[Tooth eruption disturbances and syndromes]. / Eruptiestoornissen en syndromen.

In the tooth eruption mechanism, various disturbances can appear as a result of gene mutations, a consequence of which can be that tooth eruption does not occur. There are 5 syndromes which involve the complete failure of several or even all teeth to erupt, specifically: cleidocranial dysplasia, Gardner's syndrome, osteopetrosis, mucopolysaccharidosis and GAPO syndrome. Some are very rare and will seldom be encountered in a dental practice, but they show how vulnerable the tooth eruption mechanism is. Dentists are generally the ones who identify a tooth eruption problem in a patient. Since syndromes can be associated with other disorders, additional investigation by a clinical geneticist is always important when a syndrome is suspected.

Gardner's syndrome (familial adenomatous polyposis): a cilia-related disorder.

Familial adenomatous polyposis (FAP) is an autosomal dominant form of intestinal polyposis and colorectal cancer caused by germ-line mutations in the adenomatous polyposis coli (APC) gene. The term Gardner's syndrome is used to describe extracolonic manifestations, such as osteomas, skin cysts, congenital hypertrophy of the retinal pigmented epithelium (CHRPE), and desmoid tumours (aggressive fibromatosis), that are especially prominent in families with FAP. We postulate that a ciliary dysfunction is the underlying pathogenetic mechanism of extraintestinal manifestations in patients with FAP. This postulation is based on the presence of common clinical manifestations (ie, cysts, retinal abnormalities, and fibrosis) in Gardner's syndrome and cilia-related disorders. Additionally, both APC and the cilia have degradation of beta-catenin as the common downstream target in the Wnt-signalling pathway. Mutations in APC causing Gardner's syndrome are clustered in a region encoding a series of amino-acid repeats responsible for the binding to beta-catenin. Proofs of principle that beta-catenin could be the key mediator of the ciliary disorder also rely in the findings that overexpression of beta-catenin induces polycystic kidney disease, and CHRPE phenotypes in animal models. Other candidates for the common link between Gardner's syndrome and cilia-related disorders are the APC-binding proteins: end-binding protein 1 (EB1) and kinesin-family-member 3a (KIF3a), both of which are ciliary proteins involved in intraflagellar transport. Finally, pathogenetic similarities between some ciliopathies and extraintestinal tumours in FAP suggest a cilia defect. Understanding extracolonic manifestations in the context of FAP as a ciliary disorder might add new therapeutic options for patients with Gardner's syndrome.

Esteatocistoma múltiplo / Steatocystoma multiplex

O esteatocistoma múltiplo é doença dermatológica rara, caracterizada por lesões múltiplas e de vários tamanhos no tronco. Também podem ser encontradas nas costas, extremidades e escroto. As lesões isoladamente variam de 1mm a 2cm e são macias e móveis. As lesões profundas são da cor da pele; as superfícies normalmente são amarelas. Podem ocorrer isoladas (esteatocistoma simples) ou ser múltiplas (esteatocistoma múltiplo). A doença afeta tanto homens quanto mulheres. Começa no início da vida adulta e persiste indefinidamente. As lesões são usualmente assintomáticas; algumas podem inflamar e supurar, deixando cicatrizes. É uma doença autossômica dominante e associada a um defeito do gene da queratina 17. O principal diagnóstico diferencial inclui cisto epidermóide e cisto veloso eruptivo. Não foi relatada degeneração maligna.

Poliposis familiar hereditaria: a propósito de un caso / Polyposis family hereditary: a purpose of a case

La Poloposis Familiar Hereditaria es un desorden autosómico dominante, caracterizado por la presencia de cientos a miles de pólipos adenomatosos a todo lo largo de la mucosa colónica. La principal causa de muerte es el cáncer colorrectal el cual se presenta en todos los pacientes que no reciben tratamiento preventivo. Presentamos un caso de una paciente femenina de 32 años de edad la cual consultó por presentar rectorragia de 6 meses de evolución. Al examen físico se evidenció un tumor circunferencial a los 3 cm del margen anal, con obstrucción del 80 por ciento de la luz. La colonoscopia reveló la presencia múltiples pólipos de diferentes tamaños desde el margen anal hasta cecoascendente. Se le realizó una colectomía total evolucionando satisfactoriamente. La biopsia reportó un adenocarcinoma bien diferenciado de recto, con infiltración de la serosa y ganglios positivos, y miles de pólipos adenomatosos vellosos, tubulares y túbulovellosos.

Gastrointestinal polyposis syndromes.

Numerous polyposis syndromes involve the gastrointestinal (GI) tract, including both non-hereditary and hereditary types. Causative genes are now known for the seven major syndromes. Genetic and clinicopathologic features are reviewed here and cancer predisposition is emphasized. Genetic testing is available for the GI polyposis syndromes, and can be accessed through GeneTests-GeneClinics on the Internet at http://www.genetests.org/. The website is available at no cost and is a publicly funded medical genetics resource for health care providers and researchers.

Anal sphincter function after intersphincteric resection and stapled ileal pouch-anal anastomosis.

