Angioedema

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Luisa María Holguín-Gómez

2016-10-01

Full Text Available Angioedema is defined as edema of the skin or mucosa, including the respiratory and the gastrointestinal mucosa, which is self-limiting, and in most cases is completely resolved in less than 72 hours. It occurs due to increased permeability of the mucosal and submucosal capillaries and postcapillary venules, with resulting plasma extravasation. There are different types of angioedema: histaminergic (which may be mediated by immunoglobulin E, hereditary, from acquired C1 inhibitor deficiency, from angiotensin converting enzyme inhibitor, bradykinin-mediated, and non-histaminergic idiopathic angioedema. Treatment depends on the cause of angioedema, age, and the frequency and severity of manifestations. The main measures are avoiding external triggers or causes, giving antihistamines, steroids, or adrenaline for histaminergic angioedema; replacing the deficient protein or blocking the action of bradykinin in C1 inhibitor deficiency and angioedema from angiotensin converting enzyme inhibitor.

Hereditary angioedema in women

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Bouillet Laurence

2010-07-01

Full Text Available Abstract Women with hereditary angioedema (HAE are more likely to be symptomatic that men. Hormonal factors (puberty, contraception, pregnancy,.... play a significant role in the precipitation or worsening of the condition in women. So, combined contraceptive pills are not indicated and progestogen pill must be preferred. During pregnancy, attack rate can increase (38-48% of women. C1Inhibitor concentrate and tranexamic acid can be used during pregnancy. Attenuated androgens for long term prophylaxis are effective but side effects appear more often in female patients. These side effects are dose dependant and can be attenuated by titrating the dose down the lowest effective level.

Management of upper airway edema caused by hereditary angioedema

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Farkas Henriette

2010-07-01

Full Text Available Abstract Hereditary angioedema is a rare disorder with a genetic background involving mutations in the genes encoding C1-INH and of factor XII. Its etiology is unknown in a proportion of cases. Recurrent edema formation may involve the subcutis and the submucosa - the latter can produce obstruction in the upper airways and thereby lead to life-threatening asphyxia. This is the reason for the high, 30-to 50-per-cent mortality of undiagnosed or improperly managed cases. Airway obstruction can be prevented through early diagnosis, meaningful patient information, timely recognition of initial symptoms, state-of-the-art emergency therapy, and close monitoring of the patient. Prophylaxis can substantially mitigate the risk of upper airway edema and also improve the patients' quality of life. Notwithstanding the foregoing, any form of upper airway edema should be regarded as a potentially life-threatening condition. None of the currently available prophylactic modalities is capable of preventing UAE with absolute certainty.

Hereditary angioedema: a bradykinin-mediated swelling disorder.

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Björkqvist, Jenny; Sala-Cunill, Anna; Renné, Thomas

2013-03-01

Edema is tissue swelling and is a common symptom in a variety of diseases. Edema form due to accumulation of fluids, either through reduced drainage or increased vascular permeability. There are multiple vascular signalling pathways that regulate vessel permeability. An important mediator that increases vascular leak is the peptide hormone bradykinin, which is the principal agent in the swelling disorder hereditary angioedema. The disease is autosomal dominant inherited and presents clinically with recurrent episodes of acute swelling that can be life-threatening involving the skin, the oropharyngeal, laryngeal, and gastrointestinal mucosa. Three different types of hereditary angiodema exist in patients. The review summarises current knowledge on the pathophysiology of hereditary angiodema and focuses on recent experimental and pharmacological findings that have led to a better understanding and new treatments for the disease.

Overview of hereditary angioedema caused by C1-inhibitor deficiency: assessment and clinical management.

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Bork, K; Davis-Lorton, M

2013-02-01

Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a rare, autosomal-dominant disease. HAE-C1-INH is characterized by recurrent attacks of marked, diffuse, nonpitting and nonpruritic skin swellings, painful abdominal attacks, and laryngeal edema. The extremities and the gastrointestinal tract are most commonly affected. Swelling of the upper respiratory mucosa poses the greatest risk because death from asphyxiation can result from laryngealedema. HAE-C1-INH attacks are variable, unpredictable, and may be induced by a variety of stimuli, including stress or physical trauma. Because the clinical presentation of HAE-C1-INH is similar to other types of angioedema, the condition may be a challenge to diagnose. Accurate identification of HAE-C1-INH is critical in order to avoid asphyxiation by laryngeal edema and to improve the burden of disease. Based on an understanding of the underlying pathophysiology of IHAE-C1-INH, drugs targeted specifically to the disease, such as C1-inhibitor therapy, bradykinin B2-receptor antagonists, and kallikrein-inhibitors, have become available for both treatment and prevention of angioedema attacks. This article reviews the clinical features, differential diagnosis, and current approaches to management of HAE-C1-INH.

Gastrointestinal manifestations of hereditary angioedema diagnosed by ultrasound in the emergency department.

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Riguzzi, Christine; Losonczy, Lia; Teismann, Nathan; Herring, Andrew A; Nagdev, Arun

2014-11-01

Abdominal angioedema is a less recognized type of angioedema, which can occur in patients with hereditary angioedema (HAE). The clinical signs may range from subtle, diffuse abdominal pain and nausea, to overt peritonitis. We describe two cases of abdominal angioedema in patients with known HAE that were diagnosed in the emergency department by point-of-care (POC) ultrasound. In each case, the patient presented with isolated abdominal complaints and no signs of oropharyngeal edema. Findings on POC ultrasound included intraperitoneal free fluid and bowel wall edema. Both patients recovered uneventfully after receiving treatment. Because it can be performed rapidly, requires no ionizing radiation, and can rule out alternative diagnoses, POC ultrasound holds promise as a valuable tool in the evaluation and management of patients with HAE.

The establishment and utility of Sweha-Reg: a Swedish population-based registry to understand hereditary angioedema

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Werner Sonja

2007-11-01

Full Text Available Abstract Background The importance of acquiring comprehensive epidemiological and clinical data on hereditary angioedema has increasingly caught the attention of physicians and scientists around the world. The development of networks and creation of comprehensive policies to improve care of people suffering from rare diseases, such as hereditary angioedema, is a stated top priority of the European Union. Hereditary angioedema is a rare disease, that it may be life-threatening. Although the exact prevalence is unknown, current estimates suggest that it is 1/10,000–1/150,000 individuals. The low prevalence requires combined efforts to gain accurate epidemiological data on the disease and so give us tools to reduce morbidity and mortality, and improve quality of life of sufferers. Methods Sweha-Reg is a population-based registry of hereditary angioedema in Sweden with the objectives of providing epidemiological data, and so creates a framework for the study of this disease. The registry contains individual-based data on diagnoses, treatments and outcomes. Conclusion The present manuscript seeks to raise awareness of the existence of Sweha-Reg to stimulate the international collaboration of registries. A synthesis of data from similar registries across several countries is required to approach an inclusive course understanding of HAE.

Hereditary Angioedema - Consequences of a New Treatment Paradigm in Denmark

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Bygum, Anette

2014-01-01

stopped long-term prophylaxis with danazol or tranexamic acid and changed treatment regimen to on-demand treatment with C1 inhibitor concentrate or icatibant. At least 10% of the attacks remained un-treated. More than half of the patients felt that hereditary angioedema had a significant psychological...

Prophylactic Therapy for Hereditary Angioedema.

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Longhurst, Hilary; Zinser, Emily

2017-08-01

Long-term prophylaxis is needed in many patients with hereditary angioedema and poses many challenges. Attenuated androgens are effective in many but are limited by side effect profiles. There is less evidence for efficacy of tranexamic acid and progestagens; however, the small side effect profile makes tranexamic acid an option for prophylaxis in children and progestagens an option for women. C1 inhibitor is beneficial, but at present requires intravenous delivery and may need dose titration for maximum efficacy. Short-term prophylaxis should be considered for all procedures. New therapies are promising in overcoming many problems encountered with current options for long-term prophylaxis. Copyright © 2017 Elsevier Inc. All rights reserved.

Gastrointestinal Manifestations of Hereditary Angioedema Diagnosed by Ultrasound in the Emergency Department

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Christine Riguzzi

2014-11-01

Full Text Available Abdominal angioedema is a less recognized type of angioedema, which can occur in patients with hereditary angioedema (HAE. The clinical signs may range from subtle, diffuse abdominal pain and nausea, to overt peritonitis. We describe two cases of abdominal angioedema in patients with known HAE that were diagnosed in the emergency department by point-of-care (POC ultrasound. In each case, the patient presented with isolated abdominal complaints and no signs of oropharyngeal edema. Findings on POC ultrasound included intraperitoneal free fluid and bowel wall edema. Both patients recovered uneventfully after receiving treatment. Because it can be performed rapidly, requires no ionizing radiation,and can rule out alternative diagnoses, POC ultrasound holds promise as a valuable tool in the evaluation and management of patients with HAE. [West J Emerg Med. 2014;15(7:-0.

Successful treatment of hereditary angioedema with bradykinin B2-receptor antagonist icatibant.

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Krause, Karoline; Metz, Martin; Zuberbier, Torsten; Maurer, Marcus; Magerl, Markus

2010-04-01

The bradykinin B2 receptor antagonist icatibant has recently become available for treating hereditary angioedema. Our observations demonstrate icatibant to be effective and safe for the treatment of both, abdominal and cutaneous attacks in a practice setting beyond clinical studies.

Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema

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Aygören-Pürsün E

2016-09-01

Full Text Available Emel Aygören-Pürsün,1 Anette Bygum,2 Kathleen Beusterien,3 Emily Hautamaki,4 Zlatko Sisic,5 Henrik B Boysen,6 Teresa Caballero7 1Angioedema Centre, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt, Germany; 2Hereditary Angioedema Centre Denmark, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark; 3Outcomes Research Strategies in Health, Washington, DC, 4Patient Reported Outcomes, Oxford Outcomes Inc., an ICON plc company, Bethesda, MD, USA; 5ViroPharma Incorporated, Chatsworth House, Maidenhead, UK; 6HAEi – Hereditary Angioedema International Patient Organization for C1 Inhibitor Deficiencies, Skanderborg, Denmark; 7Allergy Department, Hospital La Paz Institute for Health Research (IdiPaz, Biomedical Research Network on Rare Diseases U754 (CIBERER, University Hospital La Paz, Madrid, Spain Objective: To estimate health status utility (preference weights for hereditary angioedema (HAE during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe survey. Utility measures quantitatively describe the net impact of a condition on a patient’s life; a score of 0.0 reflects death and 1.0 reflects full health.Study design and methods: The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks.Results: Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation

Open-label, multicenter study of self-administered icatibant for attacks of hereditary angioedema

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Aberer, W; Maurer, M; Reshef, A

2014-01-01

Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self-administered ica...

Hereditary Angioedema: The Economics of Treatment of an Orphan Disease.

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Lumry, William Raymond

2018-01-01

This review will discuss the cost burden of hereditary angioedema on patients, healthcare systems, and society. The impact of availability of and access to novel and specific therapies on morbidity, mortality, and the overall burden of disease will be explored along with potential changes in treatment paradigms to improve effectiveness and reduce cost of treatment. The prevalence of orphan diseases, legislative incentives to encourage development of orphan disease therapies and the impact of orphan disease treatment on healthcare payment systems will be discussed.

The burden of illness in patients with hereditary angioedema.

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Banerji, Aleena

2013-11-01

Hereditary angioedema (HAE) is a rare genetic disease characterized by long-term recurrent attacks of subcutaneous or submucosal edema in different parts of the body. A comprehensive review of the literature on burden of illness for patients with HAE is presented. A Boolean search was performed using MEDLINE and EMBASE databases and the Internet. Articles discussing aspects of the burden of illness in HAE were selected. Topics focused on the course of the disease, nature of attacks, treatment, quality of life, and costs. Hereditary angioedema is associated with a significant and multifaceted disease burden. Diagnosis is often delayed for years, with patients receiving ineffective treatment and unnecessary medical procedures before diagnosis. HAE attacks are painful, unpredictable, and debilitating and often require emergency medical attention. Attacks can affect a patient's daily activities, including work or schooling. Depression and anxiety are prevalent in patients with HAE. Recent advances in treatment provide patients with effective and well-tolerated prophylactic and on-demand therapeutic options. However, end points specific to HAE that better measure the impact of treatment on disease burden are lacking. Furthermore, there is a notable paucity of literature directed toward physicians who are instrumental in diagnosing and treating patients with HAE (eg, emergency department). More publications are broadening the understanding of HAE. However, important gaps remain. Effective management of HAE requires a more comprehensive understanding of the disease burden so that disease management can be individualized to meet specific patient needs. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Hereditary angioedema: what the gastroenterologist needs to know

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Ali MA

2014-11-01

Full Text Available M Aamir Ali, Marie L Borum Division of Gastroenterology and Liver Diseases, George Washington University, Washington, DC, USA Abstract: Up to 93% of patients with hereditary angioedema (HAE experience recurrent abdominal pain. Many of these patients, who often present to emergency departments, primary care physicians, general surgeons, or gastroenterologists, are misdiagnosed for years and undergo unnecessary testing and surgical procedures. Making the diagnosis of HAE can be challenging because symptoms and attack locations are often inconsistent from one episode to the next. Abdominal attacks are common and can occur without other attack locations. An early, accurate diagnosis is central to managing HAE. Unexplained abdominal pain, particularly when accompanied by swelling of the face and extremities, suggests the diagnosis of HAE. A family history and radiologic imaging demonstrating edematous bowel also support an HAE diagnosis. Once HAE is suspected, C4 and C1 esterase inhibitor (C1-INH laboratory studies are usually diagnostic. Patients with HAE may benefit from recently approved specific treatments, including plasma-derived C1-INH or recombinant C1-INH, a bradykinin B2-receptor antagonist, or a kallikrein inhibitor as first-line therapy and solvent/detergent-treated or fresh frozen plasma as second-line therapy for acute episodes. Short-term or long-term prophylaxis with nanofiltered C1-INH or attenuated androgens will prevent or reduce the frequency and severity of episodes. Gastroenterologists can play a critical role in identifying and treating patients with HAE, and should have a high index of suspicion when encountering patients with recurrent, unexplained bouts of abdominal pain. Given the high rate of abdominal attacks in HAE, it is important for gastroenterologists to appropriately diagnose and promptly recognize and treat HAE, or refer patients with HAE to an allergist. Keywords: hereditary angioedema, abdominal pain, diagnosis

Classification, diagnosis, and approach to treatment for angioedema

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Cicardi, M; Aberer, W; Banerji, A

2014-01-01

Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have...... angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired...... and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema....

Effectiveness of icatibant for treatment of hereditary angioedema attacks is not affected by body weight

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Caballero, Teresa; Zanichelli, Andrea; Aberer, Werner

2018-01-01

Background: Icatibant is a bradykinin B2-receptor antagonist used for the treatment of hereditary angioedema attacks resulting from C1-inhibitor deficiency. Treatment is not adjusted by body weight however the impact of body mass index (BMI) on the effectiveness of icatibant is not documented in ...

Breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis are responsive to icatibant

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Aberer, Werner; Maurer, Marcus; Bouillet, Laurence

2017-01-01

BACKGROUND: Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic treatments can be prescribed to prevent attacks. However, despite the use of long-term prop...

Optimum Use of Acute Treatments for Hereditary Angioedema: Evidence-Based Expert Consensus

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Hilary Longhurst

2018-01-01

Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients’ quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze), a recombinant C1 inhibitor (Ruconest/Conestat alpha), a kallikrein inhibitor (Ecallantide), and a bradykinin B2 receptor inhibitor (Icatibant) are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophyla...

Socioeconomic burden of hereditary angioedema: results from the hereditary angioedema burden of illness study in Europe.

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Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Wait, Suzanne; Boysen, Henrik B; Caballero, Teresa

2014-07-04

Hereditary angioedema (HAE) due to C1 inhibitor deficiency is a rare but serious and potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The study objective was to characterize direct and indirect resource utilization associated with HAE from the patient perspective in Europe. The study was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE via a cross-sectional survey of HAE patients, including direct and indirect resource utilization during and between attacks for patients and their caregivers over the past 6 months. A regression model examined predictors of medical resource utilization. Overall, 164 patients had an attack in the past 6 months and were included in the analysis. The most significant predictor of medical resource utilization was the severity of the last attack (OR 2.6; p career/educational advancement. HAE poses a considerable burden on patients and their families in terms of direct medical costs and indirect costs related to lost productivity. This burden is substantial at the time of attacks and in between attacks.

Comparing acquired angioedema with hereditary angioedema (types I/II): findings from the Icatibant Outcome Survey.

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Longhurst, H J; Zanichelli, A; Caballero, T; Bouillet, L; Aberer, W; Maurer, M; Fain, O; Fabien, V; Andresen, I

2017-04-01

Icatibant is used to treat acute hereditary angioedema with C1 inhibitor deficiency types I/II (C1-INH-HAE types I/II) and has shown promise in angioedema due to acquired C1 inhibitor deficiency (C1-INH-AAE). Data from the Icatibant Outcome Survey (IOS) were analysed to evaluate the effectiveness of icatibant in the treatment of patients with C1-INH-AAE and compare disease characteristics with those with C1-INH-HAE types I/II. Key medical history (including prior occurrence of attacks) was recorded upon IOS enrolment. Thereafter, data were recorded retrospectively at approximately 6-month intervals during patient follow-up visits. In the icatibant-treated population, 16 patients with C1-INH-AAE had 287 attacks and 415 patients with C1-INH-HAE types I/II had 2245 attacks. Patients with C1-INH-AAE versus C1-INH-HAE types I/II were more often male (69 versus 42%; P = 0·035) and had a significantly later mean (95% confidence interval) age of symptom onset [57·9 (51·33-64·53) versus 14·0 (12·70-15·26) years]. Time from symptom onset to diagnosis was significantly shorter in patients with C1-INH-AAE versus C1-INH-HAE types I/II (mean 12·3 months versus 118·1 months; P = 0·006). Patients with C1-INH-AAE showed a trend for higher occurrence of attacks involving the face (35 versus 21% of attacks; P = 0·064). Overall, angioedema attacks were more severe in patients with C1-INH-HAE types I/II versus C1-INH-AAE (61 versus 40% of attacks were classified as severe to very severe; P types I/II, respectively. © 2016 British Society for Immunology.

The hereditary angioedema burden of illness study in Europe (HAE-BOIS- Europe)

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Bygum, Anette; Aygören-Pürsün, Emel; Caballero, Teresa

2012-01-01

ABSTRACT: BACKGROUND: Hereditary angioedema (HAE) is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation...... of HAE-I or HAE-II. Data collection includes: (i) a survey on individuals' health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale); and (ii) one-on-one interviews to collect...

Hereditary angioedema with C1 inhibitor deficiency: delay in diagnosis in Europe.

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Zanichelli, Andrea; Magerl, Markus; Longhurst, Hilary; Fabien, Vincent; Maurer, Marcus

2013-08-12

Hereditary angioedema (HAE) is a rare, debilitating, and potentially life-threatening disease characterized by recurrent edema attacks. Important advances in HAE treatment have been made, including the development of new therapies for treating or preventing attacks. Nevertheless, the disease is still frequently misdiagnosed and inappropriately treated, potentially exposing patients with laryngeal attacks to the risk of asphyxiation. The Icatibant Outcome Survey (IOS) is an international, observational study that documents the clinical outcome of HAE patients eligible for treatment with icatibant. Patient ages at first symptoms and at diagnosis were recorded at enrolment, and the delay between first symptoms and diagnosis was calculated. The median [range] diagnostic delay in HAE type I and II patients across eight countries was 8.5 years [0-62.0]. The median delay in diagnosis was longer for HAE type II versus type I (21 versus 8 years, respectively), although this did not quite reach statistical significance. Although it can be difficult to differentiate HAE symptoms from those of more common angioedema sub-types (e.g. idiopathic or acquired angioedema), our results show that HAE type I and II patients have an unacceptable delay in diagnosis, even those with a family history of the disease. Raising physician awareness of this disabling and potentially fatal disease may lead to a more accurate diagnosis and timely treatment.

Depressed activation of the lectin pathway of complement in hereditary angioedema

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Varga, L; Széplaki, G; Laki, J

2008-01-01

) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured...... by standard laboratory methods. MBL-2 genotypes were determined by polymerase chain reaction. Besides the complement alterations (low CP and C1INH activity, low C4-, C1INH concentrations), which characterize HAE, the level of MASP-2 was also lower (P = 0.0001) in patients compared with controls. Depressed LP...

