1/23. Char syndrome, an inherited disorder with patent ductus arteriosus, maps to chromosome 6p12-p21.BACKGROUND: Patent ductus arteriosus (PDA) is a relatively common form of congenital heart disease. Although polygenic inheritance has been implicated, no specific gene defects causing PDA have been identified to date. Thus, a positional cloning strategy was undertaken to determine the gene responsible for the Char syndrome, an autosomal dominant disorder characterized by PDA, facial dysmorphism, and hand anomalies. methods AND RESULTS: A genome scan was performed with 46 members of 2 unrelated families in which the disease was fully penetrant but the phenotype differed. Significant linkage was achieved with several polymorphic dna markers mapping to chromosome 6p12-p21 (maximal 2-point lod score of 8.39 with D6S1638 at theta=0.00). Haplotype analysis identified recombinant events that defined the Char syndrome locus with high probability to a 3. 1-cM region between D6S459/D6S1632/D6S1541 and D6S1024. CONCLUSIONS: A familial syndrome in which PDA is a common feature was mapped to a narrow region of chromosome 6p12-p21. Additional analysis with other families and polymorphic markers as well as evaluation of potential candidate genes should lead to the identification of the Char syndrome gene, which will provide insights into cardiogenesis as well as limb and craniofacial development.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
2/23. Early prenatal diagnosis of the ICF syndrome.The ICF syndrome (immunodeficiency, (para)centromeric instability and facial abnormalities) is a rare autosomal recessive disorder with characteristic cytogenetic aberrations of chromosomes 1, 9 and 16 in lymphocytes. Previously, only one case has been diagnosed prenatally in the second trimester of pregnancy by fetal blood sampling. We report the first early prenatal exclusion of the ICF syndrome by chorionic villous sampling (CVS) and linkage analysis in a family with a previous affected child. The fetus was heterozygous for marker D20S850 closely linked to the ICF locus. The family was counselled of a probability of over 90% that the fetus would be unaffected. Postnatal chromosome analysis on peripheral blood was normal and thus confirmed the prenatal diagnosis.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
3/23. Localization of clinical syndromes using DWI: two examples of the "capsular" warning syndrome.The capsular warning syndrome (CWS) is a subtype of transient ischemic attack characterized by its recurrent nature, absence of cortical signs, and high probability of early capsular stroke. Currently, standard imaging techniques have identified only internal capsule lesions in this entity. The authors present 2 cases with an otherwise typical CWS in whom a brainstem stroke was detected by diffusion-weighted imaging (DWI). DWI's ability to differentiate between acute and chronic infarcts may assist in more accurate localization of clinical syndromes.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
4/23. Shwachman-diamond syndrome in a Mexican family.Shwachman-diamond Syndrome (SDS) is an inherited condition with multisystemic abnormalities including pancreatic exocrine dysfunction, neutropenia, short stature, and skeletal abnormalities. In this report, we describe the case of a 14-year-old female with a history of neutropenia, pancreatic exocrine insufficiency and pancreatic endocrine sufficiency, pancreatic lipomatosis (10), and the development of myeloid leukemia. Postmortem examination revealed a high probability of SDS. We also describe the clinical findings in the patient's six siblings, suggesting this as a familial form of SDS. Because the gene(s) responsible for this syndrome have not yet been identified, genetic confirmation is not yet possible. This is the first report in the literature of a Mexican family with probable SDS.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
5/23. Pallister-Killian syndrome: difficulties of prenatal diagnosis.The first prenatal diagnosis of Pallister-Killian syndrome (PKS) was reported by Gilgenkrantz et al. in1985. Since this report, about 60 prenatal cases have been reported but both sonographic and cytogenetic diagnoses remain difficult. Although ultrasound anomalies such as congenital diaphragmatic hernia, polyhydramnios and rhizomelic micromelia in association with fetal overgrowth are very suggestive of the syndrome, they are inconstant and they may even be absent. The mosaic distribution of the supernumerary isochromosome 12p greatly increases these difficulties. No prenatal cytogenetic technique is sensitive enough to ensure prenatal diagnosis and false-negative results have been described on fetal blood, chorionic villi and amniocentesis. We report here two prenatal cases of PKS which illustrate the great variability of the fetal phenotype. In reviewing the 63 reported cases, we attempt to determine ultrasound indicators of the syndrome and to define a cytogenetic strategy. In cases where ultrasound indicators are present, our proposal is first to perform chorionic villus or placental sampling and then amniocentesis when the first cytogenetic result is normal. fetal blood sampling is the least indicated method because of the low frequency of the isochromosome in lymphocytes. In this cytogenetic strategy, fluorescent in situ hybridization (FISH) and especially interphase FISH on non-cultured cells increases the probability or identifying the isochromosome. A misdiagnosis remains possible when ultrasound is not contributory; the identification of new discriminating ultrasound indicators would be very helpful in this context.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
6/23. Three cases of tetrasomy 9p.We report three cases of tetrasomy 9p, two of which were confirmed prenatally. All three had characteristic findings on ultrasound and at birth. We also present a review of the literature, which suggests that a recognizable phenotype for this condition is emerging. Common findings on prenatal ultrasound include intrauterine growth restriction, ventriculomegaly, cleft lip or palate, and renal anomalies. These findings can provide a clue toward the prenatal diagnosis of this condition. There is also a clearly recognizable phenotype at birth. Facial characteristics include hypertelorism, broad nasal bridge/bulbous or beaked nose, cleft lip/palate, ear anomalies, and micrognathia. The exact extent of the isochromosome does not seem to predict severity, but mosaic cases are less severe, or at least have a greater probability of survival.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