This study was done to determine the effect of the direct ileal pouch-anal anastomosis upon pressure and sensory components of the anal canal and ileal pouch. These findings were related to postoperative continence. Thirty-three patients with ileal pouch-anal anastomosis (25 continent, eight with episodic minor incontinence) were studied 3 +/- 0.3 and 25 +/- 5 months after ileostomy takedown. The maximum resting pressure in the anal canal was significantly lower in patients with an imperfect result (35 +/- 5 mm Hg) than in continent patients (44 +/- 5 mm Hg) (P less than 0.05). Postoperatively the maximum squeeze anal pressure was slightly greater in continent than in incontinent patients (99 +/- 8 mm Hg vs. 87 +/- 7 mm Hg) (P greater than 0.05). The postoperative recto-(ileo-)anal inhibitory reflex was present in 27 percent. The linear correlation between strength of rectal (ileal) distension and depth resp. duration of internal sphincter relaxation as preoperatively observed disappeared postoperatively in every group of patients. Simultaneous measurements of pouch and anal pressure in patients with imperfect results revealed a reduced positive pouch anal pressure gradient compared to the continent group. This low pouch-anal pressure gradient is thought to be responsible for the increased incidence of soiling in some of our patients.

Mesenteric fibromatosis presenting with ascites in childhood.

A 7-year-old boy presented with acute ascites due to mesenteric fibromatosis. The pathophysiological mechanisms for formation of ascitic fluid and some aspects of the aetiology of intra-abdominal fibromatosis and its association with Gardener's syndrome are discussed.

Ophthalmologic and electro-oculographic findings in Gardner's syndrome.

We examined six patients with Gardner's syndrome, eight first-degree relatives, and 31 age- and sex-matched controls to document the presence, distribution, and morphologic features of congenital hypertrophy of the retinal pigment epithelium. Patients with Gardner's syndrome had multiple, bilateral lesions, with 288 of 346 foci (83%) located posterior to the equator. Linear-shaped congenital hypertrophy of the retinal pigment epithelium, a distinctive finding in these patients, accounted for 44 of 140 large lesions (31%). Despite multifocal fundus involvement, results of electro-oculography were normal in all eyes tested.

The desmoid syndrome. New aspects in the cause, pathogenesis and treatment of the desmoid tumor.

Based on a detailed clinical and laboratory investigation of 89 patients with histologically verified desmoid tumor and the pertinent medical literature, we have reviewed the etiologic factors, clinical characteristics, and results of treatment of this rare disorder. The incidence of the tumor in the Finnish population is low, 2.4 to 4.3 new cases per 10(6) inhabitants per year. The age distribution profile demonstrated four distinct peak periods: the juvenile period, the fertile period, the middle-age period and the old-age period. The juvenile desmoid tumor is an extraabdominal tumor found in young girls, the fertile variety is an abdominal tumor found in women, the middle age variety is also overwhelmingly abdominal but the sex ratio approaches equality, whereas in the old age group, both abdominal and extraabdominal tumors are equally frequent and the sex ratio is equal. In all male patients, the growth rate was low. A low growth rate was also recorded in young girls. A growth rate of twice that speed was seen in fertile women and four times that speed in the middle age group. In the old age group, a low growth rate, equal to that of male patients, was a rule. The fertile female patients with desmoid tumor had a significant predisposition to estrogen dominance and deviation from progesterone dominance. The direct relationship of the growth rate to the level of endogenous estrogen in the female patients and the demonstration of significant amounts of estradiol but not progesterone receptors in the tumor cytosol further suggest that the growth rate of desmoid tumor is regulated by steroid sex hormones. A significant number of patients with an abdominal desmoid tumor had a history of surgical trauma in the region of subsequent tumor growth. A very high number of the patients demonstrated multiple minor malformations of the bony skeleton. An increased frequency of these malformations was also recorded in the families of the patients and the distribution of the malformations among the family members was compatible with an autosomally dominant pattern of inheritance. After operation, the frequency of recurrence was not statistically different, regardless of whether the tumor was completely removed or not. A combination of operation and radiotherapy did not reduce the frequency of recurrences; in fact, it doubled it.(ABSTRACT TRUNCATED AT 400 WORDS)

Classification and risk assessment of individuals with familial polyposis, Gardner's syndrome, and familial non-polyposis colon cancer from [3H]thymidine labeling patterns in colonic epithelial cells.

A probabilistic analysis has been developed to assist the binary classification and risk assessment of members of familial colon cancer kindreds. The analysis is based on the microautoradiographic observation of [3H]thymidine-labeled epithelial cells in colonic mucosa of the kindred members. From biopsies of colonic mucosa which are labeled with [3H]thymidine in vitro, the degree of similarity of each subject's cell-labeling pattern measured over entire crypts was automatically compared to the labeling patterns of high-risk and low-risk reference populations. Each individual was then presumptively classified and assigned to one of the reference populations, and a degree of risk for the classification was provided. In carrying out the analysis, a linear score was calculated for each individual relative to each of the reference populations, and the classification was based on the polarity of the score difference; the degree of risk was then quantitated from the magnitude of the score difference. When the method was applied to kindreds having either familial polyposis or familial non-polyposis colon cancer, it effectively segregated individuals affected with disease from others at low risk, with sensitivity and specificity ranging from 71 to 92%. Further application of the method to asymptomatic family members believed to be at 50% risk on the basis of pedigree evaluation revealed a biomodal distribution to nearly zero or full risk. The accuracy and simplicity of this approach and its capability of revealing early stages of abnormal colonic epithelial cell development indicate potential for preclinical screening of subjects at risk in cancer-prone kindreds and for assisting the analysis of modes of inheritance.