Safety of C1-Esterase Inhibitor in Acute and Prophylactic Therapy of Hereditary Angioedema

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Busse, Paula; Bygum, Anette; Edelman, Jonathan

2014-01-01

BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products......, typically with off-label use or at supratherapeutic doses. OBJECTIVES: Active surveillance of safety and clinical usage patterns of pasteurized C1-inhibitor concentrate and the more recent pasteurized, nanofiltered C1-INH, with a particular interest in thromboembolic events. METHODS: A registry...

Angioedema hereditário: considerações sobre terapia Therapeutic approach of hereditary angioedema

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Kélem de Nardi Chagas

2004-09-01

HAE ser causado pelo mesmo defeito e acometer membros da mesma família, diferentes critérios têm sido estabelecidos para o tratamento desses pacientes. Foram indicados diferentes esquemas terapêuticos para HAE e alguns dos pacientes puderam ser seguidos sem terapia medicamentosa.PURPOSE: Hereditary Angioedema was first described by William Osler in 1888 and it is caused by a hereditary or acquired deficiency of C1 esterase inhibitor (C1-INH. Treatment is indicated for acute attacks or prophylaxis of angioedema which occur in the subcutaneous tissue respiratory or gastrointestinal tracts. Treatment includes attenuated androgens, inhibitors of kininogen or plasminogen, like tranexamic acid or e-aminocaproic acid and the administration of C1-INH concentrate. We describe the peculiarities of the treatment chosen for 10 patients (4 families with HAE and their evolution. METHODS: Ten patients (1-38 years old with HAE were diagnosed by clinical history and laboratory evaluation. The following tests were performed for the complement system: C1-INH, C4 and C3 levels and hemolytic assay (CH50 and APH50 for the classic and alternative pathways. Treatment was initiated considering severity of symptoms, age, gender and therapeutic response of the patient. RESULTS: Clinical evaluation showed: 4/10 patients with recurrent subcutaneous edema; 3/10 with previous laryngeal edema and 3/10 with sporadic symptoms. Different severity of symptoms was verified in the same family. The laboratory evaluation detected: low C1-INH levels (10/10; low serum C4 level (8/10; undetectable CH50 (3/10 and low CH50 levels (6/10; low APH50 levels (2/10. Six out of ten patients did not receive any specific treatment and 2 of them had high risk of asphyxia. One adolescent had been controlled with e-aminocaproic acid, one child had been changed from danazol to tranexamic acid, a 30 year old female patient had received oxandrolone and a 38 year old man had been treated with danazol. CONCLUSIONS: Although

Development of a disease-specific quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-QoL): Spanish multi-centre research project.

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Prior, Nieves; Remor, Eduardo; Gómez-Traseira, Carmen; López-Serrano, Concepción; Cabañas, Rosario; Contreras, Javier; Campos, Ángel; Cardona, Victoria; Cimbollek, Stefan; González-Quevedo, Teresa; Guilarte, Mar; de Rojas, Dolores Hernández Fernández; Marcos, Carmen; Rubio, María; Tejedor-Alonso, Miguel Ángel; Caballero, Teresa

2012-07-20

There is a need for a disease-specific instrument for assessing health-related quality of life in adults with hereditary angioedema due to C1 inhibitor deficiency, a rare, disabling and life-threatening disease. In this paper we report the protocol for the development and validation of a specific questionnaire, with details on the results of the process of item generation, domain selection, and the expert and patient rating phase. Semi-structured interviews were completed by 45 patients with hereditary angioedema and 8 experts from 8 regions in Spain. A qualitative content analysis of the responses was carried out. Issues raised by respondents were grouped into categories. Content analysis identified 240 different responses, which were grouped into 10 conceptual domains. Sixty- four items were generated. A total of 8 experts and 16 patients assessed the items for clarity, relevance to the disease, and correct dimension assignment. The preliminary version of the specific health-related quality of life questionnaire for hereditary angioedema (HAE-QoL v 1.1) contained 44 items grouped into 9 domains. To the best of our knowledge, this is the first multi-centre research project that aims to develop a specific health-related quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency. A preliminary version of the specific HAE-QoL questionnaire was obtained. The qualitative analysis of interviews together with the expert and patient rating phase helped to ensure content validity. A pilot study will be performed to assess the psychometric properties of the questionnaire and to decide on the final version.

Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group

NARCIS (Netherlands)

Cicardi, M.; Bork, K.; Caballero, T.; Craig, T.; Li, H. H.; Longhurst, H.; Reshef, A.; Zuraw, B.; Werner, Aberer; Aygören-Pürsün, Emel; Banerji, Aleena; Bjorkander, Janne; Boccon-Gibod, Isabelle; Konrad, Bork; Bouillet, Laurence; Bova, Maria; Bowen, Tom; Branco Ferreira, Manuel; Bygum, Anette; Caballero, Teresa; Cancian, Mauro; Castel-Branco, Maria Graça; Cicardi, Marco; Craig, Timothy; de Carolis, Caterina; Mihály, Enikö; Josè, Fabiani; Farkas, Henriette; Gompels, Mark; Gower, Richard; Groffik, Adriane; Grumach, Anete; Guillarte, Mar; Hernandez Landeros, Maria Esthela; Kaplan, Allen; Leibovich, Iris; Li, Henry; Lock, Bob; Longhurst, Hilary; Lumry, William; Malbran, Alejandro; Martinez-Saguer, Immaculada; Campos, Matta; Maurer, Marcus; Moldovan, Dumitru; Montinaro, Vincenzo; Nieto, Sandra; Nordenfelt, Patrik; Obtulovicz, Krystana; Zeerleder, Sacha

2012-01-01

Angioedema owing to hereditary deficiency of C1 inhibitor (HAE) is a rare, life-threatening, disabling disease. In the last 2 years, the results of well-designed and controlled trials with existing and new therapies for this condition have been published, and new treatments reached the market.

Psychometric Field Study of Hereditary Angioedema Quality of Life Questionnaire for Adults

DEFF Research Database (Denmark)

Prior, Nieves; Remor, Eduardo; Pérez-Fernández, Elia

2016-01-01

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) may affect health-related quality of life (HRQoL). A specific HRQoL questionnaire for adult patients with C1-INH-HAE, the HAE-QoL, has recently been developed in Spain. OBJECTIVE: The objective of this study...... was to perform a cross-cultural validation and psychometric study of the HAE-QoL in an international setting. METHODS: Cross-cultural adaptation of the Spanish HAE-QoL draft version and an international rating phase with experts were performed. The resultant version of the HAE-QoL, a clinical questionnaire...... with and without psychiatric and/or psychological care (median: 74 vs 103; P ≤ .001). CONCLUSIONS: The HAE-QoL, currently available in 18 languages, showed good reliability and validity evidence....

Caffeine as a cause of urticaria-angioedema

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Linda Tognetti

2014-01-01

Full Text Available We report the case of a young woman presenting with recurrent urticaria. The episodes occurred both in and out of the workplace. On three occasions it presented as urticaria-angioedema, requiring emergency care on one occassion. A thorough clinical history along with serological and allergological tests allowed a diagnosis of caffeine-induced urticaria-angioedema. We advised the patient to follow a caffeine-free diet and to avoid all caffeine or methylxanthine-containing drugs. After two years of caffeine abstinence, she had not experienced any further episodes of urticaria-angioedema. Only a few cases of caffeine-induced urticaria and/or anaphylaxis have been reported till date, with varying outcomes in allergologic investigations. Moreover, several cases are probably undiagnosed or misdiagnosed as idiopathic urticaria or as occupational allergy. We speculate that hypersensitivity to caffeine rather than autoimmine reaction may be the probable cause of urticaria. Caffeine should considered as a potential urticaria-inducing agent and should be included in the allergological test series.

Angioedema due to Systemic Isotretinoin Therapy

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Pelin Üstüner

2014-01-01

Full Text Available Angioedema is the swelling of the mucosal membranes as a variant of urticaria induced by hereditary C1 esterase inhibitor enzyme deficiency, certain foods, or drugs. Herein, we report the case of a 23-year-old woman, with mild-moderate acne presenting with widespread facial angioedema on the 2nd day of systemic isotretinoin treatment. The patient had taken no drugs other than isotretinoin in the preceding days and had no known food allergy. Her angioedema was resolved after the isotretinoin was discontinued. We want to draw the attention of dermatologists to this rare adverse allergic effect of isotretinoin which is frequently used in the treatment of acne vulgaris.

International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

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Farkas, H.; Martinez?Saguer, I.; Bork, K.; Bowen, T.; Craig, T.; Frank, M.; Germenis, A. E.; Grumach, A. S.; Luczay, A.; Varga, L.; Zanichelli, A.; Aberer, Werner; Andrejevic, Sladjana; Aygoeren?P?rs?n, Emel; Banerji, Alena

2016-01-01

BACKGROUND: The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1-INH-HAE.METHODS: During an expert panel meeting that took place during the 9th C1 Inhibitor Deficiency Workshop in Budapest, 2015 (www.haenet.hu), ped...

Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema.

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Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Boysen, Henrik B; Caballero, Teresa

2016-01-01

To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a condition on a patient's life; a score of 0.0 reflects death and 1.0 reflects full health. The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D) domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression) were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks. Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation of EQ-5D-based utilities. The mean utilities for an HAE attack and between attacks were 0.44 and 0.72, respectively. Utilities for an acute attack were dependent on the severity of pain of the last attack (0.61 for no pain or mild pain, 0.47 for moderate pain, and 0.08 for severe pain). There were no significant differences across countries. Mean utilities derived from the study approach compare sensibly with other disease states for both acute attacks and between attacks. The impacts of HAE translate into substantial health status disutilities associated with acute attacks as well as between attacks, documenting that the detrimental effects of HAE are meaningful from the patient perspective. Results were consistent across countries with regard to pain severity and in comparison to similar disease states. The results can be used to raise awareness of HAE as a serious disease with wide-ranging personal and social impacts.

Obstetrical Complications and Outcome in Two Families with Hereditary Angioedema due to Mutation in the F12 Gene

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Olivier Picone

2010-01-01

Full Text Available Backgroud. Hereditary angioedema (HAE is characterized by recurrent swelling of the skin, the abdomen (causing severe acute pain, and the airways. A recently discovered type caused by mutations in the factor XII gene (designated as HAE type III occurs mainly in women. Estrogens may play an important role, but few obstetrical complications have been reported. Case. We report the symptoms and obstetrical complications of women in two families with HAE attributable to the p. Thr328Lys mutation in the F12 gene. Clinical manifestations included acute and severe maternal abdominal pain, with transient ascites, laryngeal edema, and fetal and neonatal deaths. Patients had normal C4 levels and a normal C1 inhibitor gene. Administration of C1-inhibitor concentration twice monthly decreased the attack rate in one mother, and its predelivery administration (1000 U led to the delivery of healthy girls. Conclusions. Obstetricians and anesthesiologists should be aware of this rare cause of unexplained maternal ascites and in utero or fetal death associated with edema.

Hereditary angioedema type I: a case report

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Francisca Muñoz Peralta

2016-03-01

Full Text Available El angioedema hereditario es una enfermedad rara, de gran heterogeneidad en los síntomas, manifestándose con edema a nivel cutáneo, mucosa gastrointestinal y de laringe/faringe. Aunque existen tres variedades, el tipo I es el más frecuente y es provocado por una deficiencia en la síntesis del complemento C1 inhibidor. La gravedad de la clínica, junto a la baja prevalencia de la enfermedad y la necesidad de un tratamiento específico, hacen que el diagnóstico y tratamiento de dicha patología sea aún una asignatura pendiente para el médico de familia en atención primaria. Presentamos el caso de un adolescente varón con déficit de α-1 antitripsina desde los seis meses de edad, con aparición de angioedemas en piernas y brazos a los 11 años, diagnosticado de angioedema hereditario tipo I un año después. El diagnóstico definitivo de la enfermedad permitió instaurar un tratamiento adecuado a su patología, que consiste en la prevención de brotes que puedan comprometer la vida del paciente y, en el caso de que aparezcan, en la administración del complemento C1 inhibidor.

Refractory Angioedema in a Patient with Systemic Lupus Erythematosus

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Zahra Habibagahi

2015-07-01

Full Text Available Angioedema secondary to C1 inhibitor deficiency has been rarely reported to be associated with systemic lupus erythematosus. A genetic defect of C1 inhibitor produces hereditary angioedema, which is usually presented with cutaneous painless edema, but edema of the genital area, gastrointestinal and laryngeal tracts have also been reported. In lupus patients, angioedema may be the result of an acquired type of C1 inhibitor deficiency, most probably due to antibody formation directed against the C1 inhibitor molecule. Herein we report a new case of lupus nephritis that developed angioedema and a rapid course of disease progression with acute renal failure and alveolar hemorrhage without response to high dose steroid and plasmapheresis.

Health-related quality of life in relation to disease activity in adults with hereditary angioedema in Sweden.

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Nordenfelt, Patrik; Nilsson, Mats; Lindfors, Anders; Wahlgren, Carl-Fredrik; Björkander, Janne

2017-11-30

Health-related quality of life (HR-QoL) is impaired in patients with hereditary angioedema (HAE) but has not yet been satisfactorily described. To study HR-QoL in patients with HAE by combining different HR-QoL instruments with disease activity assessment. All adults in the Swedish HAE registry were invited to take part in this questionnaire study, which used the generic HR-QoL instruments, EuroQol 5 Dimensions 5 Level (EQ-5D-5L) and the RAND Corporation Short Form 36 (RAND-36), the disease-specific Angioedema Quality of Life instrument (AE-QoL), the recently introduced Angioedema Activity Score (AAS) form, and questionnaires on sick leave and prophylactic medication. Sixty-four of 133 adults (26 men, 38 women) between 18 and 91 years old responded. The most affected HR-QoL dimensions in the EQ-5D-5L were pain/discomfort and anxiety/depression; in the RAND-36, energy/fatigue, general health, pain; and, in the AE-QoL, fears/shame and fatigue/mood. Women had lower HR-QoL in the RAND-36 for general health and energy/fatigue (p 0 had significantly impaired HR-QoL. There were significant associations (p depression, and fatigue/mood are important aspects of HAE but the AE-QoL disregards pain. HR-QoL was not significantly affected by prophylaxis. Increased disease activity was associated with impaired HR-QoL, which justifies more active disease management.

In Vitro Fertilization Using Luteinizing Hormone-Releasing Hormone Injections Resulted in Healthy Triplets without Increased Attack Rates in a Hereditary Angioedema Case

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Ceyda Tunakan Dalgıç

2018-01-01

Full Text Available Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE is a rare, autosomal dominant disorder. The management of pregnant patients with C1-INH-HAE is a challenge for the physician. Intravenous plasma-derived nanofiltered C1-INH (pdC1INH is the only recommended option throughout pregnancy, postpartum, and breastfeeding period. In order to increase pregnancy rates, physicians use fertilization therapies increasing endogen levels of estrogens. Therefore, these techniques can provoke an increase in the number and severity of edema attacks in C1-INH-HAE. Our patient is a 32-year-old female, diagnosed with C1-INH-HAE type 1 since 2004. She had been taking danazol 50–200 mg/day for 9 years. Due to her pregnancy plans in 2013, danazol was discontinued. PdC1INH was prescribed regularly for prophylactic purpose. Triplet pregnancy occurred by in vitro fertilization using luteinizing hormone-releasing hormone (LHRH injections. In our patient, LHRH injections were done four times without causing any severe attack during in vitro fertilization. Angioedema did not worsen during pregnancy and delivery due to the prophylactic use of intravenous pdC1INH in our patient. According to the attack frequency and severity, there was no difference between the three pregnancy trimesters. To our knowledge, this is the first published case of C1-INH-HAE receiving in vitro fertilization therapies without any angioedema attacks during pregnancy and delivery and eventually having healthy triplets with the prophylactic use of intravenous pdC1INH.

Hereditary angioedema as a metabolic liver disorder: novel therapeutic options and prospects for cure

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Rohan Ameratuga

2016-11-01

Full Text Available Hereditary angioedema (HAE is a rare autosomal dominant disorder caused by mutations of the SERPING1 or the Factor 12 genes. It is potentially fatal, particularly if not identified at an early stage. Apart from androgens, which are contraindicated in children and in pregnant women, a range of effective, albeit very expensive treatments have recently become available for HAE patients. The cost of these new treatments is beyond the reach of most developing countries. At this time, there is no cure for the disorder. In spite of mutations of the SERPING1 gene, autoimmunity and infections are not prominent features of the condition. Here we present the argument that HAE should be viewed primarily as a metabolic liver disorder. This conceptual paradigm shift will stimulate basic research and may facilitate new therapeutic approaches to HAE outlined in this paper. We suggest several novel potential treatment options for HAE from the perspectives of clinical immunology, molecular biology and liver transplantation. Many of these offer the prospect of curing the disorder. The effectiveness of these options are rapidly improving in many cases and their risks are decreasing. Given the very high costs of treating HAE, some of these curative options may become feasible in the next decade.

Recent advances in management and treatment of hereditary angioedema.

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Sardana, Niti; Craig, Timothy J

2011-12-01

Hereditary angioedema (HAE) is a rare autosomal-dominant disease characterized by recurrent self-limiting episodes of skin and mucosal edema. Morbidity and mortality are significant, and new and pending therapies are now available to reduce the risk associated with the disease. To update the reader on new advances in HAE to improve patient care. We performed a literature search of Ovid, PubMed, and Google to develop this review. Articles that are necessary for the understanding and use of the new therapeutic options for HAE were chosen, and studies of high quality were used to support the use of therapies, and in most cases, results from phase III studies were used. Until recently, therapy for HAE attacks in the United States consisted of symptom relief with narcotics, hydration, and fresh-frozen plasma, which contains active C1 inhibitor. Therapy to prevent HAE attacks has been confined to androgens and, occasionally, antifibrinolytic agents; however, both drug groups have significant adverse effects. The approval of C1-inhibitor concentrate for prevention and acute therapy has improved efficacy and safety. Ecallantide has also been approved for therapy of attacks, and icatibant is expected to be approved in the next few months for attacks. Recombinant C1 inhibitor is presently in phase III studies and should be available for attacks in the near future. In this article we review the changing therapeutic options available for patients in 2011 and beyond.

Depression and anxiety in patients with hereditary angioedema.

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Fouche, Andrew S; Saunders, Erika F H; Craig, Timothy

2014-04-01

Hereditary angioedema (HAE) is characterized by edematous swelling attacks of the face, extremities, abdomen, genitalia, and upper airway. The potential for laryngeal swelling makes the disease life-threatening, and the swelling elsewhere contributes to the significant burden of illness. The increased risk for mental health disorders in HAE is due to the burden of disease and possibly associated activation of the immune system. To determine the prevalence of depression and anxiety in HAE patients and the most high-yield features of depression to target in a clinical encounter. Depression and anxiety symptoms were evaluated using the 29 items of the Hamilton Depression Rating Scale along with the 14-item Hamilton Anxiety Rating Scale. The sample size was 26 participants with a diagnosis of type 1 or 2 HAE drawn from a cohort of 60 adult patients. In addition, a literature search was performed regarding how immune modulation affects depression and anxiety. A total of 39% of participants were identified as experiencing depression of mild (50%), moderate (40%), or severe (10%) levels. Fifteen percent of participants displayed prominent anxiety, half of whom had mild anxiety, 25% moderate anxiety, and 25% severe anxiety. The literature on inflammation and depression suggests a possible link between HAE and depression. Our data and the literature support that depression and anxiety symptoms are common in patients with HAE and may be secondary to chronic disease burden, associated pathophysiologic features, or both. Treatment that addresses the psychosocial and mental health of HAE patients is critical for best practice. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The relationship between anxiety and quality of life in children with hereditary angioedema.

