1/12. Three hong kong Chinese cases of pretibial epidermolysis bullosa: a genodermatosis that can masquerade as an acquired inflammatory disease.Three patients in two families presented with many years' history of fragile skin, blisters, erosions and scars affecting almost exclusively the shin areas, accompanied by a variable degree of itching. Two of the patients also had toenail dystrophy. skin biopsy revealed dermal-epidermal blister formation and milia but no immunohistochemical evidence of immunoglobulin or complement deposition. Electron microscopic study of the lesional and perilesional skin showed very sparse or absent anchoring fibrils. Immunolabelling for type VII collagen using LH 7.2 monoclonal antibody revealed a bright, linear staining pattern at the dermal-epidermal junction. The clinicopathological features were thus compatible with pretibial epidermolysis bullosa, a subtype of dystrophic epidermolysis bullosa. Of note, the inflammatory nature of the skin lesions, and their resemblance to nodular prurigo and hypertrophic lichen planus, had caused diagnostic difficulties in all cases in the past. A high degree of awareness of this rare subtype of epidermolysis bullosa is important to establish the correct diagnosis, to allow for genetic counselling and to plan clinical management.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
2/12. risk in numbers--difficulties in the transformation of genetic knowledge from research to people--the case of hereditary cancer.Difficulties in communicating diagnostic information are exacerbated when the 'diagnosis' is a 'genetic risk' for cancer. The risk estimation demanded in this situation differs from other types of probability estimations. Observations of participants in 45 consultation sessions between physicians and potential patients were conducted at a clinic for hereditary cancer to explore the communication of genetic information. Thirty-three sessions were audiotaped, transcribed verbatim and analyzed, along with notes from the other sessions. A dominant theme was found to be numerical discussion of risk. Further analysis resulted in the description of problems for practitioners in the process of translating scientific knowledge into clinical management. Problems in providing information include unclear aims of the consultation sessions, mixing various types of background information and probabilities, recognizing how low the predictive values are, and difficulties in communicating the relationship between probability and conclusions. Problems in communicating information about the genetic risk for cancer are of at least two types: dilemmas arising from uncertainties implicit in the nature of the information itself and difficulties in communicating information in a manner that those concerned can interpret. These issues need clarification, so that information with far-reaching consequences can be made as clear and comprehensible as possible for those involved.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
3/12. growth retardation and osteomalacia as a result of ifosfamide nephrotoxicity in a 3-year-old boy whose genotype reveals the genes encoding glutathione S-transferases GSTM1 and GSTT1.A case of a child with growth retardation and prolonged osteomalacia, as a result of chronic renal tubulopathy, following successful therapy for a sacral-coccygeal germinal tumour, is described. The male patient was enrolled into the research programme for the evaluation of the association between deletion of the genes encoding a number of classes of glutathione S-transferases (GST) and adverse reactions to alkylating agents. His genotype revealed the genes encoding glutathione transferase classes GSTM1 and GSTT1, but these enzymes did not provide adequate protection for the tubular cells, from the toxic effects of ifosfamide metabolites. Intense chemotherapy resulted in an increased risk of chronic side effects. Further studies are necessary for increased understanding of the inter-individual variability in the extent and nature of ifosfamide nephrotoxicity.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
4/12. Medical genetics: 1. Clinical teratology in the age of genomics.Teratogenic exposures are those that can cause an embryo or fetus to develop abnormally. Several factors determine whether an agent is teratogenic, including the gestational timing of the exposure, as well as the dose, route and nature of the agent itself. We review the general concepts of teratogenesis, as well as known genetic susceptibilities to teratogenic effects, with a special focus on antiepileptic drugs. We discuss general principles of risk counselling and risk reduction, and we describe several long-known teratogens, as well as several exposures recognized only recently to have teratogenic potential.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
5/12. Limb-body wall complex: a case series.OBJECTIVE: Limb-body wall complex (LBWC) is a rare fetal polymalformation of uncertain etiology, but it has been regarded as sporadic in nature with a low recurrence risk. We review a case series in light of recent evidence about possible genetic and environmental associations. methods: All abortions or births coded as limb-body wall defect or fetal acrania/exencephaly or with unclassified polymalformation between January 1996 and January 2001 were audited. RESULTS: During the 5-year period there were 33,286 live births in our region. Eleven cases met the criteria of LBWC giving an incidence of 0.33/1000 live births. In 50%, 50% and 30% of women a history of cigarette, alcohol and marijuana use, respectively, was noted. Furthermore, 40% of the women had a history of a previous infant with a congenital anomaly. One patient delivered two consecutive male infants with LBWC. CONCLUSIONS: Whilst the majority of cases of LBWC are sporadic, some women may have an underlying genetic predisposition. It may be prudent to advise against the use of alcohol, cigarettes and other drugs and to offer an ultrasound scan in a tertiary referral center in a subsequent pregnancy.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
