1/142. Severe Lhermitte-Duclos disease with unique germline mutation of PTEN. Germline mutations in the PTEN gene have recently been identified in some individuals with Cowden disease (CD), Lhermitte-Duclos disease (LDD), and Bannayan-Zonana syndrome. We report on a patient with CD and LDD in whom a unique de novo germline missense mutation is present in the PTEN gene. Direct sequence analysis detected a transitional change (T-->C) at nucleotide 335, resulting in substitution of the amino acid proline for leucine. The mutation is in exon 5, which has been proposed as a "hot-spot" for germline mutations. Comparison of this patient's clinical course with the previously reported cases of CD and LDD shows more extensive and more severe clinical findings than reported previously. Findings in this patient contribute to the current understanding of germline PTEN mutations and clinical outcome. ( info) |
2/142. Identification of a novel PTEN mutation (L139X) in a patient with Cowden disease and sjogren's syndrome. Cowden disease is an autosomal dominant disorder associated with an increased risk of breast, thyroid, and skin cancer in which germline mutations in a candidate tumour suppressor gene (PTEN) have been identified previously. sjogren's syndrome is a chronic inflammatory and autoimmune disorder of exocrine glands for which the genetic basis is unknown. This report describes a novel PTEN mutation (L139X) in a patient with Cowden disease and sjogren's syndrome. This observation raises the possibility of a link between mutations in the PTEN gene and sjogren's syndrome. ( info) |
3/142. Lhermitte-Duclos disease as a component of Cowden's syndrome. Case report and review of the literature. In recent years, 16 cases involving the association between Lhermitte-Duclos disease (LDD), which is a hamartomatous overgrowth of cerebellar tissue, and Cowden's syndrome (CS), an autosomal-dominant condition characterized by multiple hamartomas and neoplasias, have been reported. LDD may be one of the manifestations of CS. Recently, mutations of the PTEN/MMAC 1 gene, a tumor suppressor gene, have been found in families with CS, including four patients in whom LDD was diagnosed. The authors present a case of LDD in a 53-year-old woman who also had the typical mucocutaneous lesions found in CS, as well as goiter and intestinal polyposis. In this case, CS had never been suspected until the diagnosis of LDD was made. The mutation detected in the PTEN/MMAC 1 gene as well as neuropathological results are described. ( info) |
4/142. Dysplastic gangliocytoma (Lhermitte-Duclos disease) associated with Cowden disease: report of a case and review of the literature for the genetic relationship between the two diseases. We report a case of dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease, LDD). The patient also had cutaneous and mucosal hamartomas, adenomatous goiter, bilateral breast tumors, and gastrointestinal polyposis, indicating the diagnosis of Cowden disease (CD), the familial hamartoma syndrome. This was a rare sporadic case without any family history of CD, though CD is considered to be an autosomal dominant hereditary disease. Based on a thorough review of the previously reported cases, it is reasonable to consider that CD is inherited in autosomal dominant fashion through a CD gene (PTEN) containing a germline mutation, and that the occurrence of LDD is predicted on an additional somatic hit on the remaining normal CD allele or another unknown gene. ( info) |
5/142. Arteriovenous and lymphatic malformations, linear verrucous epidermal nevus and mild overgrowth: another hamartoneoplastic syndrome? We report a 22 year old female presenting with slowly progressive paraparesis, who appeared to have many (mainly subcutaneous) hamartomas. The neurological symptoms were caused by intraspinal masses and arteriovenous malformations. In addition, she had mild overgrowth of one leg and lymph vessel malformations. This combination of symptoms resembles proteus syndrome, but is different in symptomatology and progression and may be yet another hamartoneoplastic syndrome. ( info) |