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Kessel, Aharon; Farkas, Henriette; Kivity, Shmuel; Veszeli, Nóra; Kőhalmi, Kinga V; Engel-Yeger, Batya

2017-11-01

The severe life-threatening characteristics of hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) can affect anxiety levels among pediatric patients. This emotional burden together with the physical restrictions of C1-INH-HAE may decrease children's health-related quality of life (HRQoL). (i) To compare anxiety state and trait between children with C1-INH-HAE and healthy controls; (ii) to examine the relationship between the level of anxiety of children with C1-INH-HAE, their disease activity/affected sites and their HRQoL; and (iii) to predict the HRQoL of children with C1-INH-HAE based on their anxiety level and disease activity/affected sites METHODS: Thirty-three children with C1-INH-HAE (aged 5-18 years) and 52 healthy controls were recruited from Israel and Hungary. All children completed the State-Trait Anxiety Inventory for Children (STAIC), the Pediatric Quality of Life Inventory (Peds-QL) demographic questionnaire and a disease activity and site questionnaire . Disease activity was defined as the number of attacks in last year. Both anxiety state and trait were significantly higher among children with C1-INH-HAE as compared to the controls (44.74±10.56 vs 38.76±10.67, Panxiety state (F 56,2 =4.69, P=.001) and trait (F 56,2 =9.06, Panxiety trait was correlated with the number of angioedema-affected sites (r=.52, P=.003). The presence of HAE attacks and higher anxiety trait predicted a lower HRQoL in children with C1-INH-HAE. C1-INH-HAE children have higher anxiety trait and state, which correlate with reduced HRQoL domains. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

[Acquired angioedema – clinical characteristic of the patients diagnosed in 2012-2016 with acquired C1 inhibitor deficiency].

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Stobiecki, Marcin; Czarnobilska, Ewa; Obtułowicz, Krystyna

Acquired angioedema is a rare disease caused by a deficiency of C1 esterase inhibitor with recurrent swelling symptoms. It may occur in the course of lymphoproliferative disorders or autoimmune diseases. Symptoms resemble hereditary angioedema, and the only differentiating features is negative family history, late onset of symptoms and accompanying lymphoproliferative disorder. The aim of the study was to analyze the cases of acquired angioedema. The retrospective analysis of 341 patients from the registry of patients with C1 inhibitor deficiency. Results: We identified 4 patients among 119 with HAE (3.57%) diagnosed in this same period of time 2012-2016 who fulfilled the criteria of acquired edema. In two cases the primary reason of angioedema was lymphoproliferive disease, in two monoclonal gammapathy of unknown reason. We analyzed also the results of laboratory tests C4, C1 inhibitor, C1q. In all cases the face was dominated localization. After the treatment of primary lymphoproliferive disease, in two cases, we observed total remission of angioedema. Only one patient with gammapathy require treatment with C1 inhibitor during the attacks. In these case we observed both plasma deriver, and recombinant C1 inhibitor were effective.

Clinical Features of Hereditary and Mast Cell-mediated Angioedema Focusing on the Differential Diagnosis in Japanese Patients.

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Ohsawa, Isao; Honda, Daisuke; Hisada, Atsuko; Inoshita, Hiroyuki; Onda-Tsueshita, Kisara; Mano, Satoshi; Sato, Nobuyuki; Nakamura, Yuya; Shimizu, Tatsuo; Gotoh, Hiromichi; Goto, Yoshikazu; Suzuki, Yusuke; Tomino, Yasuhiko

2018-02-01

Objective The present study was designed to identify the clinical characteristics that permit the differential diagnosis of hereditary angioedema (HAE) and mast cell-mediated angioedema (Mast-AE) during the first consultation. Methods The medical histories and laboratory data of 46 patients with HAE and 41 patients with Mast-AE were compared. Results The average age of onset in the HAE group (19.8±9.0 years) was significantly lower than that in the Mast-AE group (35.2±12.0 years). The incidence of familial angioedema (AE) in the HAE group (73.9%) was significantly higher than that in the Mast-AE group (9.7%). The frequency of history of AE in the extremities, larynx, or gastrointestinal tract was significantly higher in the HAE group. The frequency of AE episodes of the lips and eyelids was significantly lower in the HAE group. The serum C4 concentration and CH50 titer were lower than the normal limit in 91.3% and 45.6% of the patients in the HAE group, respectively; in Mast-AE group the serum C4 concentration and CH50 titer were significantly lower than the normal limit in 4.8% and 0% of the patients, the difference between the two groups was statistically significant. A C1-inhibitor (C1-INH) activity level of <50% was observed in all of the HAE patients, but none of the Mast-AE patients. The mean serum IgE titer in the HAE group (120.8±130.5 IU/mL) was significantly lower than that in the Mast-AE group (262.2±314.9 IU/mL). Conclusion The parameters within the patients' medical histories, such as the age at the onset of AE, a family history of AE, and the locations of past AE episodes are critical for the successful diagnosis of the disease. Measurements of the C4 and C1-INH activity are very useful for differential diagnosis of HAE from Mast-AE.

Optimum Use of Acute Treatments for Hereditary Angioedema: Evidence-Based Expert Consensus

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Hilary Longhurst

2018-03-01

Full Text Available Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients’ quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze, a recombinant C1 inhibitor (Ruconest/Conestat alpha, a kallikrein inhibitor (Ecallantide, and a bradykinin B2 receptor inhibitor (Icatibant are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophylactic agents are associated with breakthrough attacks, therefore an acute treatment plan is essential for every patient. Experience has shown that higher doses of C1 inhibitor than previously recommended may be desirable, although only recombinant C1 inhibitor has been subject to full dose–response evaluation. Treatment of early symptoms of an attack, with any licensed therapy, results in milder symptoms, more rapid resolution and shorter duration of attack, compared with later treatment. All therapies have been shown to be well-tolerated, with low risk of serious adverse events. Plasma-derived C1 inhibitors have a reassuring safety record regarding lack of transmission of virus or other infection. Thrombosis has been reported in association with plasma-derived C1 inhibitor in some case series. Ruconest was associated with anaphylaxis in a single rabbit-allergic volunteer, but no further anaphylaxis has been reported in those not allergic to rabbits despite, in a few cases, prior IgE sensitization to rabbit or milk protein. Icatibant is associated with high incidence of local reactions but not with systemic effects. Ecallantide may cause anaphylactoid reactions and is given under supervision. For children and pregnant women, plasma-derived C1 inhibitor has the best evidence of safety and currently remains first-line treatment.

Optimum Use of Acute Treatments for Hereditary Angioedema: Evidence-Based Expert Consensus.

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Longhurst, Hilary

2017-01-01

Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients' quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze), a recombinant C1 inhibitor (Ruconest/Conestat alpha), a kallikrein inhibitor (Ecallantide), and a bradykinin B2 receptor inhibitor (Icatibant) are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophylactic agents are associated with breakthrough attacks, therefore an acute treatment plan is essential for every patient. Experience has shown that higher doses of C1 inhibitor than previously recommended may be desirable, although only recombinant C1 inhibitor has been subject to full dose-response evaluation. Treatment of early symptoms of an attack, with any licensed therapy, results in milder symptoms, more rapid resolution and shorter duration of attack, compared with later treatment. All therapies have been shown to be well-tolerated, with low risk of serious adverse events. Plasma-derived C1 inhibitors have a reassuring safety record regarding lack of transmission of virus or other infection. Thrombosis has been reported in association with plasma-derived C1 inhibitor in some case series. Ruconest was associated with anaphylaxis in a single rabbit-allergic volunteer, but no further anaphylaxis has been reported in those not allergic to rabbits despite, in a few cases, prior IgE sensitization to rabbit or milk protein. Icatibant is associated with high incidence of local reactions but not with systemic effects. Ecallantide may cause anaphylactoid reactions and is given under supervision. For children and pregnant women, plasma-derived C1 inhibitor has the best evidence of safety and currently remains first-line treatment.

Evidence of impaired sense of smell in hereditary angioedema.

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Perricone, C; Agmon-Levin, N; Shoenfeld, N; de Carolis, C; Guarino, M D; Gigliucci, G; Milana, I; Novelli, L; Valesini, G; Perricone, R; Shoenfeld, Y

2011-01-01

Hereditary angioedema (HAE) is an autosomal-dominant disorder resulting from C1-inhibitor (C1INH) deficiency. Smell impairments were found in patients affected with systemic lupus erythematosus, that, similarly to HAE, is characterized by the activation of the classical complement pathway with C4 consumption. In this study, we aimed at evaluating the sense of smell in patients with HAE. Thirty patients with HAE and 30 healthy age- and sex-matched controls were evaluated for olfactory functions using the 3-stages Sniffin'-Sticks kit (threshold, discrimination, and identification [TDI]). TDI scores were analyzed according to complement levels (C1INH, C3, C4 and CH50), Beck depression inventory (BDI-II) and danazol treatment. A significant decrease in olfactory function was observed in patients affected with HAE compared with controls in total TDI score (P < 0.001), and in the discrimination (P < 0.001) and identification scores (P = 0.012). Anosmia was present only in patients with HAE (3.3%) who also exhibited more frequently hyposmia (53.3%vs 3.3%, P < 0.0001). Complement levels were reduced in patients with HAE. C4 serum levels showed positive correlation with total TDI score (P < 0.001), and with discrimination (P = 0.002) and identification (P = 0.011) scores. CH50 complement levels showed positive correlation with total TDI score (P < 0.001), and with threshold (P = 0.002) and discrimination (P = 0.011) scores. Sex, age, danazol treatment, BDI-II scores were not different between the patients and controls and did not influence TDI scores significantly. Evidence for an impaired sense of smell was found in patients with HAE. The reduction in olfactory function in these cases seems to correlate with complement C4 and CH50 levels. Immune and genetic mechanisms might play a role in this defect. © 2010 John Wiley & Sons A/S.

The Complex Interaction Between Polycystic Ovary Syndrome and Hereditary Angioedema: Case Reports and Review of the Literature.

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Iahn-Aun, Marina; Aun, Marcelo Vivolo; Motta, Antonio Abílio; Kalil, Jorge; Giavina-Bianchi, Pedro; Hayashida, Sylvia Asaka; Baracat, Edmund Chada; Maciel, Gustavo Arantes

2017-07-01

Hereditary angioedema (HAE) is a rare but severe disease, with high risk of death, and attacks have been associated to high estrogen levels. Polycystic ovary syndrome (PCOS) is a common hyperandrogenic condition, which is frequently treated with combined oral contraceptives. The aim of this study was to describe 2 clinical cases of young women diagnosed as having PCOS who developed HAE attacks after the introduction of combined estrogen-progestin pills to treat PCOS symptoms. Literature review of sex hormones' role in genesis of HAE attacks and possible mechanisms involved. In the cases reported, after initiation of combined contraceptives, patients presented with facial swelling with airway involvement (laryngeal edema) and abdominal pain. They had a familial history of angioedema and normal C1 inhibitor (C1-INH) levels, leading to the diagnosis of HAE with normal C1-INH (HAEnC1-INH) or HAE type III. After suspension of exogenous estrogen, patients remained asymptomatic from HAE. HAEnC1-INH is an estrogen-dependent form of HAE. It is well established that exogenous estrogen triggers attacks of all types of HAE. However, this is the first description of the association between PCOS and HAE, in which PCOS could be masking HAE symptoms. We propose that PCOS might have a protective role regarding HAE attacks, because of its particular hormonal features, that is, hyperandrogenism and relative stable levels of estradiol. The use of combined estrogen-progestin compounds in women with PCOS and HAE must be avoided, and treatment must be individualized.

Use of a C1 Inhibitor Concentrate in Adults ≥65 Years of Age with Hereditary Angioedema

DEFF Research Database (Denmark)

Bygum, Anette; Martinez-Saguer, Inmaculada; Bas, Murat

2016-01-01

BACKGROUND: Treatment of hereditary angioedema (HAE) in 'older adults' (those aged ≥65 years) has not been well studied. The international Berinert Patient Registry collected data on the use of intravenous plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH; Berinert......(®)/CSL Behring) in patients of any age, including many older adults. METHODS: This observational registry, conducted from 2010 to 2014 at 30 US and seven European sites, gathered prospective (post-enrollment) and retrospective (pre-enrollment) usage and adverse event (AE) data on subjects treated with pnfC1-INH....... RESULTS: The registry documented 1701 pnfC1-INH infusions in 27 older adults. A total of 1511 HAE attacks treated with pnfC1-INH administration were reported among 25 of the 27 (92.6 %) older adults. Among the older adults, mean (standard deviation [SD]) (8.8 [4.1] IU/kg) and median (6.4 IU/kg) pnfC1-INH...

Exposure‐Response Model of Subcutaneous C1‐Inhibitor Concentrate to Estimate the Risk of Attacks in Patients With Hereditary Angioedema

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Tortorici, Michael A.; Pawaskar, Dipti; Pragst, Ingo; Machnig, Thomas; Hutmacher, Matthew; Zuraw, Bruce; Cicardi, Marco; Craig, Timothy; Longhurst, Hilary; Sidhu, Jagdev

2018-01-01

Subcutaneous C1‐inhibitor (HAEGARDA, CSL Behring), is a US Food and Drug Administration (FDA)‐approved, highly concentrated formulation of a plasma‐derived C1‐esterase inhibitor (C1‐INH), which, in the phase III Clinical Studies for Optimal Management in Preventing Angioedema with Low‐Volume Subcutaneous C1‐inhibitor Replacement Therapy (COMPACT) trial, reduced the incidence of hereditary angioedema (HAE) attacks when given prophylactically. Data from the COMPACT trial were used to develop a repeated time‐to‐event model to characterize the timing and frequency of HAE attacks as a function of C1‐INH activity, and then develop an exposure–response model to assess the relationship between C1‐INH functional activity levels (C1‐INH(f)) and the risk of an attack. The C1‐INH(f) values of 33.1%, 40.3%, and 63.1% were predicted to correspond with 50%, 70%, and 90% reductions in the HAE attack risk, respectively, relative to no therapy. Based on trough C1‐INH(f) values for the 40 IU/kg (40.2%) and 60 IU/kg (48.0%) C1‐INH (SC) doses, the model predicted that 50% and 67% of the population, respectively, would see at least a 70% decrease in the risk of an attack. PMID:29316335

Hives and Angioedema

Science.gov (United States)

... is swelling or if you're having trouble breathing. Causes Hives and angioedema can be caused by: Foods. Many foods can trigger reactions in people with sensitivities. Shellfish, fish, peanuts, tree nuts, eggs and milk are frequent ...

Development and content validity testing of a patient-reported outcomes questionnaire for the assessment of hereditary angioedema in observational studies.

Science.gov (United States)

Bonner, Nicola; Abetz-Webb, Linda; Renault, Lydie; Caballero, Teresa; Longhurst, Hilary; Maurer, Marcus; Christiansen, Sandra; Zuraw, Bruce

2015-07-01

Hereditary Angioedema (HAE), a rare genetic disease, manifests as intermittent, painful attacks of angioedema. Attacks vary in frequency and severity and include skin, abdominal and life-threatening laryngeal swellings. This study aimed to develop a patient reported outcome (PRO) tool for the assessment of HAE attacks, including their management and impact on patients' lives, for use in clinical studies, or by physicians in general practice. The results of open-ended face to face concept elicitation interviews with HAE patients in Argentina (n = 10) and the US (n = 33) were used to develop the first draft questionnaire of the HAE patient reported outcomes questionnaire (HAE PRO). Subsequently, in-depth cognitive debriefing interviews were performed with HAE patients in the UK (n = 10), Brazil (n = 10), Germany (n = 11) and France (n = 12). Following input from eight multinational clinical experts further cognitive interviews were conducted in the US (n = 12) and Germany (n = 12). Patients who experienced abdominal, cutaneous or laryngeal attacks of varying severity levels were included in all rounds of interviews. Across the rounds of interviews patients discussed their HAE attack symptoms, impacts and treatments. Cognitive debriefing interviews explored patient understanding and relevance of questionnaire items. All interviews were conducted face to face following a pre-defined semi-structured interview guide in the patient's native language. Patients reported a variety of HAE symptoms, attack triggers, warning signs, attack impacts and treatment options which were used to develop the HAE PRO. The HAE PRO was revised and refined following input from patients and clinical experts. The final 18-item HAE PRO provides an assessment of the HAE attack experience including symptoms, impacts, treatment requirements, healthcare resource use and loss of productivity caused by HAE attacks. Patient and expert input has contributed to the

The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema

DEFF Research Database (Denmark)

Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette

2016-01-01

Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor...... concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema...

Patients perception of self-administrated medication in the treatment of hereditary angioedema.

Science.gov (United States)

Wang, Adrian; Fouche, Andrew; Craig, Timothy J

2015-08-01

Early therapy of hereditary angioedema (HAE) decreases morbidity, improves outcomes, decreases absenteeism, and possibly decreases mortality. This can be accomplished best with self-therapy. Previously, the authors examined barriers to self-therapy from the perspective of the nurse and the physician, but data are lacking on what patients perceive as major barriers to self-administered therapy for HAE. To identify those barriers in a prospective fashion by patient interview. After approval from the institutional review board, a telephone survey was performed of patients with HAE from a database of patients who were recently seen in the clinic. The survey focused on anxiety, depression, stress, concerns regarding method of administration, the ability to inject themselves, and what they perceived as barriers to providing self-care. Ninety-two patients were contacted and 59 agreed to participate. With 69% of those patients currently undergoing self-administered treatment, the results showed minimal depression and anxiety, a high satisfaction with treatment, and significant compliance with treatment. Most of those not yet on self-administered therapy wanted to start despite being satisfied with the care received in the emergency department. They also believed care at home would be optimal. The main concern of the 2 groups was not being able to treat themselves in the event of an HAE attack. From these data, it is obvious that most patients are willing to self-treat. This suggests that physicians should encourage self-treatment of HAE to improve outcomes and quality of life of patients with HAE. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Health-Related Quality of Life with Subcutaneous C1-Inhibitor for Prevention of Attacks of Hereditary Angioedema.

Science.gov (United States)

Lumry, William R; Craig, Timothy; Zuraw, Bruce; Longhurst, Hilary; Baker, James; Li, H Henry; Bernstein, Jonathan A; Anderson, John; Riedl, Marc A; Manning, Michael E; Keith, Paul K; Levy, Donald S; Caballero, Teresa; Banerji, Aleena; Gower, Richard G; Farkas, Henriette; Lawo, John-Philip; Pragst, Ingo; Machnig, Thomas; Watson, Douglas J

2018-01-31

Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) impairs health-related quality of life (HRQoL). The objective of this study was to assess HRQoL outcomes in patients self-administering subcutaneous C1-INH (C1-INH[SC]; HAEGARDA) for routine prevention of HAE attacks. Post hoc analysis of data from the placebo-controlled, crossover phase III COMPACT study (Clinical Studies for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy). Ninety patients with C1-INH-HAE were randomized to 1 of 4 treatment sequences: C1-INH(SC) 40 or 60 IU/kg twice weekly for 16 weeks, preceded or followed by 16 weeks of twice weekly placebo injections. All HAE attacks were treated with open-label on-demand treatment as necessary. HRQoL assessments at week 14 (last visit) included the European Quality of Life-5 Dimensions Questionnaire (EQ-5D-3L), the Hospital Anxiety and Depression Scale (HADS), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Treatment Satisfaction Questionnaire for Medication (TSQM). Compared with placebo (on-demand treatment alone), treatment with twice weekly C1-INH(SC) (both doses combined) was associated with better EQ-5D visual analog scale general health, less HADS anxiety, less WPAI presenteeism, work productivity loss, and activity impairment, and greater TSQM effectiveness and overall treatment satisfaction. More patients self-reported a "good/excellent" response during routine prevention with C1-INH(SC) compared with on-demand only (placebo prophylaxis) management. For each HRQoL measure, a greater proportion of patients had a clinically meaningful improvement during C1-INH(SC) treatment compared with placebo. In patients with frequent HAE attacks, a treatment strategy of routine prevention with self-administered twice weekly C1-INH(SC) had a greater impact on improving multiple HAE-related HRQoL impairments, most notably anxiety and work productivity, compared with on

Hereditary angioedema attacks resolve faster and are shorter after early icatibant treatment.

