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 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The medical care of patients affected by rare disorders depends heavily on experiences garnered from prior cases, including those patients evaluated by the treating physician and those published in the medical literature. The utility of published cases is wholly dependent upon accurate diagnosis of those patients. In our experience, the rate of misdiagnosis in Proteus syndrome (PS) is high. Diagnostic criteria have been published, but these criteria have not been applied consistently and were published after many case reports appeared in the literature. We reviewed 205 cases of individuals reported to have PS in the literature and three of us independently applied the diagnostic criteria to these case reports. Our initial diagnostic congruence was 97.1% (199/205); the discrepancies in six cases were easily resolved. Only 97 (47.3%) of reported cases met the diagnostic criteria for PS; 80 cases (39%) clearly did not meet the criteria; and although 28 cases (13.7%) had features suggestive of PS, there were insufficient clinical data to make a diagnosis. Reported cases that met the PS criteria had a higher incidence of premature death, and other complications (scoliosis, megaspondyly, central nervous system abnormalities, tumors, otolaryngologic complications, pulmonary cystic malformations, dental and ophthalmogic complications) compared to those in the non-Proteus group. The cases that met the criteria were more often male, which has implications for hypotheses regarding the etiology and pathophysiology of PS. We also studied the attributes that led authors to conclude the reported patients had PS when we concluded they did not. We found that two of the diagnostic criteria (disproportionate overgrowth and connective tissue nevi) were often misinterpreted. In PS, the abnormal growth is asymmetric, distorting, relentless, and occurred at a faster rate compared to the rest of the body. Furthermore, PS was associated with irregular and disorganized bone, including hyperostoses, hyperproliferation of osteoid with variable calcification, calcified connective tissue, and elongation of long bones with abnormal thinning. In contrast, non-Proteus cases displayed overgrowth that was asymmetric but grew at a rate similar to the growth found in unaffected areas of the body. Also, the overgrowth in non-Proteus cases was associated with normal or enlarged bones together with ballooning of the overlying soft tissues. Taken together, these data show that (1) PS diagnostic criteria sort individuals with asymmetric overgrowth into distinct groups; (2) individuals with PS were more likely to have serious complications; (3) PS affects more males than females; and 4) the published diagnostic criteria are useful for clinical care and research. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html.
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PMID:Reassessment of the Proteus syndrome literature: application of diagnostic criteria to published cases. 1537 14

Proteus syndrome is a complex disorder consisting variably of disproportionate, asymmetric overgrowth of body parts; cerebriform connective tissue nevi; epidermal nevi; vascular malformations of the capillary, venous, and lymphatic types; and dysregulated adipose tissue. Serious complications may ensue, such as pulmonary embolism, cystic lung disease, and various neoplasms. Somatic mosaicism, lethal in the nonmosaic state, is the best working hypothesis. Although Proteus syndrome data are consistent with this hypothesis, it has not been proven. The etiology is unknown to date. Diagnostic criteria are emphasized because misdiagnosis of Proteus syndrome is common. Finally, evaluation and management are discussed.
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PMID:Proteus syndrome: an update. 1601 Jun 81

Proteus syndrome is a rare, sporadic genetic disorder characterized by overgrowth of multiple different tissues in a mosaic pattern. It is associated with connective tissue nevi, epidermal nevi, disproportionate overgrowth of multiple tissues, vascular malformations, characteristic tumors, and specific facial anomalies. Joseph Merrick, popularly known as the Elephant Man, is now believed to have suffered from Proteus syndrome. A case of Proteus syndrome and associated findings on bone scintigraphy are presented.
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PMID:Proteus syndrome: a rare cause of hemihypertrophy and macrodactyly on bone scanning. 1610 Apr 77

Proteus syndrome is a variable and complex disorder characterized by multifocal overgrowths affecting any tissue or structure of the body. We present a girl aged 3 years and 8 months with an epidermal nevus, port-wine stain, macrodactyly with gigantism of the feet, lymphohemagiomas and multiple lipomas.
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PMID:Proteus syndrome. 1639 65

A patient with Proteus syndrome presented with lower gastrointestinal bleeding due to multiple colonic hemangiomas, a finding which has not been described previously in this syndrome. The patient was a 20-year-old man with features fulfilling the diagnostic criteria for Proteus syndrome. He fulfilled both general criteria (mosaic distribution of the lesions, progressive course and sporadic occurrence) and specific criteria (including epidermal nevus, disproportionate overgrowth of limbs and vascular malformations). Fiberoptic colonoscopy revealed multiple hemangiomas, 0.5-1 cm in diameter, on the left side of the colon. Some gastrointestinal complications have been reported in patients with Proteus syndrome, including rectal polyps, colonic lipomatosis, atrophy of the intestinal villi and intestinal affection with fatty wall thickening but, as far as we are aware, colonic hemangiomas have not previously been reported in this syndrome.
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PMID:A new gastrointestinal finding in Proteus syndrome: report of a case of multiple colonic hemangiomas. 1644 5

A 3-year-old boy with Proteus syndrome has a novel germline p.Y68D mutation of the PTEN gene inherited from his mother who has Cowden syndrome. In addition, DNA extracted from curettings of his widespread epidermal naevus shows loss of heterozygosity for this mutation. To our knowledge, this has not been described before.
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PMID:Epidermal naevus in Proteus syndrome showing loss of heterozygosity for an inherited PTEN mutation. 1799 97

