction with RCA also were used to discriminate wild-type and mutant alleles in the cystic fibrosis transmembrane conductance regulator, p53, BRCA-1, and Gorlin syndrome genes in the nuclei of cultured cells or in DNA fibers. These observations demonstrate that signal amplification by RCA can be coupled to nucleic acid hybridization and multicolor fluorescence imaging to detect single nucleotide changes in DNA within a cytological context or in single DNA molecules. This provides a means for direct physical haplotyping and the analysis of somatic mutations on a cell-by-cell basis.

Early diagnosis of Gorlin-Goltz syndrome: case report

The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by keratocystic odontogenic tumors (KCOT) in the jaw, multiple basal cell nevi carcinomas and skeletal abnormities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the KCOTs are usually one of the first manifestations of the syndrome. This article paper reports the case of a patient, a 10-year-old boy with NBCCS, emphasizing its clinical and radiographic manifestations. This study highlights the importance of health professionals in the early diagnosis of NBCCS and in a preventive multidisciplinary approach to provide a better prognosis for the patient.

Blepharo-cheilo-dontic (BCD) syndrome: Report on four new patients

We report on four Brazilian patients with, among other signs, cleft lip and palate, dental anomalies, ectropion of the lower eyelids, euryblepharon, and lagophthalmia, Two were sporadic cases and two were familial cases, a mother and her equally affected son, Recently, the reports with different combination of these signs were reviewed by Gorlin et al, [1996; Am J Med Genet 65:109-112] and named blepharo-cheilo-dontic (BCD) syndrome, Variable expressivity and autosomal dominant inheritance were observed. (C) 1998 Wiley-Liss, Inc.

Multiple Desmoid Tumors In A Patient With Gardner's Syndrome - Report Of A Case.

Desmoid tumor (DT) is a common manifestation of Gardner's Syndrome (GS), although it is a rare condition in the general population. DT in patients with GS is usually located in the abdominal wall and/or intra-abdominal cavity. We report a case of a 32 years-old female patient with familial adenomatous polyposis (FAP), who was already submitted to total colectomy and developed multiple DT, located in the abdominal wall and in the left breast. The patient underwent several surgical procedures, with a multidisciplinary team of surgeons. Wide surgical resections of the left breast and the abdominal wall tumors were performed in separate steps. Polypropylene mesh reconstruction and muscle flaps were needed to cover the defects of the thoracic and abdominal walls. After partial necrosis of the adipose-cutaneous flap in the abdomen that required a new skin graft, she had a satisfactory outcome with complete healing of the surgical incisions. DT is frequent in GS, however, breast localization is very rare, with few cases reported in the literature. Recurrence of DT is not negligible, even after a wide surgical resection. GS patients must be followed up closely, and clinical examination, associated with imaging studies, should be performed to detect any signs of tumor. DT represents one of the most significant causes of the morbidity and mortality that affects FAP patients following colectomy. In general, the surgical procedures to excise DT are highly complex, requiring a multidisciplinary team.

[climacteric Syndrome In A Northeastern Brazilian City: A Household Survey].

To assess the prevalence of Climacteric Syndrome (CS) in women from a municipality of Northeastern Brazil which is less developed socioeconomically. A prospective household survey was performed in São Luís, Maranhão, Brazil with 1,210 climacteric women aged 45 to 60 years. Interviews were applied using previously tested standard questionnaires from April to July 2008. The severity of climacteric symptoms was analyzed by circulatory and psychological indexes and the latter were associated with menopausal status. Multiple correspondence analysis was used to assess the relation among climacteric symptoms. Most patients were 55 to 60 years old (35.3%), mulatto (37.9%), with 9-11 years of schooling (39.8%), with a partner (56%), Catholic (73.9%) and belonged to the socioeconomic class C (51.1%). The prevalence of CS was 85.9%, and hot flashes (56.4%) and sweating (50.4%) were the most prevalent symptoms. The most frequent psychological symptoms were nervousness (45%) and emotional liability (44.8%). The severity of vasomotor and psychological symptoms was significantly higher during the peri and postmenopausal period (p<0.05). Vaginal dryness (62.7%) was the most prevalent urogenital complaint. The prevalence of CS was high among women from São Luís, Maranhão, Brazil.