Directory of Open Access Journals (Sweden)

Marcus Maurer

Full Text Available BACKGROUND: Attacks of hereditary angioedema (HAE are unpredictable and, if affecting the upper airway, can be lethal. Icatibant is used for physician- or patient self-administered symptomatic treatment of HAE attacks in adults. Its mode of action includes disruption of the bradykinin pathway via blockade of the bradykinin B(2 receptor. Early treatment is believed to shorten attack duration and prevent severe outcomes; however, evidence to support these benefits is lacking. OBJECTIVE: To examine the impact of timing of icatibant administration on the duration and resolution of HAE type I and II attacks. METHODS: The Icatibant Outcome Survey is an international, prospective, observational study for patients treated with icatibant. Data on timings and outcomes of icatibant treatment for HAE attacks were collected between July 2009-February 2012. A mixed-model of repeated measures was performed for 426 attacks in 136 HAE type I and II patients. RESULTS: Attack duration was significantly shorter in patients treated <1 hour of attack onset compared with those treated ≥ 1 hour (6.1 hours versus 16.8 hours [p<0.001]. Similar significant effects were observed for <2 hours versus ≥ 2 hours (7.2 hours versus 20.2 hours [p<0.001] and <5 hours versus ≥ 5 hours (8.0 hours versus 23.5 hours [p<0.001]. Treatment within 1 hour of attack onset also significantly reduced time to attack resolution (5.8 hours versus 8.8 hours [p<0.05]. Self-administrators were more likely to treat early and experience shorter attacks than those treated by a healthcare professional. CONCLUSION: Early blockade of the bradykinin B(2 receptor with icatibant, particularly within the first hour of attack onset, significantly reduced attack duration and time to attack resolution.

Epidemiology of angioedema without wheals in an allergy and immunology center.

Science.gov (United States)

Malbrán, Eloisa; Fernández Romero, Diego; Juri, Maria Cecilia; Larrauri, Blas J; Malbrán, Alejandro

2015-01-01

We describe the diagnostic epidemiology, the clinical course, the family history and the response to treatment of patients with angioedema without wheals (AWW) at an Allergy and Immunology Clinical Center. We reviewed the case records of all patients at our office from January 1997 to April 2013. We recorded sex, age, age at onset of symptoms, family history of angioedema, number of visits to the office, type of angioedema, and response to treatment from those patients with angioedema without wheals. We classified angioedema according to its pathophysiology. We also describe those patients with angioedema mimics. From a total of 17,823 new patients, 303 had a presumptive diagnosis of angioedema without wheals. Twenty-three patients had an angioedema mimic. Forty percent were male and 60% were female. Average age at first visit was 40.6. Average number of visits was 2.4. Fifty-seven patients referred a family history. We attributed idiopathic angioedema to 55.7% of patients, 24.3% were drug related, 15.7% were due to C1 inhibitor deficiency, 2.1% were drug related+idiopathic angioedema, 1.4% were type III and 0.7% had exercise-induced angioedema. Ninety six percent of 53 evaluable idiopathic angioedema patients referred a benefit with anti-histamine therapy. AWW was a rare cause of consultation. Most of our patients had anti H1 responsive idiopathic angioedema and none had allergic angioedema. Women cases prevailed over men's. Family history and average age of onset of symptoms were different among the different types of angioedema.

Helicobacter pylori infection as a triggering factor of attacks in patients with hereditary angioedema

DEFF Research Database (Denmark)

Visy, Beáta; Füst, George; Bygum, Anette

2007-01-01

BACKGROUND: Helicobacter pylori infection is considered among the causative factors of urticaria and angioedema. Having conducted a study on 65 patients, Hungarian authors reported in 2001 that successful eradication of H. pylori is followed by a significant reduction in the number of attacks in ...

Recent Advances in Drug-Induced Angioedema

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Naoko Inomata

2012-01-01

Full Text Available Angioedema is the end result of deep dermal, subcutaneous and/or mucosal swelling, and is potentially a life- threatening condition in cases where the pharynx or larynx is involved. Drug-induced angioedema has been reported to occur in response to a wide range of drugs and vaccines. Drug-induced angioedema, like other cutaneous drug reactions, has been reported to be most frequently elicited by beta-lactam antibiotics and nonsteroidal anti-inflammatory drugs, although reliable data from epidemiologic studies are scarce. Recent reports suggested an increasing role of angiotensin-converting enzyme inhibitors (ACEIs in the causation of life- threatening angioedema. ACEI-related angioedema is never accompanied by urticaria and occurs via a kinin- dependent mechanism. ACEI-related angioedema not only can start years after beginning the treatment, but it can then recur irregularly while under that treatment. Furthermore, allergy tests are unreliable for the diagnosis of ACEI-related angioedema, and so the relationship between angioedema and ACEIs is often missed and consequently quite underestimated. Accordingly, better understanding of the kinin-dependent mechanism, which is particular to angioedema, is necessary for the appropriate management of drug-induced angioedema.

The humanistic burden of hereditary angioedema: results from the Burden of Illness Study in Europe.

Science.gov (United States)

Caballero, Teresa; Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Wait, Suzanne; Boysen, Henrik B

2014-01-01

Hereditary angioedema (HAE) is a rare but potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The broad range of consequences of HAE on patients' lives is not well understood. The study objective was to comprehensively characterize the burden of illness and impact of HAE types I and II from the patient perspective. The HAE Burden of Illness Study in Europe was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective via a one-time survey, which included items on clinical characteristics and physical and emotional impacts. One hundred eighty-six patients participated; 59% reported having an attack at least once a month, 67% reported moderate-to-severe pain during their last attack, and 74% reported moderate-to-severe swelling. The most common sites of the last attack were the abdomen and extremities; 24% experienced an attack in more than one site. The impact of HAE on daily activities was high during attacks and did not vary significantly by body site affected; patients also reported that HAE impacted their daily activities between attacks. Patients reported substantial anxiety about future attacks, traveling, and passing HAE to their children. Based on Hospital Anxiety and Depression Scale scores, 38 and 14% had clinically meaningful anxiety and depression, respectively. Despite standard of care, HAE patients still have frequent and painful attacks. Patients experience substantial impairment physically and emotionally both during and between attacks. A better understanding of these effects may help in the clinical management of HAE patients.

The humanistic burden of hereditary angioedema: Impact on health-related quality of life, productivity, and depression.

Science.gov (United States)

Lumry, William R; Castaldo, Anthony J; Vernon, Margaret K; Blaustein, Marc B; Wilson, David A; Horn, Patrick T

2010-01-01

Hereditary angioedema (HAE) is a rare, autosomal dominant disorder characterized by recurrent acute attacks of swelling of the larynx, abdomen, and periphery. This study was designed to assess the humanistic burden of illness associated with HAE. HAE burden was assessed via a web-based survey of patients that solicited information on attack characterization, treatment, side effects, pain, and functional and emotional burden of disease management. In addition to HAE-specific sections, the survey used three standardized instruments to compare HAE patient data to normative (healthy) and chronic disease populations: the 12-Item Short Form (SF-12) Health Survey, the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire, and the Hamilton Depression Inventory-Short Form (HDI-SF). A total of 457 HAE patients responded to the survey (response rate, ∼19%). Patients reported significantly poorer health-related quality of life versus population norms, based on the SF-12 Physical Component Summary (mean, 43.7 versus 49.6; p 8.5, indicative of depressive symptomatology. Productivity was also markedly impaired in all WPAI-GH categories, including 34% overall work impairment. Because of their most recent HAE attack, workers lost a mean of 3.3 days; students lost a mean of 1.9 days. HAE results in considerable humanistic burden to patients across physical and mental health domains; negatively impacts education, career, and work productivity; and compounds the substantial economic burdens that are reported separately.

ACE-I Angioedema: Accurate Clinical Diagnosis May Prevent Epinephrine-Induced Harm

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R. Mason Curtis

2016-06-01

Full Text Available Introduction: Upper airway angioedema is a life-threatening emergency department (ED presentation with increasing incidence. Angiotensin-converting enzyme inhibitor induced angioedema (AAE is a non-mast cell mediated etiology of angioedema. Accurate diagnosis by clinical examination can optimize patient management and reduce morbidity from inappropriate treatment with epinephrine. The aim of this study is to describe the incidence of angioedema subtypes and the management of AAE. We evaluate the appropriateness of treatments and highlight preventable iatrogenic morbidity. Methods: We conducted a retrospective chart review of consecutive angioedema patients presenting to two tertiary care EDs between July 2007 and March 2012. Results: Of 1,702 medical records screened, 527 were included. The cause of angioedema was identified in 48.8% (n=257 of cases. The most common identifiable etiology was AAE (33.1%, n=85, with a 60.0% male predominance. The most common AAE management strategies included diphenhydramine (63.5%, n=54, corticosteroids (50.6%, n=43 and ranitidine (31.8%, n=27. Epinephrine was administered in 21.2% (n=18 of AAE patients, five of whom received repeated doses. Four AAE patients required admission (4.7% and one required endotracheal intubation. Epinephrine induced morbidity in two patients, causing myocardial ischemia or dysrhythmia shortly after administration. Conclusion: AAE is the most common identifiable etiology of angioedema and can be accurately diagnosed by physical examination. It is easily confused with anaphylaxis and mismanaged with antihistamines, corticosteroids and epinephrine. There is little physiologic rationale for epinephrine use in AAE and much risk. Improved clinical differentiation of mast cell and non-mast cell mediated angioedema can optimize patient management.

Disease: H01006 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available H01006 Hereditary angioedema Hereditary angioedema (HAE) is a rare genetic disorde...r, manifested by recurrent episodes of angioedema localized to the skin or mucosa of the gastrointestinal tr...act or larynx. The laryngeal angioedema is potentially lethal. The classic forms, HAE types I and II, result...6100 PMID:14572810 (description, gene) ... AUTHORS ... Davis AE 3rd ... TITLE ... The pathogenesis of hereditary angioedema... (drug) ... AUTHORS ... Antoniu SA ... TITLE ... Therapeutic approaches in hereditary angioedema. ... JOURNAL ... Clin

The hereditary angioedema burden of illness study in Europe (HAE-BOIS-Europe: background and methodology

Directory of Open Access Journals (Sweden)

Bygum Anette

2012-04-01

Full Text Available Abstract Background Hereditary angioedema (HAE is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation. While there have been major advancements in our understanding of the immunogenetics of HAE, there are significant gaps in the literature regarding understanding of the humanistic and economic impact of the disease, particularly in Europe. The purpose of the HAE Burden of Illness Study-Europe (HAE-BOIS-Europe, the development and methodology of which is described here, is to better understand the management and impact of HAE from the patient perspective in Europe. Methods/Design This is a cross-sectional study in which retrospective data were also collected being conducted in Denmark, Germany and Spain. The study is open to patients ages 12 and older with a diagnosis of HAE-I or HAE-II. Data collection includes: (i a survey on individuals’ health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale; and (ii one-on-one interviews to collect detailed descriptive data and patient testimonials on the impact of HAE on patients’ health-related quality of life. Discussion The present manuscript describes the development and plans for implementing a multi-country European study with the aim of characterizing the humanistic and economic burden of HAE from the patient perspective. This study will help raise awareness of HAE as a rare but debilitating condition with wide-ranging impacts.

The hereditary angioedema burden of illness study in Europe (HAE-BOIS-Europe): background and methodology.

Science.gov (United States)

Bygum, Anette; Aygören-Pürsün, Emel; Caballero, Teresa; Beusterien, Kathleen; Gholizadeh, Shadi; Musingarimi, Patience; Wait, Suzanne; Boysen, Henrik

2012-04-26

Hereditary angioedema (HAE) is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation. While there have been major advancements in our understanding of the immunogenetics of HAE, there are significant gaps in the literature regarding understanding of the humanistic and economic impact of the disease, particularly in Europe. The purpose of the HAE Burden of Illness Study-Europe (HAE-BOIS-Europe), the development and methodology of which is described here, is to better understand the management and impact of HAE from the patient perspective in Europe. This is a cross-sectional study in which retrospective data were also collected being conducted in Denmark, Germany and Spain. The study is open to patients ages 12 and older with a diagnosis of HAE-I or HAE-II. Data collection includes: (i) a survey on individuals' health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale); and (ii) one-on-one interviews to collect detailed descriptive data and patient testimonials on the impact of HAE on patients' health-related quality of life. The present manuscript describes the development and plans for implementing a multi-country European study with the aim of characterizing the humanistic and economic burden of HAE from the patient perspective. This study will help raise awareness of HAE as a rare but debilitating condition with wide-ranging impacts.

Ticagrelor-Induced Angioedema: A Rare and Unexpected Phenomenon

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Rajeev Seecheran

2017-01-01

Full Text Available Angioedema can cause potentially life-threatening airway obstruction. This case report describes an exceedingly rare episode of ticagrelor-induced hypersensitivity reaction, manifesting as angioedema with periorbital and likely respiratory involvement. The heart team should be vigilant for this precarious condition which may require emergent airway management. Desensitization protocols and alternative regimens (e.g., clopidogrel, prasugrel, and addition of an adjunctive anticoagulant should be considered when there is an absolute indication for antiplatelet therapy.

Dipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema

OpenAIRE

Byrd, James Brian; Touzin, Karine; Sile, Saba; Gainer, James V.; Yu, Chang; Nadeau, John; Adam, Albert; Brown, Nancy J.

2007-01-01

Angioedema is a potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors. Bradykinin and substance P, substrates of angiotensin-converting enzyme, increase vascular permeability and cause tissue edema in animals. Studies indicate that amino-terminal degradation of these peptides, by aminopeptidase P and dipeptidyl peptidase IV, may be impaired in individuals with angiotensin-converting enzyme inhibitor–associated angioedema. This case-control study tested the hy...

Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks: prospective experimental single-cohort study.

Science.gov (United States)

Campos, Regis Albuquerque; Valle, Solange Oliveira Rodrigues; França, Alfeu Tavares; Cordeiro, Elisabete; Serpa, Faradiba Sarquis; Mello, Yara Ferreira; Malheiros, Teresinha; Toledo, Eliana; Mansour, Elie; Fusaro, Gustavo; Grumach, Anete Sevciovic

2014-01-01

Hereditary angioedema (HAE) with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil. Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients. Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored. 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age). The symptoms were: subcutaneous edema (22/24); abdominal pain (15/24) and upper airway obstruction (10/24). The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%); 10-20 (5/24; 20.8%); 20-30 (8/24; 33.4%); 30-60 (5/24; 20.8%); and 2 hours (1/24; 4.3%). The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6. HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.

Acute dystonic reaction leading to lingual hematoma mimicking angioedema

Science.gov (United States)

Sezer, Özgür; Aydin, Ali Attila; Bilge, Sedat; Arslan, Fatih; Arslan, Hasan

2017-01-01

Lingual hematoma is a severe situation, which is rare and endangers the airway. It can develop due to trauma, vascular abnormalities, and coagulopathy. Due to its sudden development, it can be clinically confused with angioedema. In patients who applied to the doctor with complaints of a swollen tongue, lingual hematoma can be confused with angioedema, in particular, at the beginning if the symptoms occurred after drug use. It should especially be considered that dystonia in the jaw can present as drug-induced hyperkinetic movement disorder. Early recognition of this rare clinical condition and taking precautions for providing airway patency are essential. In this case report, we will discuss mimicking angioedema and caused by a bite due to dystonia and separation of the tongue from the base of the mouth developing concurrently with lingual hematoma. PMID:29326495

Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks: prospective experimental single-cohort study

Directory of Open Access Journals (Sweden)

Regis Albuquerque Campos

Full Text Available CONTEXT AND OBJECTIVE: Hereditary angioedema (HAE with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil.DESIGN AND SETTING: Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients.METHODS: Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored.RESULTS: 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age. The symptoms were: subcutaneous edema (22/24; abdominal pain (15/24 and upper airway obstruction (10/24. The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%; 10-20 (5/24; 20.8%; 20-30 (8/24; 33.4%; 30-60 (5/24; 20.8%; and 2 hours (1/24; 4.3%. The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6.CONCLUSION: HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.

Trifluoperazine-Induced Angioedema

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Mugtaba Osman

2014-01-01

Full Text Available Angioedema is a serious adverse drug reaction that can rarely be associated with trifluoperazine treatment. We present the case of a 44-year-old male with an established diagnosis of schizoaffective disorder, for which trifluoperazine therapy was considered. He presented to the emergency department with bilateral lower limb oedematous painful erythematous swelling that eased off completely when trifluoperazine was stopped. The possibility of allergic reaction, such as angioedema, should always be kept in mind by psychiatrists and mental health professionals when prescribing trifluoperazine antipsychotic.

International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency.

Science.gov (United States)

Farkas, H; Martinez-Saguer, I; Bork, K; Bowen, T; Craig, T; Frank, M; Germenis, A E; Grumach, A S; Luczay, A; Varga, L; Zanichelli, A

2017-02-01

The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1-INH-HAE. During an expert panel meeting that took place during the 9th C1 Inhibitor Deficiency Workshop in Budapest, 2015 (www.haenet.hu), pediatric data were presented and discussed and a consensus was developed by voting. The symptoms of C1-INH-HAE often present in childhood. Differential diagnosis can be difficult as abdominal pain is common in pediatric C1-INH-HAE, but also commonly occurs in the general pediatric population. The early onset of symptoms may predict a more severe subsequent course of the disease. Before the age of 1 year, C1-INH levels may be lower than in adults; therefore, it is advisable to confirm the diagnosis after the age of one year. All neonates/infants with an affected C1-INH-HAE family member should be screened for C1-INH deficiency. Pediatric patients should always carry a C1-INH-HAE information card and medicine for emergency use. The regulatory approval status of the drugs for prophylaxis and for acute treatment is different in each country. Plasma-derived C1-INH, recombinant C1-INH, and ecallantide are the only agents licensed for the acute treatment of pediatric patients. Clinical trials are underway with additional drugs. It is recommended to follow up patients in an HAE comprehensive care center. The pediatric-focused international consensus for the diagnosis and management of C1-INH-HAE patients was created. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

Positive impact of omalizumab on angioedema and quality of life in patients with refractory chronic idiopathic/spontaneous urticaria: analyses according to the presence or absence of angioedema.

Science.gov (United States)

Maurer, M; Sofen, H; Ortiz, B; Kianifard, F; Gabriel, S; Bernstein, J A

2017-06-01

Approximately 50% of patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) report hives and angioedema; some experience hives/angioedema only. Assess omalizumab's effect on angioedema and quality of life (QoL) in subgroups with refractory CIU/CSU: those with and without angioedema. Patients received omalizumab (75, 150 or 300 mg) or placebo every 4 weeks for 12/24 weeks. Angioedema and QoL were assessed [Urticaria Patient Daily Diary and Dermatology Quality of Life Index (DLQI)]. Subgroups were based on the presence/absence of baseline angioedema 7 days prior to randomization. Patients with baseline angioedema randomized to omalizumab 300 mg had a greater reduction in mean weekly incidence of angioedema and mean number of days/week with angioedema vs. placebo at 12 and 24 weeks. A 3.3- to 4.5-point greater mean reduction in DLQI score was achieved with omalizumab 300 mg treatment vs. placebo, above the minimal clinically important difference threshold. Results with lower doses vs. placebo were variable. Compared with placebo, omalizumab 300 mg treatment over 12-24 weeks resulted in marked reduction in incidence and number of days/week with angioedema accompanied by clinically relevant improvement in QoL. © 2016 European Academy of Dermatology and Venereology.

Assessment of 105 Patients with Angiotensin Converting Enzyme-Inhibitor Induced Angioedema

DEFF Research Database (Denmark)

Rasmussen, Eva Rye; von Buchwald, Christian; Wadelius, Mia

2017-01-01

Objective. To asses a cohort of 105 consecutive patients with angiotensin converting enzyme-inhibitor induced angioedema with regard to demographics, risk factors, family history of angioedema, hospitalization, airway management, outcome, and use of diagnostic codes used for the condition. Study...... gender was associated with a significantly higher risk of angiotensin converting enzyme-inhibitor induced angioedema. 6.7% had a positive family history of angioedema. Diabetes seemed to be a protective factor with regard to angioedema. 95% experienced angioedema of the head and neck. 4.7% needed...... Design. Cohort study. Methods. This was a retrospective cohort study of 105 patients with angiotensin converting enzyme-inhibitor induced angioedema in the period 1995-2014. Results. The cohort consisted of 67 females and 38 males (F : M ratio 1.8), with a mean age of 63 [range 26-86] years. Female...

How Not to Be Misled by Disorders Mimicking Angioedema

DEFF Research Database (Denmark)

Andersen, Michelle Fog; Longhurst, Hilary J; Rasmussen, Eva Rye

2016-01-01

BACKGROUND: Angioedema is a vascular reaction involving the lower dermis, subcutis and/or submucosal tissue and causing a temporary localized swelling in any part of the body. For many health care professionals, the diagnosis presents an ongoing challenge; several disorders may manifest with subc...

