Síndromes lentiginosos familiares / Family lentiginous syndromes

Los síndromes lentiginosos familiares (SLF)involucran un amplio espectro fenotípico, que abarcadesde una predisposiciónhereditaria a desarrollar lentigos sinenfermedad sistémica hasta un riesgo incrementado en la formación de hamartomas, hiperplasias y otras neoplasias.El prototipo de SLF es el síndrome de Peutz-Jeghers, pero también se incluyen dentro de este grupo de patologías el complejo de Carney, el síndrome LEOPARD, el síndrome de Bannayan-Riley-Ruvalcaba, la enfermedad de Cowden, el síndrome de Laugier-Hunziker, la disección arterial con lentiginosis y las lentiginosis benignas (lentiginosis unilateral parcial y centrofacial).La presencia de lentigos es uno de los hallazgos semiológicos más prominentes en estos cuadros y probablemente, más que una característica clínica asociada, sea el reflejo de la convergencia entre vías de señalización de importancia crucial para la embriogénesis, la diferenciación de la cresta neural, el crecimiento de los órganos diana y el funcionamiento de una amplia gama de tejidos.En el presente trabajo se realiza una descripción detallada de cada uno de los SLF, incluyendo el mecanismo molecular involucrado, las manifestaciones clínicas, la metodología diagnóstica, el seguimiento y el tratamiento.

Familial lentiginosis syndromes involve a broad phenotypic spectrum that includesfrom hereditary predisposition to presentlentigines without systemic disease to the increased risk of hamartomas, hyperplasia and other malignancies development.The prototype is Peutz-Jeghers syndrome, but Carney complex, LEOPARD syndrome, Bannayan-Riley-Ruvalcaba syndrome, Cowden's disease, Laugier-Hunziker syndrome, arterial dissection with lentigines and benign lentiginosis (partial and unilateral centrofaciallentigines) are also included in this group.The presence of lentigines is the most relevant finding and probably more than a clinical feature associated represents a reflection of the convergence of crucial signaling pathways that are important to embryogenesis, differentiation of the neural crest, target organs growth and funcional of a wide range of tissues.In this paper we perform a detailed description of these syndromes, including the molecular mechanisms involved, clinical manifestationsdiagnostic procedures, monitoring, and treatment.

Cowden's Disease Detected by Gastric Polyposis during Endoscopy in a Routine Check Up: A Case Report / 대한소화기내시경학회지

Cowden's disease, a rare autosomal dominant disorder characterized by benign hamartomatous overgrowth of various tissues, increases the risk of cancer of the thyroid, breast, endometrium, prostate, and possibly other organs. Generally, germline mutations in the coding sequence for PTEN are found in 80% of patients with Cowden's disease. Here we report a rare case of incidentally discovered gastric polyposis during esophagogastroscopy for medical screening in a patient with a history of surgery for breast and thyroid cancer. Identifyng the mutation in the PTEN gene to a diagnosis of Cowden's disease.

A case of Cowden's syndrome associated with Lhermitte-Duclos disease / 대한내과학회지

Cowden's disease, or multiple hamartoma syndrome, is an uncommon autosomal dominant condition characterized by mucocutaneous lesions and systemic malignancies. Lhermitte-Duclos disease, or dysplastic gangliocytoma of the cerebellum, is a rare cerebellar lesion that can cause mass effects in the posterior fossa. It may occur sporadically, or in association with Cowden's syndrome. We report a case of Cowden's disease associated with Lhermitte-Duclos disease in a 49-year-old man who underwent a routine checkup

A Case of Cowden's Disease Associated with Breast Cancer / 대한소화기학회지

Cowden's disease, also known as various hamartomatous malformations of multiple organs, is a rare autosomal dominant disorder. The most important feature of Cowden's disease is its frequent association with malignant neoplasm, particularly in the breast and thyroid gland. Cowden's disease with malignant neoplasms, is quite rare in Korea so far. We report a case of Cowden's disease associated with breast cancer in a 41-year-old female who underwent routine health cheek-up.