6/12. Late-onset apparent mineralocorticoid excess caused by novel compound heterozygous mutations in the HSD11B2 gene.Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, 11beta-HSD2 (HSD11B2), explain the molecular basis for the syndrome of apparent mineralocorticoid excess (AME), characterized by severe hypertension and hypokalemic alkalosis. Cortisol is the offending mineralocorticoid in AME, as the result of a lack of 11beta-HSD2-mediated cortisol to cortisone inactivation. In this study, we describe mutations in the HSD11B2 gene in 3 additional AME kindreds in which probands presented in adult life, with milder phenotypes including the original seminal case reported by Stewart and Edwards. Genetic analysis of the HSD11B2 gene revealed that all probands were compound heterozygotes, for a total of 7 novel coding and noncoding mutations. Of the 7 mutations detected, 6 were investigated for their effects on gene expression and enzyme activity by the use of mutant cDNA and minigene constructs transfected into HEK 293 cells. Four missense mutations resulted in enzymes with varying degrees of activity, all <10% of wild type. A further 2 mutations generated incorrectly spliced mRNA and predicted severely truncated, inactive enzyme. The mothers of 2 probands heterozygous for missense mutations have presented with a phenotype indistinguishable from "essential" hypertension. These genetic and biochemical data emphasize the heterogeneous nature of AME and the effects that heterozygosity at the HSD11B2 locus can have on blood pressure in later life.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
7/12. Inflammatory myopathies in children.Juvenile idiopathic inflammatory myopathies are rare conditions that are probably autoimmune in nature. Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy. This article describes a recent patient who presented with typical JDM and uses her case to discuss aspects of the childhood inflammatory myopathies.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
8/12. Hypertrophic pyloric stenosis in twins: same genes or same environments?The aetiology of infantile hypertrophic pyloric stenosis (IHPS) remains obscure. Cases in twins, usually monozygotic, have been sporadically reported as evidence for the genetic origin of the disease. We present a case of IHPS in a pair of dizygotic male twins together with a review of the literature, focusing on the question of whether the twin cases actually support a genetic or an acquired nature of IHPS.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
9/12. Congenital plaque-type glomuvenous malformations presenting in childhood.BACKGROUND: Glomuvenous malformations (GVMs) are now considered a separate entity from venous malformations. The rarest type of GVM is the generalized congenital plaque-type GVM. OBSERVATIONS: We present 10 new cases of congenital plaque-type GVM and describe their clinical progression and treatment. Mutations in the glomulin gene were found in those patients who participated in the genetic study. CONCLUSIONS: Congenital plaque-type GVMs are unique in their congenital nature, extensive distribution, difficult to diagnose and treat, and progressive involvement after birth. Most cases are familial, yet affected relatives usually have only minor lesions. The lesions of congenital plaque-type GVM are severe, visible at birth, and usually mistaken for extensive venous malformations. vascular malformations are divided by hemodynamic type into slow-flow and fast-flow lesions. Slow-flow lesions are subcategorized as capillary, lymphatic, and venous.(1) Capillary malformations are flat, sharply demarcated, red-pink vascular stains of the skin commonly referred to as port-wine stains. These persist throughout life and are characterized histologically by dilated capillaries within the dermis. They slowly increase in size with age. Lymphatic malformations are spongelike collections of abnormal channels and spaces that contain clear lymphatic fluid, causing an excess of fluid to accumulate and dilate the lymphatic channels. This results in swelling of the affected area and, if extensive, can cause enlargement of soft tissues and bones.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
10/12. A clinical grading scale to predict malignant hyperthermia susceptibility.BACKGROUND: The diagnosis of an acute malignant hyperthermia reaction by clinical criteria can be difficult because of the nonspecific nature and variable incidence of many of the clinical signs and laboratory findings. Development of a standardized means for estimating the qualitative likelihood of malignant hyperthermia in a given patient without the use of specialized diagnostic testing would be useful for patient management and would promote research into improved means for diagnosing this disease. methods: Using the Delphi method and an international panel of 11 experts on malignant hyperthermia, a multifactor malignant hyperthermia clinical grading scale comprising standardized clinical diagnostic criteria was developed for classification of existing records and for application to new patients. RESULTS: This scale ranks the qualitative likelihood that an adverse anesthetic event represents malignant hyperthermia (malignant hyperthermia event rank) and that, with further investigation of family history, an individual patient will be diagnosed as malignant hyperthermia susceptible (malignant hyperthermia susceptibility rank). The assigned rank represents a lower bound on the likelihood of malignant hyperthermia. The clinical grading scale requires the anesthesiologist to judge whether specific clinical signs are appropriate for the patient's medical condition, anesthetic technique, and surgical procedure. CONCLUSIONS: The malignant hyperthermia clinical grading scale is recommended for use as an aid to the objective definition of this disease. It use may improve malignant hyperthermia research by allowing comparisons among well-defined groups of patients. This clinical grading system provides a new and comprehensive clinical case definition for the malignant hyperthermia syndrome.- - - - - - - - - - ranking = 1keywords = nature (Clic here for more details about this article) |
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