Angioedema Spotlight: A Closer Examination of Sacubitril/Valsartan Safety Results.

Science.gov (United States)

Owens, Ryan E; Oliphant, Carrie S

2017-01-01

Incorporation of neprilysin inhibition into heart failure pharmacotherapy regimens has recently been recommended by U.S. guidelines, based on results from the PARADIGM-HF trial comparing sacubitril/valsartan to enalapril. While most of the discussion has focused on efficacy, a closer examination of the safety results, particularly the incidence of angioedema during the run-in and double-blind periods, is also warranted. Although no major safety concerns were identified, an angioedema risk comparable to enalapril was found, primarily in the black population. Therefore, despite combination with an angiotensin receptor blocker, which historically has a lower incidence of angioedema, the addition of neprilysin inhibition yields an angioedema risk profile comparable to angiotensin converting enzyme (ACE) inhibitors. Clinicians should recognize this safety risk when prescribing sacubitril/valsartan and remain vigilant in counseling patients regarding the signs and symptoms of angioedema. As recommended by the guidelines, avoiding sacubitril/valsartan use concurrently or within 36 hours of the last dose of an ACE inhibitor or in patients with a history of angioedema is also crucial to minimize angioedema risk and prevent patient harm. © Copyright 2017 by the American Board of Family Medicine.

Bowel Angioedema Associated With Iodinated Contrast Media: Incidence and Predisposing Factors.

Science.gov (United States)

Seo, Nieun; Chung, Yong Eun; Lim, Joon Seok; Song, Mi Kyung; Kim, Myeong-Jin; Kim, Ki Whang

2017-09-01

Bowel angioedema is an acute adverse reaction to iodinated contrast media (CM) that involves the gastrointestinal tract. We aimed to investigate the incidence and predisposing factors of iodinated CM-associated bowel angioedema during computed tomography (CT) examinations. This study was approved by our institutional review board, and informed consent was waived due to its retrospective design. From July 2013 to July 2015, adult patients with a history of adverse reactions to iodinated CM during CT (group A, n = 427) and patients without adverse reactions matched for age and sex with the propensity-score matching method (group B, n = 427) were studied. Contrast media-associated bowel angioedema was determined when bowel wall thickness increased after contrast enhancement compared with the precontrast scan. Potential predisposing factors including patient demographics, symptoms and time of adverse reactions, and CM-related factors were compared between patients with and without angioedema in group A. In addition, the incidence of bowel angioedema was compared between groups A and B. The incidence of CM-associated bowel angioedema in group A was 3.3% (14/427) in the per-patient analysis and 2.6% (15/578) in the per-examination analysis. The CM-associated bowel angioedema involved the distal duodenum and/or proximal jejunum and showed long-segmental circumferential bowel wall thickening on CT. None of the studied predisposing factors was different between patients with and without bowel angioedema (P > 0.05). The incidence of CM-associated bowel angioedema in group B was 1.9% (8/427) and 1.7% (8/458) for per-patient and per-examination analyses, respectively, and these rates were not significantly different between groups A and B (P = 0.346 and P = 0.370, respectively). The incidence of CM-associated bowel angioedema during CT was 1.7% to 3.3%, and none of the studied predisposing factors was associated with bowel angioedema.

Angioedema adquirido autoimune de difícil controle em paciente com lúpus eritematoso sistêmico Intractable acquired autoimmune angioedema in a patient with systemic lupus erythematosus

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Vilson Furlanetto Junior

2010-02-01

Full Text Available O angioedema adquirido é causado por diferentes medicamentos e doenças linfoproliferativas, e tem sido raramente relacionado com a presença de doenças autoimunes. Descrevemos aqui uma paciente de 47 anos com lúpus eritematoso sistêmico (LES com envolvimento cutâneo importante que desenvolveu angioedema recorrente localizado em face incluindo lábios e pálpebras, membros superiores e tórax, não acompanhado de urticária e com dosagem do inibidor de C1 esterase reduzida. A utilização de antimaláricos, glicocorticoides e pulsoterapia com metilprednisolona associada ao uso de azatioprina não determinou melhora. A paciente utilizou também danazol sem sucesso, e apresentou resposta clínica somente após ter sido submetida a múltiplas sessões de plasmaferese, ocorrendo inclusive resolução de extenso angioedema na mucosa do trato gastrointestinal.Acquired angioedema is caused by different drugs and lymphoproliferative diseases, and rarely it has also been related to the presence of auto-immune disorders. We report the case of a 47 year old female with systemic lupus erythematosus (SLE and severe cutaneous involvement who developed recurrent localized angioedema of the face, including lips and eye lids, upper limbs, and thorax, not associated with urticaria, and with reduced levels of C1 esterase inhibitor. Treatment with antimalarials, glucocorticoids, and pulse therapy with methylprednisolone associated with azathioprine did not improve her condition. The patient was also unsuccessfully treated with danazol, and she only showed clinical response after several sessions of plasmapheresis, including resolution of the extensive edema of the gastrointestinal tract.

Disease: H00106 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available : C1 inhibitor deficiency (hereditary angioedema); C4 binding protein alpha deficiency; C4 binding protein b... subcutaneous and submucosal layers, identified as angioedema (hereditary or acquired). Genetic deficiency o

Urticaria and angioedema – more than just skin deep! | Holtzhausen ...

African Journals Online (AJOL)

Urticaria and angioedema are characterized by pruritic hives and sometimes swelling of deeper mucocutaneous layers. Urticaria is caused by release of histamine and other mediators from mast cells. A cut-off of six weeks distinguishes acute and chronic forms, as these seem to differ regarding etiological and response ...

Hypovolemic Shock Caused by Angiotensin-Converting Enzyme Inhibitor-Induced Visceral Angioedema: A Case Series and A Simple Method to Diagnose this Complication in the Emergency Department.

Science.gov (United States)

Myslinski, Joseph; Heiser, Andrew; Kinney, Ashley

2018-03-01

Visceral angioedema is a rarely reported side effect of angiotensin-converting-enzyme inhibitors (ACEI). Because signs and symptoms tend to be nonspecific, the diagnosis is difficult to make, especially in the emergency department (ED). We describe 2 patients presenting with signs of hypovolemic shock, in which the diagnosis of ACEI-induced visceral angioedema was made in the ED. We surmise that patients with abdominal pain, who present with hypovolemic shock and are taking medications that can predispose to angioedema, may have this complication if their hemoglobin level is elevated compared with their previous levels. An abdominal computed tomography scan, if it does not identify any other significant etiology, will increase the probability that ACEI-induced visceral angioedema is the diagnosis when there is nonspecific bowel wall thickening or edema. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Identification of ACEI-induced visceral angioedema in the ED will avoid prolonged admissions, unnecessary procedures, and future recurrences. Copyright © 2017 Elsevier Inc. All rights reserved.

Recurrent Laryngeal Edema Imitating Angioedema Caused by Dislocated Screw after Anterior Spine Surgery

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Piotr Wójtowicz

2015-01-01

Full Text Available The anterior cervical spine surgery is a common procedure to stabilize vertebrae damaged by various diseases. The plates and screws are usually used in the spine fixation. This kind of instrumentation may detach from the bones which is a rare but well-known complication. A 77-year-old male presented to the otorhinolaryngology department with throat pain, choking, and dysphagia. At first the angioedema was diagnosed and he was treated conservatively. The endoscopy revealed laryngeal edema, being more defined on the right side with right vocal fold paresis. CT scans showed the stabilizing plate with two screws attached tightly and the back-out of the third screw toward soft tissue of the neck. In the meantime, his condition deteriorated and he needed tracheotomy. In few days the surgical removal of the dislocated screw was performed successfully. Although two-month follow-up reported no obstruction of the larynx, the vocal folds paresis with gradual functional improvement was observed. Long-term complication of anterior spine surgery sometimes may suggest laryngeal angioedema at first. If the conservative treatment is ineffective and there is a history of anterior spine surgery, the clinicians should consider the displacement of the plate or screws in differential diagnosis.

Type I anaphylactic reaction due to contrast induced angioedema causing neck swelling: the role of sitting fiberoptic bronchoscopy in emergent intubation

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Ali Dabbagh

2016-07-01

Full Text Available Contrast induced angioedema is a rapidly progressive state involving a number of organ systems including the upper airway tract; which is usually a type I anaphylactic reaction also known as immediate hypersensitivity reaction. Prompt preservation of the respiratory tract is the cornerstone of this situation. The use of fiberoptic bronchoscope for tracheal intubation though very helpful, has some special considerations due to the anatomic distortions created by edema.This manuscript describes a patient with contrast induced angioedema managed successfully. Serum levels of IgE were highly increased during the first hours after the event; while serum levels of complement were normal. However, rapid airway management and prophylactic intubation saved the patient and prevented the possible aftermath of airway obstruction.Keywords: airway management; type I anaphylactic reaction, angioedema; fiberoptic bronchoscope.Conflict of interest: none of the authors has any conflict of interest.

Angiodema due to oral acitretin and isotretinoin Angioedema por acitretina e isotretinoína oral

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Roberto Rheingantz da Cunha Filho

2011-08-01

Full Text Available Angioedema may be caused by nonsteroidal antiinflammatory drugs, angiotensin- converting enzyme inhibitors, radiocontrast media, antibiotics, sea food etc. It can involve an allergic (IgE-mediated or non-allergic hypersensitivity reaction, both with a similar clinical presentation. While angioedema due to isotretionin has been described previously, this is the first description of angiodema due to acitretin. We report two uncommon cases of palpebral and labial angiodema due to retinoids, by acitretin and oral isotretinoin respectively: a 48-year-old man with psoriasis and a 24-year-old woman with severe acne resistant to antibiotics and topical drugs. In both cases the reaction persisted through-out treatment with these drugs, but resolved quickly after discontinuation. Reintroduction of the drugs brought on angioedema againAngioedema pode ser causado por diversos fármacos como : antiinflamatórios não-esteroidais, inibidores da ECA, contrastes, antibióticos e frutos do mar, entre outras causas. Pode ser uma reação alérgica, mediada por IgE, ou não-alérgica, com apresentações clínicas semelhantes. Angioedema por isotretinoína já foi relatado, mas não por acitretina. Relatamos dois casos, uma com angioedema palpebral e um labial, por acitretina e isotretinoína, respectivamente: um paciente de 48 anos com psoríase e uma paciente de 24 anos com acne resistente à terapia convencional. Em ambos casos a afecção persistiu durante o tratamento, resolveu com a interrupção e recidivou com reexposição

Clinical characteristics and treatment of chronic urticaria and angioedema : Dwelling on swelling, dealing with whealing

OpenAIRE

van den Elzen, M.T.

2017-01-01

The occurrence of wheals, angioedema or both for at least 6 weeks is diagnosed as chronic spontaneous urticaria in (inter) national guidelines - after excluding other illnesses. The underlying mechanism of angioedema without wheals is not entirely known. The objective of this thesis is to increase insight in the treatment of adult patients with angioedema with or without urticaria, and with urticaria with or without angioedema. We first studied patients with angioedema: we show that bradykini...

Inhalant abuse of computer cleaner manifested as angioedema.

Science.gov (United States)

Kurniali, Peter C; Henry, Letitia; Kurl, Rita; Meharg, Joseph V

2012-01-01

Inhalant abuse is the intentional inhalation of chemical vapors or volatile substance to achieve a euphoric effect. Although no statistical data are reported yet, inhalant abuse is potentially life-threatening and has resulted in a wide range of toxic effects such as central nervous system depression, seizures, aspiration, cardiac arrhythmia, asphyxiation, hypoxia, metabolic acidosis, and sudden death among others. We are reporting a 25-year-old white man who was brought to the emergency department after inhaling aerosolized computer-cleaning spray composed of difluoroethane. He was found to have marked upper and lower lip facial swelling consistent with angioedema. The patient also had a prolonged QT interval, mild inspiratory stridor, but no urticaria. In this case, we believe the difluoroethane-related angioedema represents either idiopathic or bradykinin-induced angioedema.

Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.

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Federica Defendi

Full Text Available BACKGROUND: The kinins (primarily bradykinin, BK represent the mediators responsible for local increase of vascular permeability in hereditary angioedema (HAE, HAE I-II associated with alterations of the SERPING1 gene and HAE with normal C1-Inhibitor function (HAE-nC1INH. Besides C1-Inhibitor function and concentration, no biological assay of kinin metabolism is actually available to help physicians for the diagnosis of angioedema (AE. We describe enzymatic tests on the plasma for diagnosis of BK-dependent AE. METHODS: The plasma amidase assays are performed using the Pro-Phe-Arg-p-nitroanilide peptide substrate to evaluate the spontaneous amidase activity and the proenzyme activation. We analyzed data of 872 patients presenting with BK-dependent AE or BK-unrelated diseases, compared to 303 controls. Anti-high MW kininogen (HK immunoblot was achieved to confirm HK cleavage in exemplary samples. Reproducibility, repeatability, limit of blank, limit of detection, precision, linearity and receiver operating characteristics (ROC were used to calculate the diagnostic performance of the assays. RESULTS: Spontaneous amidase activity was significantly increased in all BK-dependent AE, associated with the acute phase of disease in HAE-nC1INH, but preserved in BK-unrelated disorders. The increase of the amidase activity was associated to HK proteolysis, indicating its relevance to identify kininogenase activity. The oestrogens, known for precipitating AE episodes, were found as triggers of enzymatic activity. Calculations from ROC curves gave the optimum diagnostic cut-off for women (9.3 nmol⋅min(-1⋅mL(-1, area under curve [AUC] 92.1%, sensitivity 80.0%, and specificity 90.1% and for men (6.6 nmol·min(-1⋅mL(-1, AUC 91.0%, sensitivity 87.0% and specificity 81.2%. CONCLUSION: The amidase assay represents a diagnostic tool to help physicians in the decision to distinguish between BK-related and -unrelated AE.

Angioedema recorrente – caso clínico

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Sandrina Martins

2016-02-01

Full Text Available Introdução: O Angioedema hereditário (AEH é uma causa rara de angioedema recorrente, resultante de um defeito a nível do gene que codifica o inibidor do C1 esterase (C1 -INH. O edema envolve predominantemente os tecidos da face, membros, trato gastrointestinal e área genital. O envolvimento da laringe, apesar de menos frequente, constitui a expressão clínica mais grave, sendo potencialmente fatal. Caso clínico: Descreve -se o caso clínico de uma criança do sexo feminino de oito anos de idade referenciada à consulta de pediatria por episódios recorrentes de angioedema. O estudo efetuado revelou tratar -se de um caso de AEH. Discussão: O diagnóstico, estabelecido com base no quadro clínico, estudo do complemento e história familiar, é de importância fundamental considerando que o AEH é potencialmente fatal e exige uma terapêutica específica.

Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions.

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Rémi Baroso

Full Text Available Angioedema without wheals (AE is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh, but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases.We wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker.We retrospectively investigated high molecular weight kininogen (HK cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis.Circulating native HK plasma concentrations were similar in the healthy men (interquartile range: 98-175μg/mL, n = 51 and in healthy women (90-176μg/mL, n = 74, while HK cleavage was lower (p14.4% HK cleavage for men; 33.0% HK cleavage for women, with >98% specificity achieved for all parameters. In plasma from patients undergoing recovery two months after oestrogen/progestin combination withdrawal (n = 13 or two weeks after AE attack (n = 2, HK cleavage was not fully restored, suggesting its use as a post-attack assay.As a diagnostic tool, HK cleavage can offer physicians supportive arguments for kinin production in suspected AE cases and improve patient follow-up in clinical trials or prophylactic management.

Suspected tartrazine-induced acute urticaria/angioedema is only rarely reproducible by oral rechallenge.

Science.gov (United States)

Nettis, E; Colanardi, M C; Ferrannini, A; Tursi, A

2003-12-01

Tartrazine has been frequently linked to several diseases. However, a cause-and-effect role for tartrazine in these illnesses, especially in urticaria, has not always been established. The aim of this study is to determine the incidence of intolerance to tartrazine among subjects who experienced an acute episode of urticaria/angioedema following the ingestion of a meal or a product containing this substance. This was a retrospective study based on analysis of data of patients reported to have experienced episodes of urticaria and/or angioedema after ingesting meals or products containing tartrazine. At the first visit to the outpatients clinic, a careful anamnesis had been taken. Patients had then been submitted to the following diagnostic tests: IgE tests to common inhalant allergens and food allergens and a double-blind placebo-controlled challenge with tartrazine. A total of 102 subjects were enrolled in the study: 19 (18.6%) showed at least one relevant positive reaction to an IgE test for food allergy. Only one subject (1%) had reactions after ingestion of 5 mg of tartrazine, given on day 5. She did not have adverse reactions to placebo. This study shows that the percentage of acute urticaria and/or angioedema induced by tartrazine is very low (1%). In view of our results, we suggest that all physicians with patients who have suffered adverse reactions that could be attributed to tartrazine should also carefully evaluate other possible causes.

Effectiveness of icatibant for treatment of hereditary angioedema attacks is not affected by body weight: findings from the Icatibant Outcome Survey, a cohort observational study.

Science.gov (United States)

Caballero, Teresa; Zanichelli, Andrea; Aberer, Werner; Maurer, Marcus; Longhurst, Hilary J; Bouillet, Laurence; Andresen, Irmgard

2018-01-01

Icatibant is a bradykinin B2-receptor antagonist used for the treatment of hereditary angioedema attacks resulting from C1-inhibitor deficiency. Treatment is not adjusted by body weight however the impact of body mass index (BMI) on the effectiveness of icatibant is not documented in the literature. We examined disease characteristics and icatibant treatment effectiveness in patients stratified by BMI in the Icatibant Outcome Survey, an ongoing, international, observational study monitoring the real-world safety and effectiveness of icatibant. Attack and treatment characteristics as well as outcomes following treatment with icatibant were compared among patients with underweight, normal, overweight, and obese BMI. Data from 2697 icatibant-treated attacks in 342 patients (3.5, 44.7, 34.8, and 17.0% patients of underweight, normal, overweight, and obese BMI, respectively) were analyzed. There was no significant difference in the frequency and severity of attacks across BMI groups, although obese patients tended to have more attacks of high severity. There was no impact of BMI on the frequency of laryngeal attacks, but patients with normal BMI had fewer cutaneous attacks and more abdominal attacks. Most attacks (71.9-83.8%) were treated with a single icatibant injection without the need for rescue with plasma-derived C1-inhibitor (pdC1-INH), regardless of BMI. Patients with obese BMI used pdC1-INH as rescue treatment more often (P < 0.0001; P = 0.0232 excluding 2 outliers) and treated attacks earlier than patients with normal BMI (P = 0.007). Furthermore, time to resolution and duration of attack were shorter for patients with high BMI (P < 0.001 for overweight and P < 0.05 for obese versus normal). Overall, icatibant was comparatively effective in treating attacks in patients across all BMI groups. Trial registration NCT01034969.

Understanding Hereditary Angioedema

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American Academy of Allergy Asthma & Immunology Menu Search Main navigation Skip to content Conditions & Treatments Allergies Asthma Primary Immunodeficiency Disease Related Conditions Drug Guide Conditions Dictionary Just ...

Angioedema in heart failure patients treated with sacubitril/valsartan (LCZ696) or enalapril in the PARADIGM-HF study.

