Co-Inheritance of Autosomal Dominant Polycystic Kidney Disease and Naevoid Basal Cell Carcinoma Syndrome: Effects on Renal Progression.

The calcium signalling and hedgehog (HH) signalling pathways operate in the primary cilium. Abnormalities in these pathways cause autosomal dominant polycystic kidney disease (ADPKD) and naevoid basal cell carcinoma syndrome (NBCCS) respectively. Several reports have proposed that hyperactivation of the HH pathway in animal models of polycystic kidney disease affects normal renal development and renal cyst phenotype. A family with 2 cases (a proband and her sister) of ADPKD and NBCCS coinheritance led us to investigate whether interactions may be present in the 2 pathways. The effect of HH pathway hyperactivation (due to c.573C>G mutation on PTCH1 gene that cause NBCCS) on renal ADPKD progression in the proband was compared to 18 age- and sex-matched ADPKD patients in a 9-year, prospective, follow-up study. Blood pressure, total kidney volume, estimated glomerular filtration rate, plasma copeptin, urine excretion of albumin, total protein and monocyte chemoattractant protein-1 (MCP-1) were analysed. Data for the sibling was not available. In the ADPKD group, blood pressure and estimated glomerular filtration rate were within normal values, and total kidney volume and MCP-1 increased (p < 0.01) throughout the study. In comparison, during the 9-year follow-up, the proband showed persistent hypertension (from 125/85 to 140/95 mm Hg), low total kidney volume (75 and 61% of median ADPKD), and a ninefold increase in urine MCP-1. We found no differences in urine excretion of albumin or plasma copeptin values. These results suggest that HH hyperactivation may play a minimal role in ADPKD progression. These observations can help to clarify the clinical impact of affected pathways in renal development and cystogenesis in humans.

The Gorlin-Goltz Syndrome: diagnosis of a case associated with heart disease and type 2 diabetes mellitus / Síndrome de Gorlin-Goltz: diagnóstico de um caso associado à cardiopatia e diabetes mellitus 2

The Gorlin-Goltz syndrome (GGS) is a hereditary, autosomal dominant condition, with high penetrance and variable expressivity, resulting from mutations in the genes PTCH1, PTCH2, or SUFU. The diagnosis is based on the presence of 2 major criteria or a major criterion associated with 2 minor criteria, including multiple basal cell carcinomas, keratocystic odontogenic tumor (KOT), and bifid rib. Other endocrine, neurological, ophthalmologic, genital, respiratory, and cardiovascular alterations are found in the literature, but with variable manifestations. This study reports the case of a patient diagnosed with GGS associated with diastolic congestive heart failure and type 2 diabetes mellitus, who underwent multiple treatments for components of the syndrome. More recently, the patient underwent decompression followed by cystic enucleation of two KOTs in the jaw, oral rehabilitation with removable prosthodontics, cardiological evaluation, and attempted clinical control of endocrine and cardiac problems.

A síndrome de Gorlin-Goltz (SGG) é uma condição hereditária, autossômica dominante, com alta penetrância e expressividade variável, decorrente de mutações nos genes PTCH1, PTCH2 ou SUFU. O diagnóstico é baseado na presença de dois critérios maiores ou um critério maior associado a dois critérios menores, dentre eles múltiplos carcinomas basocelulares, tumor odontogênico ceratocístico (TOC) e costela bífida. Outras alterações endócrinas, neurológicas, oftalmológicas, genitais, respiratórias e cardiovasculares são encontradas na literatura, porém com manifestações variáveis. O objetivo deste trabalho é relatar um caso clínico de uma paciente sistematicamente diagnosticada com SGG associada à insuficiência cardíaca congestiva diastólica e diabetes mellitus 2 submetida a tratamentos seriados das respectivas manifestações sindrômicas. Mais recentemente, à descompressão cística seguida da enucleação de dois TOC em mandíbula, reabilitação oral com prótese total removível, avaliação cardiológica e tentativa de controle clínico das alterações endócrinas e cardíacas.

Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital teratoma, caused by a PTCH1 frameshift mutation.

Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a high level of penetrance and variable expressivity. The syndrome is characterized by developmental abnormalities or neoplasms and is diagnosed with 2 major criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical manifestation associated with this syndrome in a boy affected by NBCCS who had congenital orbital teratoma at birth. Later, at the age of 15 years, he presented with 4 major and 4 minor criteria of NBCCS, including multiple basal cell carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology, more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis. PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA. This mutation generated a frameshift within exon 2 and an early premature stop codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of function. Identification of this mutation is useful for genetic counseling. Although the clinical symptoms are well-known, our case contributes to the understanding of phenotypic variability in NBCCS, highlighting that PTCH1 mutations cannot be used for predicting disease burden and reinforces the need of a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS patients.