7/23. Sezary's syndrome: a cytogenetic, cytophotometric and autoradiographic study.Cytophotometric, cytogenetic, and autoradiographic studies were performed in cells of three patients suffering from clinically diagnosed Sezary's syndrome with erythroderma and the presence of abnormal lymphoid cells in the peripheral blood, skin, bone marrow and lymph-nodes. Feulgen dna cytophotometry of cells in the peripheral blood and skin lesions showed marked aneuploidy and tetraploidy. Multiple translocations were identified with a G-banding technique. The chromosomal abnormalities varied widely between the patients, but C and D group chromosomes were more frequently involved than others. All breakpoints of the translocations were localised in the centromeric region. autoradiography of blood and skin samples revealed many labelled cells in the skin and a lower number in the blood, indicating cell proliferation in the skin. It is concluded that the pathological cells occurring in the sezary syndrome are abnormal lymphoid cells with a tendency to proliferate in the dermis. The variability observed between and in the patients is in all probability due to a difference in the degree of dedifferentiation.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
8/23. Clinical features associated with lesions other than pituitary adenoma in patients with an optic chiasmal syndrome.PURPOSE: Pituitary adenomas are the most common cause of an optic chiasmal syndrome, and treatment of these lesions is considerably different from the treatment of most of the other lesions in this region. Although the diagnosis of a pituitary adenoma is usually inferred from the results of neuroimaging, lesions other than pituitary adenomas can have an appearance that suggests an adenoma. The objective of our study was to determine whether there are clinical findings that suggest a lesion producing a chiasmal syndrome is something other than a pituitary adenoma. DESIGN: Retrospective, case-controlled, analysis of medical record data. methods: The records of the Neuro-ophthalmology Unit of the Wilmer eye Institute were searched for patients with a chiasmal syndrome who had been evaluated before treatment and for whom pathologic or laboratory confirmation of the etiology was available. Presenting clinical features of these patients were recorded, and analyses with both a single variable and multiple variables were performed to determine whether there were any features that could identify with a high degree of probability the etiology of the lesion producing the syndrome. RESULTS: The search revealed 149 patients who met the inclusion criteria, including 90 patients with pituitary adenomas and 59 patients with other lesions. Variables that were highly suggestive of an etiology other than pituitary adenoma included symptomatic visual loss, younger age, unilateral optic disk pallor, a relative afferent pupillary defect, and an absolute or a complete visual field defect or one was greater inferiorly than superiorly. CONCLUSION: Although no single clinical feature can be used to determine the specific nature of a lesion that produces an optic chiasmal syndrome, certain features are highly suggestive of an etiology other than pituitary adenoma. When these features are present, the likelihood that a suprasellar lesion is a pituitary adenoma is much lower, regardless of the appearance on neuroimaging.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
9/23. Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective.The interaction of insulin with its cell surface receptor is the first step in insulin action and the first identified target of insulin resistance. The insulin resistance in several syndromic forms of extreme insulin resistance has been shown to be caused by mutations in the receptor gene. We studied 8 female patients with the type A form of extreme insulin resistance and 3 patients (2 male and 1 female) with the Rabson-Mendenhall syndrome and followed the natural history of these patients for up to 30 years. The 11 patients ranged in age from 7 to 32 years at presentation. All 11 patients had extreme insulin resistance, acanthosis nigricans, and hyperandrogenism in the female patients, and all but 1 were of normal body weight. This phenotype strongly predicts mutations in the insulin receptor: of the 8 patients studied, 7 were found to have mutations. Similar results from the literature are found in other patients with type A and Rabson-Mendenhall syndromes and leprechaunism. The hyperandrogenic state resulting from hyperinsulinemia and insulin resistance in these patients was extreme: 6 of 8 patients had ovarian surgery to correct the polycystic ovarian syndrome and elevation of serum testosterone. By contrast, a larger group of insulin-resistant patients who were obese with hyperandrogenism, insulin resistance, and acanthosis nigricans (hair-AN syndrome) did not have a high probability of mutations in the insulin receptor. The morbidity and mortality of these patients were high: 3 of 11 died, 9 of 11 were diabetic and 1 had impaired glucose tolerance, and 7 of 9 patients had 1 or more severe complication of diabetes. Our literature review revealed that the mortality of leprechaunism is so high that the term leprechaunism should be restricted to infants or young children under 2 years of age. Analogous to patients with the common forms of type 2 diabetes, these patients had a heterogeneous course. In 2 patients who were able to maintain extremely high endogenous insulin production, the fasting blood glucose remained normal even though post-glucose-challenge levels were elevated. Most patients, however, required large doses of exogenous insulin to ameliorate the severe hyperglycemia. Preliminary results of a recent study suggest that recombinant leptin administration may benefit these patients with severe insulin resistance.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
10/23. Short-lasting unilateral neuralgiform headache attacks with tearing and conjunctival injection: the first "symptomatic" case?A 36-year-old man was suffering from brief, unilateral and short-lasting pain attacks always associated with marked homolateral tearing and conjunctival injection, both presenting in a cluster fashion. An arteriovenous malformation was subsequently discovered in the homolateral cerebellopontine angle. The clinical picture shares similarities with both cluster headache and trigeminal neuralgia, although it can not be accurately placed with either of these forms. patients with similar symptoms have previously been described in detail, and on the basis of these few descriptions a new syndrome "short-lasting" unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating, and rhinorrhoea has been postulated. Assuming the validity of this syndrome as an entity, this case is in all probability its first "symptomatic" example. Careful evaluation of the varieties of cluster headache and trigeminal neuralgia, and the reporting of similar new cases as they arise are necessary to establish the nosologic boundaries of this syndrome.- - - - - - - - - - ranking = 1keywords = probability (Clic here for more details about this article) |
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