Science.gov (United States)

Shi, Victor; Senni, Michele; Streefkerk, Hendrik; Modgill, Vikas; Zhou, Wenchun; Kaplan, Allen

2018-08-01

PARADIGM-HF demonstrated significant clinical benefits for sacubitril/valsartan (LCZ696, an angiotensin receptor neprilysin inhibitor) versus the angiotensin-converting enzyme inhibitor (ACEI) enalapril in patients with heart failure with reduced ejection fraction. As inhibition of ACE, and co-inhibition of ACE and neprilysin, may increase the risk of angioedema, this was an adverse event of special interest. Following sequential enalapril and sacubitril/valsartan run-ins, patients were randomized to twice-daily sacubitril/valsartan 200 mg or enalapril 10 mg. The study design incorporated two wash-out periods (~36 h each) to minimize any potential risk of angioedema due to overlapping ACE and neprilysin inhibition. Suspected cases of angioedema were reported to, and blindly adjudicated by, an independent angioedema adjudication committee (AAC). Of the 10,513 patients entering the enalapril run-in, 9419 entered the sacubitril/valsartan run-in and 8432 received double-blind treatment. Overall, 148 suspected angioedema events occurring in 144 patients were reported to AAC, with one event reported during screening period. Of the remaining 147 events, 54 were confirmed as angioedema by AAC. A confirmed event was experienced by 15 (0.14%) and 10 (0.11%) patients, during the enalapril and sacubitril/valsartan run-ins, respectively, and by 10 (0.24%) and 19 (0.45%) patients in the corresponding randomized arms during the double-blind phase. The frequency of confirmed angioedema was higher in black patients. Most events were mild. Only five patients required hospitalization and none required mechanical airway support. The number of confirmed angioedema events in PARADIGM-HF was low and there was no-marked excess risk of angioedema with sacubitril/valsartan versus enalapril. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Rituximab therapy in a patient with low grade B-cell lymphoproliferative disease and concomitant acquired angioedema

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Kaur R

2014-12-01

Full Text Available Ravdeep Kaur, Aerik Anthony Williams, Catherine Baker Swift, Jason W Caldwell Wake Forest University School of Medicine, Wake Forest University, Winston-Salem, NC, USA Abstract: Acquired angioedema is often associated with significant morbidity. An underlying lymphatic malignancy, autoimmune disorder, adenocarcinoma, or other malignancy may be present. Screening for these disorders should occur in all patients with acquired angioedema as treatment may result in resolution of angioedema. Keywords: complement, C1-INH deficiency, ecallantide, hemopathy

ACE Inhibitor-Induced Angioedema of the Intestine: Case Report, Incidence, Pathophysiology, Diagnosis and Management

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Gavin Oudit

2001-01-01

Full Text Available A case report of fosinopril-induced angioedema of the intestine with a chronic course accompanied by multiple acute exacerbations is described. Angiotensin-converting enzyme (ACE inhibitor-induced angioedema of the intestine (AIAI occurs in a minority of patients taking an ACE inhibitor. The clinical presentation encompasses acute abdominal symptoms, pronounced bowel edema and ascites with occasional facial and/or oropharyngeal swelling. AIAI is diagnosed based on the temporal relationship between the symptomatic presentation and drug use, absence of alternative diagnoses including other causes of angioedema, and the prompt resolution of symptoms upon discontinuation of the ACE inhibitor. Prompt radiological investigation (abdominal computerized tomography and/or ultrasound is critical in making an early diagnosis and in preventing unnecessary surgical intervention. There is a female predominance of AIAI, which may reflect the interaction of estradiol with the various pathways involved in the pathophysiology of AIAI. Management of AIAI consists mainly of conservative measures and discontinuation of the ACE inhibitor. Angiotensin II receptor antagonists should not be considered as appropriate alternatives. Awareness and knowledge of AIAI are important because of the increasing use of ACE inhibitors, current delays in making the diagnosis, obvious management strategies once the diagnosis is made and the dysutility of alternative diagnoses, which may lead to considerable morbidity. AIAI must be considered in patients taking ACE inhibitors who develop gastrointestinal complaints irrespective of the duration of the therapy.

Clinical characteristics and treatment of chronic urticaria and angioedema : Dwelling on swelling, dealing with whealing

NARCIS (Netherlands)

van den Elzen, M.T.

2017-01-01

The occurrence of wheals, angioedema or both for at least 6 weeks is diagnosed as chronic spontaneous urticaria in (inter) national guidelines - after excluding other illnesses. The underlying mechanism of angioedema without wheals is not entirely known. The objective of this thesis is to increase

Disease: H01799 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available H01799 Vibratory urticaria; Vibratory angioedema Vibratory urticaria is a rare typ...e of physical skin reactivity characterized by the occurrence of local erythematous, edematous, cutaneous an...enship ML, Pruzansky JJ ... TITLE ... Vibratory angioedema: a hereditary type of ph

Anaphylaxis due to head injury.

Science.gov (United States)

Bruner, Heather C; Bruner, David I

2015-05-01

Both anaphylaxis and head injury are often seen in the emergency department, but they are rarely seen in combination. We present a case of a 30-year-old woman who presented with anaphylaxis with urticaria and angioedema following a minor head injury. The patient responded well to intramuscular epinephrine without further complications or airway compromise. Prior case reports have reported angioedema from hereditary angioedema during dental procedures and maxillofacial surgery, but there have not been any cases of first-time angioedema or anaphylaxis due to head injury.

Hereditary Hearing Loss.

Science.gov (United States)

Tran, LenhAnh P.; Grundfast, Kenneth M.

1997-01-01

This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

Allergic contact dermatitis mimicking angioedema due to paraphenylendiamine hypersensitivity: a case report.

Science.gov (United States)

Tukenmez Demirci, Gulsen; Kivanc Altunay, Ilknur; Atis, Guldehan; Kucukunal, Asli

2012-09-01

Active sensitization to paraphenylendiamine (PPD) and related compounds from temporary black henna tattoos has become an epidemic in the recent years. Hair dyes also include PPD like black henna tatoos which cause allergic contact dermatitis. Skin lesions of allergic contact dermatitis from PPD are mostly seen as an exudative erythema, an erythema multiforme-like eruption or a bullous contact dermatitis. We, herein, report a 27 year-old woman with an angioedema-like reaction occurring after the first exposure to hair dye who was unaware of being previously sensitized to PPD from black henna tattoo.

Effect of omalizumab on angioedema in H1 -antihistamine-resistant chronic spontaneous urticaria patients: results from X-ACT, a randomized controlled trial.

Science.gov (United States)

Staubach, P; Metz, M; Chapman-Rothe, N; Sieder, C; Bräutigam, M; Canvin, J; Maurer, M

2016-08-01

Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied. The primary objective was to evaluate the efficacy of omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU-Q2oL) questionnaire. Number of angioedema-burdened days, time interval between successive angioedema episodes, disease activity, angioedema-specific and overall QoL impairment were secondary objectives. X-ACT was a phase III, randomized, double-blind study conducted in 24 centres (Germany), which selectively included CSU patients with angioedema and wheals. Patients were randomized (1 : 1) to omalizumab 300 mg or placebo (every 4 weeks up to week 24) (ClinicalTrials.gov number: NCT01723072). Of the 91 patients randomized to omalizumab (n = 44) or placebo (n = 47) at baseline, 68 completed the 28-week treatment phase (omalizumab, 35; placebo, 33). Omalizumab was superior to placebo in improving CU-Q2oL scores at week 28 (P omalizumab (0.3) vs placebo (1.1). The median time to first recurrence of angioedema was 57-63 days with omalizumab and Omalizumab significantly improved angioedema-specific QoL (P omalizumab. Omalizumab was an effective treatment option for patients with moderate-to-severe CSU symptoms and angioedema unresponsive to high doses of antihistamine treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

BRCA1/2 associated hereditary breast cancer

Institute of Scientific and Technical Information of China (English)

Li-song TENG; Yi ZHENG; Hao-hao WANG

2008-01-01

Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCA1 and/or BRCA2 genes. In this review, we provide an overview of these two genes,focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial;further studies are needed to elucidate the nature of BRCA1/2 associated hereditary breast cancers.

Acetyl salicylic acid induced-urticaria and/or angioedema in atopic children.

Science.gov (United States)

Botey, J; Navarro, C; Aulesa, C; Marín, A; Eseverri, J L

1988-01-01

From the report of Hirschberg, only 3 years after aspirin synthesis, there have been numerous works dedicated to showing the different types of adverse reactions found following aspirin administration. However, there are few publications on the process of urticaria and/or acute angioedema induced by ASA and few reported cases were found in children. Thus, we present 6 atopic children with urticaria and/or angioedema related with ASA. A carefully detailed history, oral provocation with ASA, oral provocation with other NSAI and HBDT with ASA were done to all of them. The oral provocation with ASA was positive in 5 of the 6 cases. The provocations with the rest of the NSAI and tartrazine and sodium benzoate were negative in all of the patients. The HBDT was positive in 5 of the cases. In conclusion, we insist that aspirin intolerance is not infrequent in infancy and it is not rare to see urticaria and or angioedema, in spite of the fact that asthmatics, atopics or non atopics, usually present as bronchospasm. We also believe that the HBDT can be a method of diagnosis used in these cases.

[Tranexamic acid as first-line emergency treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors].

Science.gov (United States)

Beauchêne, C; Martins-Héricher, J; Denis, D; Martin, L; Maillard, H

2018-05-04

Episodes of acquired bradykinin-mediated angioedema due to angiotensin-converting enzyme (ACE) inhibitors may result in fatal outcomes. There is no consensus regarding emergency pharmacological management of these episodes. Treatment options include icatibant and C1INH concentrate. Tranexamic acid is administered for moderate episodes. Its efficacy in the treatment of ACE inhibitor-induced episodes of angioedema is not established. The aim of this retrospective study is to assess the benefits of emergency tranexamic acid administration in the management of ACE inhibitor-induced episodes of angioedema. Retrospective analysis of the medical files of patients who consulted between 2010 and 2016 in two French tertiary care hospitals for a bradykinic angioedema attributed to an ACE treatment. All of them had received tranexamic acid as a first line treatment. Thirty three patients who had experienced severe episode of angioedema were included. Twenty seven patients showed significant improvement when treated with tranexamic acid alone. The six remaining patients were treated with icatibant (5/33) or C1INH concentrate (1/33), due to partial improvement after tranexamic acid therapy. None of the patients were intubated, no fatalities were recorded and no side effects were reported. Tranexamic acid is an easily accessible and affordable therapy that may provide effective treatment for ACE inhibitor-induced episodes of angioedema. It may help while waiting for a more specific treatment (icatibant and C1INH concentrate) that is at times unavailable in emergency departments. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Anaphylaxis Due to Head Injury

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Bruner, Heather C.

2015-05-01

Full Text Available Both anaphylaxis and head injury are often seen in the emergency department, but they are rarely seen in combination. We present a case of a 30-year-old woman who presented with anaphylaxis with urticaria and angioedema following a minor head injury. The patient responded well to intramuscular epinephrine without further complications or airway compromise. Prior case reports have reported angioedema from hereditary angioedema during dental procedures and maxillofacial surgery, but there have not been any cases of first-time angioedema or anaphylaxis due to head injury. [West J Emerg Med. 2015;16(3:435–437.

Dipeptidyl peptidase-4 inhibitor induced angioedema - an overlooked and potentially lethal adverse drug reaction?

DEFF Research Database (Denmark)

Scott, Susanne Irene; Andersen, Michelle Fog; Aagaard, Lise

2018-01-01

to vasodilatation and increase in vascular permeability in the capillaries. Objective To assess the risk and pathomechanism of angioedema due to inhibition of dipeptidyl peptidase-4 inhibitors when used as monotherapy and in combination with angiotensin converting enzyme-inhibitors. Method PubMed, Embase......, the Cochrane Library, PubMed Central, Web of Science, Google Scholar and clinicaltrials.gov were searched using different combinations of keywords "angioedema", "dipeptidyl peptidase 4", "dipeptidyl peptidase 4 inhibitors", "gliptins", "bradykinin", "substance P" and "angiotensin converting enzyme...

Fatal angioedema induced by angiotensin conversion enzyme (ACE ...

African Journals Online (AJOL)

ACE inhibitors are often prescribed in the treatment of hypertension, heart failure and kidney disease. These drugs are on the Essential Drugs List, and are therefore used at primary to tertiary health care levels in South Africa. Angioedema is considered a rare, but potentially fatal side-effect of this agent, with a reported ...

The molecular classification of hereditary endocrine diseases.

Science.gov (United States)

Ye, Lei; Ning, Guang

2015-12-01

Hereditary endocrine diseases are an important group of diseases with great heterogeneity. The current classification for hereditary endocrine disease is mostly based upon anatomy, which is helpful for pathophysiological interpretation, but does not address the pathogenic variability associated with different underlying genetic causes. Identification of an endocrinopathy-associated genetic alteration provides evidence for differential diagnosis, discovery of non-classical disease, and the potential for earlier diagnosis and targeted therapy. Molecular diagnosis should be routinely applied when managing patients with suspicion of hereditary disease. To enhance the accurate diagnosis and treatment of patients with hereditary endocrine diseases, we propose categorization of endocrine diseases into three groups based upon the function of the mutant gene: cell differentiation, hormone synthesis and action, and tumorigenesis. Each category was further grouped according to the specific gene function. We believe that this format would facilitate practice of precision medicine in the field of hereditary endocrine diseases.

Autoimmune thyroid disease as a risk factor for angioedema in patients with chronic idiopathic urticaria: a case-control study

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Ruy Felippe Brito Gonçalves Missaka

Full Text Available CONTEXT AND OBJECTIVE: An association between chronic idiopathic urticaria (CIU and autoimmune thyroid disease (ATD has been reported. However, there have not been any reports on whether ATD raises the risk of angioedema, which is a more severe clinical presentation of CIU. Thus, the aim of the present study was to evaluate whether the risk of angioedema is increased in patients with CIU and ATD. DESIGN AND SETTING: Case-control study including 115 patients with CIU at a tertiary public institution. METHODS: The patients were evaluated with regard to occurrence of angioedema and presence of ATD, hypothyroidism or hyperthyroidism. RESULTS: Angioedema was detected in 70 patients (60.9%. There were 22 cases (19.1% of ATD, 19 (16.5% of hypothyroidism and nine (7.8% of hyperthyroidism. The risk among patients with ATD was 16.2 times greater than among those without this thyroid abnormality (confidence interval, CI = 2.07-126.86. The odds ratio for hypothyroidism was 4.6 (CI = 1.00-21.54 and, for hyperthyroidism, 3.3 (CI = 0.38-28.36. CONCLUSIONS: Patients with CIU and ATD presented greater risk of angioedema, which reinforces the idea that a relationship exists between this allergic condition and thyroid autoimmunity. This finding could imply that such patients require specifically directed therapy.

Approaches to the diagnosis and management of patients with a history of nonsteroidal anti-inflammatory drug-related urticaria and angioedema.

Science.gov (United States)

Kowalski, Marek L; Woessner, Katharine; Sanak, Marek

2015-08-01

Nonsteroidal anti-inflammatory drug (NSAID)-induced urticarial and angioedema reactions are among the most commonly encountered drug hypersensitivity reactions in clinical practice. Three major clinical phenotypes of NSAID-induced acute skin reactions manifesting with angioedema, urticaria, or both have been distinguished: NSAID-exacerbated cutaneous disease, nonsteroidal anti-inflammatory drug-induced urticaria/angioedema (NIUA), and single NSAID-induced urticaria and angioedema. In some patients clinical history alone might be sufficient to establish the diagnosis of a specific type of NSAID hypersensitivity, whereas in other cases oral provocation challenges are necessary to confirm the diagnosis. Moreover, classification of the type of cutaneous reaction is critical for proper management. For example, in patients with single NSAID-induced reactions, chemically nonrelated COX-1 inhibitors can be safely used. However, there is cross-reactivity between the NSAIDs in patients with NSAID-exacerbated cutaneous disease and NIUA, and thus only use of selective COX-2 inhibitors can replace the culprit drug if the chronic treatment is necessary, although aspirin desensitization will allow for chronic treatment with NSAIDs in some patients with NIUA. In this review we present a practical clinical approach to the patient with NSAID-induced urticaria and angioedema. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

a case report of suspected angioedema in a child after ...

African Journals Online (AJOL)

consecutive days.16 Common side effects include: nausea, vomiting while rare side effects include: rash, alopecia, urticaria and angioedema. Adverse effects appear to occur more frequently when higher doses are used.17. A compiled information from Food and Drug administration (FDA) and Facts Med users submissions.

Hereditary periodic fever syndromes

NARCIS (Netherlands)

McDermott, MF; Frenkel, J

Hereditary periodic fever syndromes are defined by recurrent attacks of generalised inflammation for which no infectious or auto-immune cause can be identified. For most of these disorders, the molecular basis has recently been elucidated. This has opened the prospect of novel therapeutic

New treatments of hereditary blindness

DEFF Research Database (Denmark)

Bertelsen, Mette; Rosenberg, Thomas; Larsen, Michael

2013-01-01

Ongoing clinical trials are targeting several previously intractable hereditary causes of blindness of congenital, childhood or early adulthood onset, mainly in the optic nerve and retina. The intended stage of initiation of the new therapeutic approaches ranges from neonatal life and a structura......Ongoing clinical trials are targeting several previously intractable hereditary causes of blindness of congenital, childhood or early adulthood onset, mainly in the optic nerve and retina. The intended stage of initiation of the new therapeutic approaches ranges from neonatal life...... and a structurally intact retinal tissue to adult life with a complete loss of photoreceptors. It must be assumed that some of the trials will succeed in producing new therapies and action must be taken to refine and accelerate diagnostics and to preserve therapeutic potential in blind people....

Socioeconomic burden of hereditary angioedema

DEFF Research Database (Denmark)

Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen

2014-01-01

who were working or in school (n = 120), 72 provided work/school absenteeism data, resulting in an estimated 20 days missing from work/school on average per year; 51% (n = 84) indicated that HAE has hindered their career/educational advancement. CONCLUSION: HAE poses a considerable burden on patients...... and their families in terms of direct medical costs and indirect costs related to lost productivity. This burden is substantial at the time of attacks and in between attacks....

Hereditary Diffuse Gastric Cancer

Science.gov (United States)

... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 10/2017 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is a rare ...

Refractory Abdominal Pain in a Patient with Chronic Lymphocytic Leukemia: Be Wary of Acquired Angioedema due to C1 Esterase Inhibitor Deficiency

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Abdullateef Abdulkareem

2018-01-01

Full Text Available Acquired angioedema due to C1 inhibitor deficiency (C1INH-AAE is a rare and potentially fatal syndrome of bradykinin-mediated angioedema characterized by episodes of angioedema without urticaria. It typically manifests with nonpitting edema of the skin and edema in the gastrointestinal (GI tract mucosa or upper airway. Edema of the upper airway and tongue may lead to life-threatening asphyxiation. C1INH-AAE is typically under-diagnosed because of its rarity and its propensity to mimic more common abdominal conditions and allergic reactions. In this article, we present the case of a 62-year-old male with a history of recently diagnosed chronic lymphocytic leukemia (CLL who presented to our hospital with recurrent abdominal pain, initially suspected to have Clostridium difficile colitis and diverticulitis. He received a final diagnosis of acquired angioedema due to C1 esterase inhibitor deficiency due to concomitant symptoms of lip swelling, cutaneous nonpitting edema of his lower extremities, and complement level deficiencies. He received acute treatment with C1 esterase replacement and icatibant and was maintained on C1 esterase infusions. He also underwent chemotherapy for his underlying CLL and did not experience further recurrence of his angioedema.

Mutations in the nervous system--specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II.

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Shekarabi, Masoud; Girard, Nathalie; Rivière, Jean-Baptiste; Dion, Patrick; Houle, Martin; Toulouse, André; Lafrenière, Ronald G; Vercauteren, Freya; Hince, Pascale; Laganiere, Janet; Rochefort, Daniel; Faivre, Laurence; Samuels, Mark; Rouleau, Guy A

2008-07-01

Hereditary sensory and autonomic neuropathy type II (HSANII) is an early-onset autosomal recessive disorder characterized by loss of perception to pain, touch, and heat due to a loss of peripheral sensory nerves. Mutations in hereditary sensory neuropathy type II (HSN2), a single-exon ORF originally identified in affected families in Quebec and Newfoundland, Canada, were found to cause HSANII. We report here that HSN2 is a nervous system-specific exon of the with-no-lysine(K)-1 (WNK1) gene. WNK1 mutations have previously been reported to cause pseudohypoaldosteronism type II but have not been studied in the nervous system. Given the high degree of conservation of WNK1 between mice and humans, we characterized the structure and expression patterns of this isoform in mice. Immunodetections indicated that this Wnk1/Hsn2 isoform was expressed in sensory components of the peripheral nervous system and CNS associated with relaying sensory and nociceptive signals, including satellite cells, Schwann cells, and sensory neurons. We also demonstrate that the novel protein product of Wnk1/Hsn2 was more abundant in sensory neurons than motor neurons. The characteristics of WNK1/HSN2 point to a possible role for this gene in the peripheral sensory perception deficits characterizing HSANII.