Gorlin-Goltz syndrome: case report and review of literature

Description of a case report of Gorlin-Goltz Syndrome diagnosed in a male newborn who presented increased head circumference and bifid ribs. Mother and grandmother presented typical physical findings of the syndrome, including palmar pits, odontogenic cysts, and history of multiple skin cancer resections. The diagnosis was based on clinical findings of three relatives. A literature review is also presented.

Retrospective study of 25 cases of keratocystic odontogenic tumor: epidemiology and treatment.

AIM: Keratocystic odontogenic tumor (KOT) is a benign odontogenic neoplasm with locally aggressive behavior and high recurrence rates. It is associated with nevoid basal cell carcinoma syndrome which usually has a more rapid growth. The aim of the study is to report the experience of our service on diagnosis and treatment of KOT. MATERIALS AND METHODS: Twenty-five cases of KOT were diagnosed between the years of 1989 and 2006. Demographic data was collected as well as diagnose and treatment. RESULTS: Fifty-six percent were female with a mean age of 33 years old. Seventy percent occurred in mandibula and all received surgical treatment, associate or not with adjuvant therapy, such as cryotherapy and Carnoy's solution. Recidive was observed in 48% of cases with a mean period of time of 18 months. CONCLUSION: Our data analysis showed the importance of previous diagnosis before enucleation procedure and long-term follow-up for recurrence early detection. Recurrence incidence is more frequent on first year after diagnosis. CLINICAL SIGNIFICANCE: KOT is a benign tumor with local aggressive behavior and therefore its treatment must consider the high index of recidive. Reports of protocol treatment should raise new discussion to decrease recurrence rates.

Queratoquistes múltiples, reporte de un caso familiar / Multiple keratocysts, report of a familial case

El artículo describió a tres miembros de una familia, que presentaron queratoquistes odontogénicos múltiples; posterior a los tratamientos quirúrgicos se presentaron dos recurrencias a un seguimiento de 6 años. Se diagnosticó el síndrome del carcinoma del nevo basocelular o síndrome de Gorlin y Goltz en estos tres pacientes, porque presentaron además nevos múltiples, defectos de fusión en vértebras cervicales y calcificación de la hoz del cerebro

[Hypogonadism caused by Gorlin-Goltz syndrome]. / Hipogonadismo causado por el síndrome de Gorlin-Goltz.

The Gorlin-Goltz syndrome is a dominant autosomic disorder characterized by cancerigenic predisposition and multiple development defects, apparently without reproductive compromise. The complex is characterized by four primary symptoms, which include nevoid basal cell epitheliomas malignantly prone, keratocystic jaw, skeletal abnormalities and intracranial calcifications. Apparently, reproductive problems reported had been rarely associated with this syndrome. We present the case of a patient with clinic stigmatae of Gorlin-Goltz syndrome, who had a characteristic progress as seen in the literature; he was the fifth product of a 43 year-old female (father was 48 years old); who at birth disclosed right eye microftalmy, bilateral cryptorchidism surgically treated at age of six. At puberty, an odontogenic cyst of the jaw was noted and enucleated. He also showed facial nevi in neck, thorax and abdomen. When he was admitted being 14 years old in our clinic, he had recurrent bilateral cryptorchidism, sexual immatturity and infertility. It is important to take into consideration Gorlin-Goltz stigmatae in cases of hypogonadism in order to recognize a further genetic influence.

Síndrome de Goltz-Gorlin: relato de caso / The Goltz-Gorlin syndrome: a case report

Objetivo: descrever a particularidades de um caso de Síndrome de Goltz-Gorlin. Descrição: uma menina de três anos e quatro meses de idade foi encaminhada para a fisioterapia. Os achados clínicos de agenesia óssea, assimetria de membros inferiores, sindactilia, lábio leporino, orelhas de formação rudimentar, assimetria da face, hiperpigmentação...

Síndrome de nevo basocelular / Basal cell nevus syndrome

Se presenta un caso clínico de cáncer basocelular múltiple en un paciente de 36 años sin antecedentes familiares de enfermedades cutáneas o neoplásicas. La lesión está ubicada en la región facial, cuero cabelludo y tórax. Fue tratado quirúrgicamente con resección en paños de la piel y reparando con injertos dermoepidérmicos

Comparative study of keratocysts, associated and non-associated with nevoid basal cell carcinoma syndrome.

Keratocysts of the solitary type were histologically and histometrically compared with those associated with the nevoid basal cell carcinoma syndrome (NBS). It was observed that parakeratinization, intramural epithelial remnants and satellite cysts were a more frequent finding among NBS keratocysts than among solitary keratocysts. Conversely, it was also found that the total nuclear density was greater in non-associated cysts and that the total number of nuclei, the number of basal nuclei and the epithelial height values were also higher in solitary keratocysts. NBS-keratocysts and solitary keratocysts are considered to be two morphologically distinct populations of the same entity.