6/142. Multiple chondromatous hamartomas of the lung: a case report and review of the literature with special reference to Carney syndrome. BACKGROUND: Multiple chondromatous hamartomas of the lung, which are very rare, are a feature of Carney syndrome. The relation between the two entities is not clear. methods: A patient with multiple chondromatous hamartomas of the lung is described in this article. The literature was reviewed with special reference to the relation between multiple chondromatous hamartomas of the lung and Carney syndrome as well as the triad of gastric epithelioid leiomyosarcoma, functioning extra-adrenal paraganglioma, and pulmonary chondroma. RESULTS: A total of 15 cases of multiple chondromatous hamartomas of the lung have been published worldwide. Two cases exhibited two other features of Carney syndrome, namely, gastric leiomyogenic neoplasms and extra-adrenal paragangliomas, and three other cases demonstrated only gastric leiomyomatous neoplasms. These five patients were all young females. CONCLUSIONS: Some patients with multiple chondromatous hamartomas of the lung have a history of Carney syndrome. patients with multiple chondromatous hamartomas require further examination of other sites, particularly the stomach and nervous system. ( info) |
| A patient with Cowden disease and multiple arteriovenous malformations (AVMs) that resulted in high output heart failure is described. Cowden disease is a familial syndrome characterized by endodermal, mesodermal and ectodermal dysplasia causing benign and malignant tumors of the skin, breast, gastrointestinal tract, and thyroid gland. Our patient had gastrointestinal polyposis, a right renal tumor, a left lung tumor, an adenomatous goiter, and typical dermatologic findings such as facial papules, acral keratosis, gingival papillomatosis and hemangiomas. AVMs were observed in the pelvis, cervical vertebra, liver, and right supraclavicular area. Transcatheter embolization was performed 7 times for the pelvic AVMs, but the effect decreased with repetition and the patient died of heart failure 2 years after the first embolization. The serum levels of tissue plasminogen activator (t-PA), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta1 were high, suggesting that these angiogenic molecules may play a role in the pathogenesis of AVMs in Cowden disease. ( info) |
8/142. retinoblastoma with acute lymphoblastic leukemia, polyposis coli, and multiple hamartomas. It has long been recognized that compared with their age- and sex-matched controls, survivors of hereditary retinoblastoma have a considerably higher risk of the development of second malignancies (10% at 20 years and 15% at 30 years of follow-up), including osteosarcoma, leiomyosarcoma, melanoma, fibrosarcoma, and other rare spindle cell sarcomas. patients with the nongenetic variety of retinoblastoma do not particularly seem to have an increased incidence of other malignancies than the general population. However, it should be noted that a child with unilateral disease carries a 15% chance of having germline mutation. The cumulative mortality rate from second malignancies was 1.5% at 40 years after unilateral retinoblastoma diagnosis and 26% for bilateral cases in a large survey of 1458 patients. A child with unilateral retinoblastoma, cafe au lait spots, hairy nevus, and grouped pigmentation of retina in the fellow eye is described who furthermore developed acute leukemia and polyposis coli. ( info) |
9/142. Pulmonary abnormalities in Cowden's disease. Cowden's disease is an inheritable multiple neoplastic syndrome represented by benign and malignant lesions of skin, digestive tract, mucosae, breast and thyroid. The syndrome, first described by Lloyd and Dennis in 1963, includes benign lung lesions, described in the literature only as hamartomas. The unusual condition of our case consists of multiple and bilateral lipomatous lesions of the lung and of adipose colonic polyps, diagnosed respectively by video assisted mini-thoracotomy and by endoscopic biopsies. ( info) |
10/142. An overlap of Cowden's disease and Bannayan-Riley-Ruvalcaba syndrome in the same family. We describe a family with the unusual association of Cowden's disease and Bannayan-Riley-Ruvalcaba syndrome. The father has characteristic mucocutaneous features that are palmoplantar keratoses, multiple facial papules, oral papillomatoses, lipomas, and vitiligo with involvement of the thyroid and digestive tract. The son presents with pigmented macules of the penis, macrocephaly, and a lipoma that are typical for Bannaya-Riley-Ruvalcaba syndrome. Recent studies have demonstrated that these 2 diseases are allelic disorders at the PTEN locus on chromosome 10q. ( info) |