Mutations in the nervous system–specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II

Science.gov (United States)

Shekarabi, Masoud; Girard, Nathalie; Rivière, Jean-Baptiste; Dion, Patrick; Houle, Martin; Toulouse, André; Lafrenière, Ronald G.; Vercauteren, Freya; Hince, Pascale; Laganiere, Janet; Rochefort, Daniel; Faivre, Laurence; Samuels, Mark; Rouleau, Guy A.

2008-01-01

Hereditary sensory and autonomic neuropathy type II (HSANII) is an early-onset autosomal recessive disorder characterized by loss of perception to pain, touch, and heat due to a loss of peripheral sensory nerves. Mutations in hereditary sensory neuropathy type II (HSN2), a single-exon ORF originally identified in affected families in Quebec and Newfoundland, Canada, were found to cause HSANII. We report here that HSN2 is a nervous system–specific exon of the with-no-lysine(K)–1 (WNK1) gene. WNK1 mutations have previously been reported to cause pseudohypoaldosteronism type II but have not been studied in the nervous system. Given the high degree of conservation of WNK1 between mice and humans, we characterized the structure and expression patterns of this isoform in mice. Immunodetections indicated that this Wnk1/Hsn2 isoform was expressed in sensory components of the peripheral nervous system and CNS associated with relaying sensory and nociceptive signals, including satellite cells, Schwann cells, and sensory neurons. We also demonstrate that the novel protein product of Wnk1/Hsn2 was more abundant in sensory neurons than motor neurons. The characteristics of WNK1/HSN2 point to a possible role for this gene in the peripheral sensory perception deficits characterizing HSANII. PMID:18521183

Partial Gene Deletions of PMP22 Causing Hereditary Neuropathy with Liability to Pressure Palsies

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Sun-Mi Cho

2014-01-01

Full Text Available Hereditary neuropathy with liability to pressure palsies (HNPP is an autosomal neuropathy that is commonly caused by a reciprocal 1.5 Mb deletion on chromosome 17p11.2, at the site of the peripheral myelin protein 22 (PMP22 gene. Other patients with similar phenotypes have been shown to harbor point mutations or small deletions, although there is some clinical variation across these patients. In this report, we describe a case of HNPP with copy number changes in exon or promoter regions of PMP22. Multiplex ligation-dependent probe analysis revealed an exon 1b deletion in the patient, who had been diagnosed with HNPP in the first decade of life using molecular analysis.

Facial Oedema Is Not Always Angioedema: A Case of Spontaneous Pneumomediastinum with Subcutaneous Emphysema during COPD Exacerbation

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Sarah Damanti

2015-10-01

Full Text Available We report a case of acute facial oedema in an elderly hospitalized patient which was initially misdiagnosed as angioedema secondary to antibiotics in a patient with an allergic diathesis. We describe the differential aetiologies and then the true cause of the oedema, which was an uncommon complication of a very common condition in the elderly: a pneumomediastinum with subcutaneous emphysema probably due to rupture of an emphysematous lung bulla during chronic obstructive pulmonary disease (COPD exacerbation. Lastly, we focus on the therapeutic procedures instituted for the treatment of the pneumomediastinum.

Hereditary Gigantism-the biblical giant Goliath and his brothers.

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Donnelly, Deirdre E; Morrison, Patrick J

2014-05-01

The biblical giant Goliath has an identifiable family tree suggestive of autosomal dominant inheritance. We suggest that he had a hereditary pituitary disorder possibly due to the AIP gene, causing early onset and familial acromegaly or gigantism. We comment on the evidence within the scriptures for his other relatives including a relative with six digits and speculate on possible causes of the six digits. Recognition of a hereditary pituitary disorder in the biblical Goliath and his family sheds additional information on his and other family members' battles with David and his relatives.

Isolated angioedema of the bowel due to C1 esterase inhibitor deficiency: a case report and review of literature

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Kothari Shivangi T

2011-02-01

Full Text Available Abstract Introduction We report a rare, classic case of isolated angioedema of the bowel due to C1-esterase inhibitor deficiency. It is a rare presentation and very few cases have been reported worldwide. Angioedema has been classified into three categories. Case presentation A 66-year-old Caucasian man presented with a ten-month history of episodic severe cramping abdominal pain, associated with loose stools. A colonoscopy performed during an acute attack revealed nonspecific colitis. Computed tomography of the abdomen performed at the same time showed a thickened small bowel and ascending colon with a moderate amount of free fluid in the abdomen. Levels of C4 ( Conclusion In addition to a detailed comprehensive medical history, laboratory data and imaging studies are required to confirm a diagnosis of angioedema due to C1 esterase inhibitor deficiency.

Pancreatic cancer risk in hereditary pancreatitis

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Frank Ulrich Weiss

2014-02-01

Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

[Paediatric retinal detachment and hereditary vitreoretinal disorders].

Science.gov (United States)

Meier, P

2013-09-01

The number of retinal detachments in children is very low in comparison to the number in adults. One predisposing factor for development of paediatric retinal detachment is suffering from hereditary vitreoretinal degeneration (e.g., Stickler syndrome, Wagner syndrome, Kniest dysplasia, familial exudative vitreoretinopathy, congenital X-linked retinoschisis, Knobloch syndrome, incontinentia pigmenti, Norrie disease). Hereditary vitreoretinopathies are characterised by an abnormal-appearing vitreous gel with associated retinal changes. In most of these eyes further ocular abnormalities can be diagnosed. A group of hereditary disorders is associated with characteristic systemic abnormalities. Allied conditions should be considered in the clinical diagnosis. Vitreoretinopathies are the most common cause of inherited retinal detachment. In most eyes primary vitrectomy is necessary, and disease-specific surgical treatment is discussed. Georg Thieme Verlag KG Stuttgart · New York.

Gene : CBRC-OANA-01-1559 [SEVENS

Lifescience Database Archive (English)

Full Text Available |Oan#S38831641 PREDICTED: Ornithorhynchus anatinus similar to serpin peptidase inhibitor, clade G (C1 inhibitor), member 1, (angioede...ma, hereditary), (LOC100079402), partial mRNA /cds=p(1,9

Gene : CBRC-OANA-01-0477 [SEVENS

Lifescience Database Archive (English)

Full Text Available |Oan#S38831641 PREDICTED: Ornithorhynchus anatinus similar to serpin peptidase inhibitor, clade G (C1 inhibitor), member 1, (angioede...ma, hereditary), (LOC100079402), partial mRNA /cds=p(1,9

Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention.

Science.gov (United States)

Sereno, María; Aguayo, Cristina; Guillén Ponce, Carmen; Gómez-Raposo, César; Zambrana, Francisco; Gómez-López, Miriam; Casado, Enrique

2011-09-01

Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes.

Immunophenotyping of hereditary breast cancer

NARCIS (Netherlands)

van der Groep, P.

2009-01-01

Hereditary breast cancer runs in families where several family members in different generations are affected. Most of these breast cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 which account for about 5% of all breast cancers. However, mutations in BRCA1 and BRCA2 may

Hereditary Lymphedema of the Leg – A Case Report

Directory of Open Access Journals (Sweden)

Birgit Heinig

2017-07-01

Full Text Available Primary of hereditary lymphedema is a rare but progressive disease. It is yet not curable. We present a 48-year-old male patient with hereditary lymphedema of his left leg, that was realised by minor trauma (able twist when he was seven years old. He had never been treated for lymphedema but experienced multiple erysipelas during his life. After diagnostic procedures to exclude other causes of leg swelling, the diagnosis of hereditary lymphedema of the leg, stage III was confirmed. We initialized complex decongestive therapy. During two weeks of intensive treatment, the circumference of the left leg could be reduced by 10 cm. This case illustrates the "natural course" hereditary lymphedema. But it raises the hope that even after decades of ignorance, the patients benefits from complex decongestive treatment. Therapeutic nihilism is unnecessary and poses lymphedema patients to risks of infection and secondary malignancies like Stewart-Trewes syndrome.

Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families.

NARCIS (Netherlands)

Vos tot Nederveen Cappel, W.H. de; Nagengast, F.M.; Griffioen, G.; Menko, F.H.; Taal, B.G.; Kleibeuker, J.H.; Vasen, H.F.

2002-01-01

PURPOSE: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive

Surveillance for hereditary nonpolyposis colorectal cancer - A long-term study on 114 families

NARCIS (Netherlands)

Cappel, WHDTN; Nagengast, FM; Griffioen, G; Menko, FH; Taal, BG; Kleibeuker, JH; Vasen, HF

2002-01-01

PURPOSE: Hereditary nonpolyposis colorectal cancer is caused by germline mutations in DNA mismatch repair genes. Mutation carriers have a 60 to 85 percent risk of developing colorectal cancer. In the Netherlands hereditary nonpolyposis colorectal cancer families are monitored in an intensive

Hereditary hemorrhagic telangiectasia clinical and molecular genetics

NARCIS (Netherlands)

Letteboer, T.G.W.

2010-01-01

Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber (ROW) syndrome is an autosomal dominant disease characterized by vascular malformations in multiple organ systems. HHT has an age-related penetrance and variable clinical expression. The clinical symptoms are caused by direct

Burden of Illness in Hereditary Angioedema

DEFF Research Database (Denmark)

Bygum, Anette; Aygören-Pürsün, Emel; Beusterien, Kathleen

2015-01-01

of HAE on health-related quality of life (HRQoL): (i) unnecessary treatments and procedures, (ii) symptom triggers, (iii) attack impacts, (iv) caregiver impacts, and (v) long-term impacts. Patients for example experienced unnecessary medical procedures due to diagnostic delays, anxiety and fear about...... attacks, and passing HAE to children, reduced work/school productivity, and limited career/educational achievement. Patient caregivers also experienced worry and work/activity interruption during the attacks. In conclusion, a conceptual model was developed illustrating the hypothesized relationships among...

The humanistic burden of hereditary angioedema

DEFF Research Database (Denmark)

Caballero, Teresa; Aygören-Pürsün, Emel; Bygum, Anette

2014-01-01

and impact of HAE types I and II from the patient perspective. The HAE Burden of Illness Study in Europe was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective via a one-time survey, which included items on clinical characteristics and physical......, traveling, and passing HAE to their children. Based on Hospital Anxiety and Depression Scale scores, 38 and 14% had clinically meaningful anxiety and depression, respectively. Despite standard of care, HAE patients still have frequent and painful attacks. Patients experience substantial impairment...

Genetics Home Reference: hereditary pancreatitis

Science.gov (United States)

... Facebook Twitter Home Health Conditions Hereditary pancreatitis Hereditary pancreatitis Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Hereditary pancreatitis is a genetic condition characterized by recurrent episodes ...

Hereditary breast cancer: from molecular pathology to tailored therapies.

Science.gov (United States)

Tan, D S P; Marchiò, C; Reis-Filho, J S

2008-10-01

Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.

Pes cavus and hereditary neuropathies: when a relationship should be suspected.

Science.gov (United States)

Piazza, S; Ricci, G; Caldarazzo Ienco, E; Carlesi, C; Volpi, L; Siciliano, G; Mancuso, M

2010-12-01

The hereditary peripheral neuropathies are a clinically and genetically heterogeneous group of diseases of the peripheral nervous system. Foot deformities, including the common pes cavus, but also hammer toes and twisting of the ankle, are frequently present in patients with hereditary peripheral neuropathy, and often represent one of the first signs of the disease. Pes cavus in hereditary peripheral neuropathies is caused by imbalance between the intrinsic muscles of the foot and the muscles of the leg. Accurate clinical evaluation in patients with pes cavus is necessary to exclude or confirm the presence of peripheral neuropathy. Hereditary peripheral neuropathies should be suspected in those cases with bilateral foot deformities, in the presence of family history for pes cavus and/or gait impairment, and in the presence of neurological symptoms or signs, such as distal muscle hypotrophy of limbs. Herein, we review the hereditary peripheral neuropathies in which pes cavus plays a key role as a "spy sign," discussing the clinical and molecular features of these disorders to highlight the importance of pes cavus as a helpful clinical sign in these rare diseases.

Hereditary myopathies with early respiratory insufficiency in adults.

Science.gov (United States)

Naddaf, Elie; Milone, Margherita

2017-11-01

Hereditary myopathies with early respiratory insufficiency as a predominant feature of the clinical phenotype are uncommon and underestimated in adults. We reviewed the clinical and laboratory data of patients with hereditary myopathies who demonstrated early respiratory insufficiency before the need for ambulatory assistance. Only patients with disease-causing mutations or a specific histopathological diagnosis were included. Patients with cardiomyopathy were excluded. We identified 22 patients; half had isolated respiratory symptoms at onset. The diagnosis of the myopathy was often delayed, resulting in delayed ventilatory support. The most common myopathies were adult-onset Pompe disease, myofibrillar myopathy, multi-minicore disease, and myotonic dystrophy type 1. Single cases of laminopathy, MELAS (mitochondrial encephalomyopathy with lactic acidosis and strokelike events), centronuclear myopathy, and cytoplasmic body myopathy were identified. We highlighted the most common hereditary myopathies associated with early respiratory insufficiency as the predominant clinical feature, and underscored the importance of a timely diagnosis for patient care. Muscle Nerve 56: 881-886, 2017. © 2017 Wiley Periodicals, Inc.

Availability of and access to orphan drugs: an international comparison of pharmaceutical treatments for pulmonary arterial hypertension, Fabry disease, hereditary angioedema and chronic myeloid leukaemia.

Science.gov (United States)

Blankart, Carl Rudolf; Stargardt, Tom; Schreyögg, Jonas

2011-01-01

Market authorization does not guarantee patient access to any given drug. This is particularly true for costly orphan drugs because access depends primarily on co-payments, reimbursement policies and prices. The objective of this article is to identify differences in the availability of orphan drugs and in patient access to them in 11 pharmaceutical markets: Australia, Canada, England, France, Germany, Hungary, the Netherlands, Poland, Slovakia, Switzerland and the US. Four rare diseases were selected for analysis: pulmonary arterial hypertension (PAH), Fabry disease (FD), hereditary angioedema (HAE) and chronic myeloid leukaemia (CML). Indicators for availability were defined as (i) the indications for which orphan drugs had been authorized in the treatment of these diseases; (ii) the application date; and (iii) the date upon which these drugs received market authorization in each country. Indicators of patient access were defined as (i) the outcomes of technology appraisals; (ii) the extent of coverage provided by healthcare payers; and (iii) the price of the drugs in each country. For PAH we analysed bosentan, iloprost, sildenafil, treprostinil (intravenous and inhaled) as well as sitaxentan and ambrisentan; for FD we analysed agalsidase alfa and agalsidase beta; for HAE we analysed icatibant, ecallantide and two complement C1s inhibitors; for CML we analysed imatinib, dasatinib and nilotinib. Most drugs included in this study had received market authorization in all countries, but the range of indications for which they had been authorized differed by country. The broadest range of indications was found in Australia, and the largest variations in indications were found for PAH drugs. Authorization process speed (the time between application and market authorization) was fastest in the US, with an average of 362 days, followed by the EU (394 days). The highest prices for the included drugs were found in Germany and the US, and the lowest in Canada, Australia and

[The progress and prospect of application of genetic testing technology-based gene detection technology in the diagnosis and treatment of hereditary cancer].

Science.gov (United States)

He, J X; Jiang, Y F

2017-08-06

Hereditary cancer is caused by specific pathogenic gene mutations. Early detection and early intervention are the most effective ways to prevent and control hereditary cancer. High-throughput sequencing based genetic testing technology (NGS) breaks through the restrictions of pedigree analysis, provide a convenient and efficient method to detect and diagnose hereditary cancer. Here, we introduce the mechanism of hereditary cancer, summarize, discuss and prospect the application of NGS and other genetic tests in the diagnosis of hereditary retinoblastoma, hereditary breast and ovarian cancer syndrome, hereditary colorectal cancer and other complex and rare hereditary tumors.

Genetics Home Reference: hereditary fructose intolerance

Science.gov (United States)

... Twitter Home Health Conditions Hereditary fructose intolerance Hereditary fructose intolerance Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Hereditary fructose intolerance is a condition that affects a person's ...

Hereditary and non-hereditary microangiopathies in the young. An up-date.

Science.gov (United States)

Ringelstein, E Bernd; Kleffner, Ilka; Dittrich, Ralf; Kuhlenbäumer, Gregor; Ritter, Martin A

2010-12-15

In recent years, a considerable number of new sporadic or hereditary small artery diseases of the brain have been detected which preferably occur in younger age, below 45 years. Cerebral microangiopathies constitute an appreciable portion of all strokes. In middle aged patients, hereditary cerebral small vessel diseases have to be separated from sporadic degenerative cerebral microangiopathy which is mainly due to a high vascular risk load. Features of the following disorders and details how to differentiate them, are reviewed here, namely CADASIL, MELAS, AD-RVLC, HEMID, CARASIL, PADMAL, FABRY, COL4A1-related cerebral small vessel diseases and a Portuguese type of autosomal dominant cerebral small vessel disease (SVDB). The symptomatic overlap of the cerebral microangiopathies include also other distinctive non-hereditary diseases like posterior (reversible) encephalopathy and Susac's syndrome which are also described. Some of the microangiopathies described here are not only seen in the young but also in the elderly. The precise diagnosis has direct therapeutic implications in several of these entities. Cerebral microangiopathies cause recurring strokes and diffuse white matter lesions leading to a broad spectrum of gait disturbances and in most of these disorders cognitive impairment or even vascular dementia in the long term. Often, they also involve the eye, the inner ear or the kidney. Several typical imaging findings from illustrative cases are presented. The order in which these diseases are presented here is not dictated by an inner logic principle, because a genetically or pathophysiologically based classification system of all these entities does not exist yet. Some entities are well established and not unusual, whereas others have only been described in a few cases in total. Copyright © 2010 Elsevier B.V. All rights reserved.

HAE international home therapy consensus document

DEFF Research Database (Denmark)

Longhurst, Hilary J; Farkas, Henriette; Craig, Timothy

2010-01-01

ABSTRACT: Hereditary angioedema (C1 inhibitor deficiency, HAE) is associated with intermittent swellings which are disabling and may be fatal. Effective treatments are available and these are most useful when given early in the course of the swelling. The requirement to attend a medical facility ...

Analysis of characteristics associated with reinjection of icatibant

DEFF Research Database (Denmark)

Longhurst, Hilary J; Aberer, Werner; Bouillet, Laurence

2015-01-01

PURPOSE: Phase 3 icatibant trials showed that most hereditary angioedema (HAE) (C1 inhibitor deficiency) acute attacks were treated successfully with one injection of icatibant, a selective bradykinin B2 receptor antagonist. We conducted a post hoc analysis of icatibant reinjection for HAE type I...

ELISA to measure neutralizing capacity of anti-C1-inhibitor antibodies in plasma of angioedema patients

NARCIS (Netherlands)

Engel, Ruchira; Rensink, Irma; Roem, Dorina; Brouwer, Mieke; Kalei, Asma; Perry, Dawn; Zeerleder, Sacha; Wouters, Diana; Hamann, Dörte

2015-01-01

Neutralizing autoantibodies (NAbs) against plasma serpin C1-inhibitor (C1-inh) are implicated in the rare disorder, acquired angioedema (AAE). There is insufficient understanding of the process of antibody formation and its correlation with disease progression and severity. We have developed an

A Case of Miller Fisher Syndrome, Thromboembolic Disease, and Angioedema: Association or Coincidence?

Science.gov (United States)

Salehi, Nooshin; Choi, Eric D; Garrison, Roger C

2017-01-16

BACKGROUND Miller Fisher Syndrome is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia, and is considered to be a variant of Guillain-Barre Syndrome. Miller Fisher Syndrome is observed in approximately 1-5% of all Guillain-Barre cases in Western countries. Patients with Miller Fisher Syndrome usually have good recovery without residual deficits. Venous thromboembolism is a common complication of Guillain-Barre Syndrome and has also been reported in Miller Fisher Syndrome, but it has generally been reported in the presence of at least one prothrombotic risk factor such as immobility. A direct correlation between venous thromboembolism and Miller Fisher Syndrome or Guillain-Barre Syndrome has not been previously described. CASE REPORT We report the case of a 32-year-old Hispanic male who presented with acute, severe thromboembolic disease and concurrently demonstrated characteristic clinical features of Miller Fisher Syndrome including ophthalmoplegia, ataxia, and areflexia. Past medical and family history were negative for thromboembolic disease, and subsequent hypercoagulability workup was unremarkable. During the course of hospitalization, the patient also developed angioedema. CONCLUSIONS We describe a possible association between Miller Fisher Syndrome, thromboembolic disease, and angioedema.