Identification of a Novel p53 Intronic Mutation in Cowden's Disease

BACKGROUND: Cowden's disease is a rare disorder, characterized by a multiple harmatoma-neoplasia syndrome. Germline mutations in the Phosphatase and Tensin homolog (PTEN) gene have been identified in some individuals with Cowden's disease. The present study aimed to evaluate abnormalities of PTEN and p53 genes in a patient with Cowden's disease. METHODS: Eleven family members including the patient with Cowden's disease were examined in this study. Sequencing analyses were performed on these people and on the normal control group to identify mutation in PTEN and p53 genes. RESULTS: DNA sequencing of PTEN gene showed no mutation in the patient and the family members. The G to C germline mutation was identified only in the patient of Cowden disease at 38th base of intron 2 of p53 gene. CONCLUSIONS: Although the exact role of mutation in p53 gene was not identified in the Cowden's disease, the conformational change of the gene would result in the dysfunction of the tumor suppressor effect of p53 gene. Otherwise, an epigenetic silencing can be a mechanism of disease development in a patient without genetic abnormality.

A Case of Cowden Disease Associated with Lhermitte-Duclos Disease / 대한소화기내시경학회지

Cowden disease (CD), also known as 'multiple hamartoma syndrome', is a rare autosomal dominant disorder with a high risk of breast, thyroid, or genitourinary malignancies. Lhermitte-Duclos Disease (LDD) is believed to be a hamartomatous overgrowth of cerebellar ganglion cells and currently is considered to be a part of CD. However, the report of the association between LDD and CD has been very unusual. We have recently experienced a 53-year-old man with LDD who had acral keratosis of extremities, gastrointestinal polyposis, and multinodular goiter. To our knowledge, it is the second case of CD associated with LDD in Korea. We report it with a review of the literatures.

Lhermitte-Duclos Disease Associated with Cowden Disease

Lhermitte-Duclos disease, or dysplastic gangliocytoma of the cerebellum, is a peculiar hamartoma arising from the cerebellar cortex. Cowden disease, which is also termed as a multiple hamartoma-neoplasia syndrome, is an unusual autosomal dominant disorder characterized by mucocutaneous lesions, including facial papules, gingival papillomas, and acral keratoses. Other systemic hamartomas are frequently present, and there are high incidence of breast, thyroid, and genitourinary malignancies. Recently, it is accepted that Lhermitte-Duclos disease is a part of Cowden disease, a new phakomatosis. Recognition of this association has clinical significance, because diligent long-term follow-up monitoring of individuals with Lhermitte-Duclos disease and Cowden disease may lead to the early detection of malignancy.

Dysplastic Gangliocytoma of Cerebellum(Lhermitte-Duclos Disease): Relation to Cowden Disease

We report a case of dysplastic gangliocytoma of the cerebellum(Lhermitte-Duclos disease) that can cause progressive mass effect in the posterior fossa. Cowden disease is a rare autosomal dominant disorder characterized by mucocutaneous hamartoma and high incidences of systemic malignancies. The patient had no mucocutaneous lesions indicating Cowden disease. With recent advances in molecular genetics, the association between Lhermitte-Duclos disease and Cowden disease has been recognized, it is considered that Cowden disease is a new phakomatosis. Recognition of this association has direct clinical relevance and long term follow up may lead to the early detection of malignancy.

Diagnosis of Cowden's Disease Based on Gastrointestinal Manifestations / 대한소화기내시경학회지

BACKGROUND/AIMS: Cowden's disease is an autosomal dominant hereditary disease characterized by the various hamartomatous and neoplastic lesions of multiple organs. We analyzed gastrointestinal manifestations of 5 cases of Cowden's disease and suggest several findings which are helpful to gastroenterologists for the early diagnosis. METHODS: The clinical characteristics of 5 unrelated patients with Cowden's disease were evaluated. Four patients were male, one patient was female, and their ages at the time diagnosis ranged from 17 to 49 years. All patients had the pathognomonic mucocutaneous lesions and thyroid nodules. RESULTS: In all patients, the esophagus was affected by acanthosis. In 4 patients, the stomach was affected by numerous variable sized polyps. In 4 patients, the duodenum was involved by several polyps. In 4 patients, the entire small bowel and in one patients, only the terminal ileum was affected by numerous polyps. In all patients, the colon, especially the sigmoid colon and rectum, showed numerous variable sized polyps. Family history was positive for stomach cancer in two patients. CONCLUSIONS: Cowden's disease should be considered in patients with esophageal acanthosis among patients with colonic polyposis, although the mucocutaneous lesions, unfamiliar to gastroenterolgists, are pathognomonic criteria for the diagnosis.