In the 26th year of life a young woman suffered a portal and mesenteric thrombosis followed by portal hypertension with splenomegaly, esophageal varices and pancytopenia. After splenorenal shunt surgery and splenectomy hematologic parameters resolved rapidly. Also, she was suffering of Proteus syndrome, which is an extremely rare and sporadic hamartomatous disorder characterized by a variety of cutaneous and subcutaneous tumors including vascular malformations, several types of nevi, partial gigantism of the hands and/or feet and cystic visceral affections. It has been demonstrated that concurrence of several prothrombotic risk factors occur relatively often in patients with portal vein thrombosis. An extensive investigation of thrombophilic factors revealed reproduced high anti-beta2-glycoprotein I antibody titers together with mildly increased homocysteine levels. Other coagulation parameters were normal or negative. The presence of myeloproliferative moglobinuria was ruled out. Together with the history of recurrent superficial thrombophlebitis and portal vein thrombosis in the absence of other underlying diseases allowed for diagnosis of primary antiphospholipid syndrome being aggravated by hyperhomocysteinemia and vascular malformations caused by Proteus syndrome. Because of combined risk factors for further thrombembolisms permanent oral anticoagulant therapy was initiated.
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PMID:[A young patient with portal and mesenteric vein thrombosis and Proteus syndrome]. 1675 42

Proteus syndrome (PS) is a severe, variable, and rare disorder with asymmetric and disproportionate overgrowth of body parts, cerebriform connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. It is associated with benign and occasionally malignant tumors. We report the first case of ductal carcinoma in situ (DCIS) in a 28-yr-old woman with PS who underwent a mastectomy for asymmetric overgrowth. The cut surface of the tissue showed a discrete, white, lobulated, solid mass with multiple cysts with occasional small polypoid nodules. Microscopically, the tissue was characterized by neoplastic and non-neoplastic changes. The former consisted of multiple intraductal papillomas and low-grade intraductal papillary, solid, and cribriform carcinoma. The non-neoplastic changes were characterized by cysts of various sizes, lined by cuboidal or apocrine cells, focally with epithelial papillary proliferation; the lumens contained eosinophilic, mucicarmine-positive, and PAS-positive material. Variable ductal proliferation and periductal, peri- and intra-lobular fibrosis with loose fibrous connective tissue was present. The carcinoma was positive for ER, PR, CK7, and MIB-1 (40%), and negative for p53 and CK20 staining. We conclude that DCIS may be one of the tumors associated with PS and that the proliferative phenotype serves as an initiator for carcinogenesis. This case highlights the difficulty of recognizing small foci of carcinoma in an asymmetrical overgrowth of the breast in a young woman with PS.
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PMID:Morphological characterization of the breast in Proteus syndrome complicated by ductal carcinoma in situ. 1712 37

Within the group of epidermal nevi, a so far nameless disorder is described under the term "linear Cowden nevus". This non-organoid epidermal nevus is caused by loss of heterozygosity, occurring at an early developmental stage in an embryo with a germline PTEN mutation, giving rise to Cowden disease. Hence, linear Cowden nevus can be categorized as a characteristic feature of type 2 segmental Cowden disease. Until now, several authors had mistaken this epidermal nevus as a manifestation of Proteus syndrome. The concept of linear Cowden nevus implies that Proteus syndrome is by no means caused by PTEN mutations. As a clinical difference, linear Cowden nevus is markedly papillomatous and thick, whereas linear Proteus nevus tends to be rather flat. Moreover, the spectrum of possibly associated cutaneous or extracutaneous anomalies differs in the two types of nevi. In conclusion, linear Cowden nevus, that may also be called "linear PTEN nevus", represents a distinct clinicogenetic entity.
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PMID:Linear Cowden nevus: a new distinct epidermal nevus. 1733 96

We describe two patients from distinct Cowden disease families with specific germline PTEN mutations whose disease differs from the usual appearance of Cowden disease. Their phenotype associates classical manifestations of Cowden disease and congenital dysmorphisms including segmental overgrowth, arteriovenous and lymphatic vascular malformations, lipomatosis and linear epidermal nevus reminiscent of the diagnosis of Proteus syndrome. We provide evidence in one of the two patients of a secondary molecular event: a loss of the PTEN wild-type allele, restricted to the atypical lesions that may explain an overgrowth of the affected tissues and the atypical phenotype. These data provide a new demonstration of the Happle hypothesis to explain some segmental exacerbation of autosomal-dominant disorders. They also show that a bi-allelic inactivation of PTEN can lead to developmental anomalies instead of malignant transformation, thus raising the question of the limitations of the tumor suppressive function in this gene. Finally, we suggest using the term 'SOLAMEN syndrome' (Segmental Overgrowth, Lipomatosis, Arteriovenous Malformation and Epidermal Nevus) in these peculiar situations to help the difficult distinction between the phenotype of our patients and Proteus syndrome.
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PMID:Segmental overgrowth, lipomatosis, arteriovenous malformation and epidermal nevus (SOLAMEN) syndrome is related to mosaic PTEN nullizygosity. 1739 3


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