Aplastic crisis in occult hereditary spherocytosis caused by human parvovirus (HPV B19).

Science.gov (United States)

Rappaport, E S; Quick, G; Ransom, D; Helbert, B; Frankel, L S

1989-02-01

We have reported a case of aplastic crisis occurring in an 11-year-old black boy with occult hereditary spherocytosis. An etiologic diagnosis of human parvovirus (HPV) B19 infection was confirmed serologically. The Coulter Model S + IV proved useful for both diagnosis and treatment monitoring through serial histograms. The relationship of HPV infection and aplastic crisis is discussed.

Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

International Nuclear Information System (INIS)

Githu, Tangayi; Merrow, Arnold C.; Lee, Jason K.; Garrison, Aaron P.; Brown, Rebeccah L.

2014-01-01

Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

Energy Technology Data Exchange (ETDEWEB)

Githu, Tangayi [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Radiology of Huntsville, P.C., Huntsville, AL (United States); Merrow, Arnold C.; Lee, Jason K. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Garrison, Aaron P. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States); Akron Children' s Hospital, Pediatric Surgery, Akron, OH (United States); Brown, Rebeccah L. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States)

2014-03-15

Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

Hereditary chronic pancreatitis

Directory of Open Access Journals (Sweden)

Mössner Joachim

2007-01-01

Full Text Available Abstract Hereditary chronic pancreatitis (HCP is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2, the serine protease inhibitor, Kazal type 1 (SPINK1 and the cystic fibrosis transmembrane conductance regulator (CFTR have been found to be associated with chronic pancreatitis (idiopathic and hereditary as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.

HAE international home therapy consensus document

NARCIS (Netherlands)

Longhurst, Hilary J.; Farkas, Henriette; Craig, Timothy; Aygoren-Pursun, Emel; Bethune, Claire; Bjorkander, Janne; Bork, Konrad; Bouillet, Laurence; Boysen, Henrik; Bygum, Anette; Caballero, Teresa; Cicardi, Marco; Dempster, John; Gompels, Mark; Gooi, Jimmy; Grigoriadou, Sofia; Huffer, Ursula; Kreuz, Wolfhart; Levi, Marcel M.; Long, Janet; Martinez-Saguer, Inmaculada; Raguet, Michel; Reshef, Avner; Bowen, Tom; Zuraw, Bruce

2010-01-01

ABSTRACT: Hereditary angioedema (C1 inhibitor deficiency, HAE) is associated with intermittent swellings which are disabling and may be fatal. Effective treatments are available and these are most useful when given early in the course of the swelling. The requirement to attend a medical facility for

Hereditary pancreatitis for the endoscopist

OpenAIRE

Patel, Milan R.; Eppolito, Amanda L.; Willingham, Field F.

2013-01-01

Hereditary pancreatitis shares a majority of clinical and morphologic features with chronic alcoholic pancreatitis, but may present at an earlier age. The term hereditary pancreatitis has primarily been associated with mutations in the serine protease 1 gene (PRSS1) which encodes for cationic trypsinogen. PRSS1 mutations account for approximately 68–81% of hereditary pancreatitis. Mutations in other genes, primarily serine protease inhibitor Kazal type 1 (SPINK1) and the cystic fibrosis trans...

Hereditary chronic pancreatitis in a patient with type 1 diabetes mellitus

Directory of Open Access Journals (Sweden)

Varalakshmi Muthukrishnan

2018-01-01

Full Text Available In this case report, we present a young patient with type 1 diabetes who had hereditary chronic pancreatitis. We evaluated him for the cause of pancreatitis, but it was inconclusive and finally the genetic testing was done for him, which revealed heterozygous missense mutation in exon 3 of the PRSS1 gene (protease serine 1 gene on chromosome 7. Hence, we were able to make the diagnosis of hereditary chronic pancreatitis. Chronic pancreatitis secondary to any cause can lead to permanent diabetes, which is typically difficult to control. However, in this case, the episodes of recurrent pancreatitis were present after the onset of type 1 diabetes as compared to the usual presentation of diabetes after the advancement of chronic pancreatitis.

Transient angioedema of small bowel secondary to intravenous iodinated contrast medium

Directory of Open Access Journals (Sweden)

Kirankumar N Kulkarni

2014-01-01

Full Text Available We report the clinical details and imaging findings of a case of transient angioedema of the small bowel following intravenous administration of non-ionic iodinated contrast material in a 17 year old female with no predisposing risk factors. Findings included long segment, symmetric, circumferential, low-density, bowel wall thickening involving the duodenum, jejunum, and most of the ileum on computed tomography scan obtained at 7 min following intravenous contrast material injection. This entity is self-limiting with a favourable clinical outcome and requires no specific treatment but only aggressive clinical monitoring.

Leber's hereditary optic neuropathy and vitamin B12 deficiency

NARCIS (Netherlands)

Pott, Jan Willem R.; Wong, Kwok H.

2006-01-01

Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three

Determinants of angiotensin-converting enzyme inhibitor (ACEI) intolerance and angioedema in the UK Clinical Practice Research Datalink

NARCIS (Netherlands)

Mahmoudpour, Seyed Hamidreza; Baranova, Ekaterina Vitalievna; Souverein, Patrick C.; Asselbergs, Folkert W.; de Boer, Anthonius; Maitland-van der Zee, Anke Hilse

2016-01-01

AimThe aim of the present study was to describe the occurrence and determinants of angiotensin-converting enzyme (ACE) inhibitor (ACEI) intolerance and angioedema (AE) among patients initiating ACEI therapy in a real-world primary care population. MethodsTwo nested case-control studies were

Hereditary forms of breast cancer

International Nuclear Information System (INIS)

Bella, V.

2009-01-01

Breast cancer is the most common oncologic disease in the female population. Besides the sporadic occurrence it occurs in the familial and hereditary form. Persons with the occurrence of positive family anamnesis of breast cancer should be actively investigated. In the indicated cases it is necessary to send the woman to genetic examination. In case that the hereditary form of breast cancer is affirmed it is necessary to examine her family relatives. Women with the hereditary form of breast cancer occur in about 5 – 10 % portion from all women diagnosed with breast cancer. Nowadays we already know that 80 % of hereditary breast cancers are due to germ mutations in BRCA 1 and BRCA 2 gene. Persons with detected gene mutations must be dispensarized in the centres intended for it. (author)

Generation of patient-specific induced pluripotent stem cells from Leber's hereditary optic neuropathy

Directory of Open Access Journals (Sweden)

Huai-En Lu

2018-04-01

Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited mitochondrial disease caused by homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. In this report, we generated an induced pluripotent stem cell (iPSCs line, TVGH-iPSC-010-09, from the peripheral blood mononuclear cells of a female patient with Leber's hereditary optic neuropathy (LHON by using the Sendai-virus delivery system. The resulting iPSCs retained the disease-causing mitochondrial DNA mutation, expressed pluripotent markers and could differentiate into the three germ layers. We believe LHON patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease.

Whole-exome sequencing for diagnosis of hereditary ichthyosis.

Science.gov (United States)

Sitek, J C; Kulseth, M A; Rypdal, K B; Skodje, T; Sheng, Y; Retterstøl, L

2018-02-14

Hereditary ichthyosis constitutes a diverse group of cornification disorders. Identification of the molecular cause facilitates optimal patient care. We wanted to estimate the diagnostic yield of applying whole-exome sequencing (WES) in the routine genetic workup of inherited ichthyosis. During a 3-year-period, all ichthyosis patients, except X-linked and mild vulgar ichthyosis, consecutively admitted to a university hospital clinic were offered WES with subsequent analysis of ichthyosis-related genes as a first-line genetic investigation. Clinical and molecular data have been collected retrospectively. Genetic variants causative for the ichthyosis were identified in 27 of 34 investigated patients (79.4%). In all, 31 causative mutations across 13 genes were disclosed, including 12 novel variants. TGM1 was the most frequently mutated gene, accounting for 43.7% of patients suffering from autosomal recessive congenital ichthyosis (ARCI). Whole-exome sequencing appears an effective tool in disclosing the molecular cause of patients with hereditary ichthyosis seen in clinical practice and should be considered a first-tier genetic test in these patients. © 2018 European Academy of Dermatology and Venereology.

Hereditary Transthyretin Amyloidosis in Eight Chinese Families

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Ling-Chao Meng

2015-01-01

Full Text Available Background: Mutations of transthyretin (TTR cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis. Methods: Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed. Results: The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2. Conclusions: Since the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.

Hereditary pituitary hyperplasia with infantile gigantism.

Science.gov (United States)

Gläsker, Sven; Vortmeyer, Alexander O; Lafferty, Antony R A; Hofman, Paul L; Li, Jie; Weil, Robert J; Zhuang, Zhengping; Oldfield, Edward H

2011-12-01

We report hereditary pituitary hyperplasia. The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. The study is a retrospective analysis of three cases from one family. The study was conducted at the National Institutes of Health, a tertiary referral center. A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. The condition was treated by total hypophysectomy. We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.

Deprivation amblyopia and congenital hereditary cataract.

Science.gov (United States)

Mansouri, Behzad; Stacy, Rebecca C; Kruger, Joshua; Cestari, Dean M

2013-01-01

Amblyopia is a neurodevelopmental disorder of vision associated with decreased visual acuity, poor or absent stereopsis, and suppression of information from one eye.(1,2) Amblyopia may be caused by strabismus (strabismic amblyopia), refractive error (anisometropic amblyopia), or deprivation from obstructed vision (deprivation amblyopia). 1 In the developed world, amblyopia is the most common cause of childhood visual impairment, 3 which reduces quality of life 4 and also almost doubles the lifetime risk of legal blindness.(5, 6) Successful treatment of amblyopia greatly depends on early detection and treatment of predisposing disorders such as congenital cataract, which is the most common cause of deprivational amblyopia. Understanding the genetic causes of congenital cataract leads to more effective screening tests, early detection and treatment of infants and children who are at high risk for hereditary congenital cataract.

Pancreatic cancer risk in hereditary pancreatitis

OpenAIRE

Weiss, Frank U.

2014-01-01

Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1) gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic...

[Hereditary motor and sensory Lom-neuropathy--first Hungarian case report].

Science.gov (United States)

Szabó, Antal; Siska, Eva; Molnár, Mária Judit

2007-01-20

Hereditary motor and sensory neuropathy-Lom is an autosomal recessive disorder of the peripheral nervous system, which occurs only in the european Roma population. The symptoms start in the first decade with slowly progressive gait disturbance, weakness and wasting of distal upper extremity muscles, joint deformities and hearing loss develop later in the second and third decades. This disorder is caused by a homozygous missense mutation of the NDRG1 gene, located in the 8q24 region. The Schwann cell dysfunction is most probably caused by altered lipid metabolism as a consequence of the NDRG1 mutation. Molecular genetic testing can be a first diagnostic step among roma individuals showing a Lom neuropathy phenotype, making evaluation of such patients and also genetic counselling faster and easier. Screening for hereditary neuromuscular disorders in this genetically isolated community may become an important public health issue in the near future.

Blocking protein quality control to counter hereditary cancers

DEFF Research Database (Denmark)

Kampmeyer, Caroline; Nielsen, Sofie V.; Clausen, Lene

2017-01-01

cancer susceptibility syndromes, such as Lynch syndrome and von Hippel-Lindau disease, are caused by missense mutations in tumor suppressor genes, and in some cases, the resulting amino acid substitutions in the encoded proteins cause the cellular PQC system to target them for degradation, although...... by stabilizing with chemical chaperones, or by targeting molecular chaperones or the ubiquitin-proteasome system, may thus avert or delay the disease onset. Here, we review the potential of targeting the PQC system in hereditary cancer susceptibility syndromes....

Idiopathic Non-histaminergic Angioedema: Successful Treatment with Omalizumab in Five Patients.

Science.gov (United States)

Faisant, Charles; Du Thanh, Aurélie; Mansard, Catherine; Deroux, Alban; Boccon-Gibod, Isabelle; Bouillet, Laurence

2017-01-01

Idiopathic non-histaminergic acquired angioedema (InH-AAE) is a rare disease characterized by AE resistant to antihistamines and a chronic course. We report five new cases of InH-AAE (two women and three men) with a rapid and dramatic response to the anti-immunoglobulin-E antibody omalizumab. In our literature review, we found 13 other relevant cases with a good response to this treatment. Overall, in 6 out of 18 patients, the doses of omalizumab required to prevent recurrences of attacks were higher than the licensed dose for chronic urticaria. No significant adverse effects have been reported.

Startle responses in hereditary hyperekplexia

NARCIS (Netherlands)

Tijssen, M. A.; Voorkamp, L. M.; Padberg, G. W.; van Dijk, J. G.

1997-01-01

BACKGROUND: Patients with hereditary hyperekplexia have excessive startle responses that are accompanied by transient stiffness and also continuous stiffness in infancy. A point of mutation has been identified for the major form of hereditary hyperekplexia in the gene encoding the alpha 1 subunit of

Startle responses in hereditary hyperekplexia

NARCIS (Netherlands)

Tijssen, MAJ; Voorkamp, LM; Padberg, GW; vanDijk, JG

Background: Patients with hereditary hyperekplexia have excessive startle responses that are accompanied by transient stiffness and also continuous stiffness in infancy. A point of mutation has been identified for the major form of hereditary hyperekplexia in the gene encoding the alpha 1 subunit of

Could Ossification of the Achilles Tendon Have a Hereditary Component?

Directory of Open Access Journals (Sweden)

Chawki Cortbaoui

2013-01-01

Full Text Available Ossification of the Achilles tendon (OTA is an unusual clinical condition. It is characterized by the presence of an ossified mass within the fibrocartilaginous substance of the Achilles tendon. The etiology of the ossification of the Achilles tendon is unknown. Review of the literature suggests that its etiology is multifactorial. The major contributing factors are trauma and surgery with other minor causes such as systemic diseases, metabolic conditions, and infections. To our knowledge, no previous reports suggest any genetic/hereditary predisposition in OAT. We report 3 siblings who have OAT with no history of any of the aforementioned predisposing factors. Could OAT have a hereditary component as one of its etiologies?

Combined pulmonary involvement in hereditary lysozyme amyloidosis with associated pulmonary sarcoidosis: a case report.

Science.gov (United States)

McCarthy, Cormac; Deegan, Alexander P; Garvey, John F; McDonnell, Timothy J

2013-12-17

Sarcoidosis is a multisystem inflammatory disorder of unknown cause which can affect any organ system. Autosomal dominant lysozyme amyloidosis is a very rare form of hereditary amyloidosis. The Arg64 variant is extraordinarily rare with each family showing a particular pattern of organ involvement, however while Sicca syndrome, gastrointestinal involvement and renal failure are common, lymph node involvement is very rare. In this case report we describe the first reported case of sarcoidosis in association with hereditary lysozyme amyloidosis.

Cellular characteristics of hereditary diseases of man

International Nuclear Information System (INIS)

Sasaki, Masao

1978-01-01

Hereditary diseases of which abnormal characters could be detected at cultured cell level were introduced, and tissue cultures of them were described. Characteristics such as reproduction, disorder, elimination, and repair of DNA in hereditary diseases with high cancer risk such as Bloom syndrome, etc. were investigated. Radiosensitivity of these hereditary diseases was also described, and factors of carcinogenesis were investigated. (Serizawa, K.)

[Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is caused by a mutation in TFG].

Science.gov (United States)

Ishiura, Hiroyuki; Tsuji, Shoji

2013-01-01

Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an autosomal dominant neurodegenerative disease characterized by proximal predominant weakness and muscle atrophy accompanied by distal sensory disturbance. Linkage analysis using 4 families identified a region on chromosome 3 showing a LOD score exceeding 4. Further refinement of candidate region was performed by haplotype analysis using high-density SNP data, resulting in a minimum candidate region spanning 3.3 Mb. Exome analysis of an HMSN-P patient revealed a mutation (c.854C>T, p.Pro285Leu) in TRK-fused gene (TFG). The identical mutation was found in the four families, which cosegregated with the disease. The mutation was neither found in Japanese control subjects nor public databases. Detailed haplotype analysis suggested two independent origins of the mutation. These findings indicate that the mutation in TFG causes HMSN-P.

Hereditary haemorrhagic telangiectasia: a cause of preventable morbidity and mortality.

LENUS (Irish Health Repository)

Brady, A P

2012-01-31

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant condition whose effects are mediated through deficient blood vessel formation and regeneration, with multisystem involvement. Patients are usually aware of resulting skin telangiectasia and epistaxis, but are also exposed to dangers posed by occult vascular malformations in other organs. About 15-35% of HHT patients have pulmonary AVMs (PAVMs), 10% have cerebral AVMs (CAVMs), 25-33% suffer significant GI blood loss from GI tract telangiectasia, and an unknown but high percentage have liver involvement. In total, 10% of affected individuals die prematurely or suffer major disability from HHT, largely because of bleeding from CAVMs and PAVMs, or paradoxical embolization through PAVMs. Screening for and early intervention to treat occult PAVMs and CAVMs can largely eliminate these risks, and should be undertaken in a specialist centre. The National HHT Center in The Mercy University Hospital in Cork is the referral centre for HHT screening in Ireland.

Targeted high-throughput sequencing identifies mutations in atlastin-1 as a cause of hereditary sensory neuropathy type I.

Science.gov (United States)

Guelly, Christian; Zhu, Peng-Peng; Leonardis, Lea; Papić, Lea; Zidar, Janez; Schabhüttl, Maria; Strohmaier, Heimo; Weis, Joachim; Strom, Tim M; Baets, Jonathan; Willems, Jan; De Jonghe, Peter; Reilly, Mary M; Fröhlich, Eleonore; Hatz, Martina; Trajanoski, Slave; Pieber, Thomas R; Janecke, Andreas R; Blackstone, Craig; Auer-Grumbach, Michaela

2011-01-07

Hereditary sensory neuropathy type I (HSN I) is an axonal form of autosomal-dominant hereditary motor and sensory neuropathy distinguished by prominent sensory loss that leads to painless injuries. Unrecognized, these can result in delayed wound healing and osteomyelitis, necessitating distal amputations. To elucidate the genetic basis of an HSN I subtype in a family in which mutations in the few known HSN I genes had been excluded, we employed massive parallel exon sequencing of the 14.3 Mb disease interval on chromosome 14q. We detected a missense mutation (c.1065C>A, p.Asn355Lys) in atlastin-1 (ATL1), a gene that is known to be mutated in early-onset hereditary spastic paraplegia SPG3A and that encodes the large dynamin-related GTPase atlastin-1. The mutant protein exhibited reduced GTPase activity and prominently disrupted ER network morphology when expressed in COS7 cells, strongly supporting pathogenicity. An expanded screen in 115 additional HSN I patients identified two further dominant ATL1 mutations (c.196G>C [p.Glu66Gln] and c.976 delG [p.Val326TrpfsX8]). This study highlights an unexpected major role for atlastin-1 in the function of sensory neurons and identifies HSN I and SPG3A as allelic disorders.

The Variant p.(Arg183Trp) in SPTLC2 Causes Late-Onset Hereditary Sensory Neuropathy.

Science.gov (United States)

Suriyanarayanan, Saranya; Auranen, Mari; Toppila, Jussi; Paetau, Anders; Shcherbii, Maria; Palin, Eino; Wei, Yu; Lohioja, Tarja; Schlotter-Weigel, Beate; Schön, Ulrike; Abicht, Angela; Rautenstrauss, Bernd; Tyynismaa, Henna; Walter, Maggie C; Hornemann, Thorsten; Ylikallio, Emil

2016-03-01

Hereditary sensory and autonomic neuropathy 1 (HSAN1) is an autosomal dominant disorder that can be caused by variants in SPTLC1 or SPTLC2, encoding subunits of serine palmitoyl-CoA transferase. Disease variants alter the enzyme's substrate specificity and lead to accumulation of neurotoxic 1-deoxysphingolipids. We describe two families with autosomal dominant HSAN1C caused by a new variant in SPTLC2, c.547C>T, p.(Arg183Trp). The variant changed a conserved amino acid and was not found in public variant databases. All patients had a relatively mild progressive distal sensory impairment, with onset after age 50. Small fibers were affected early, leading to abnormalities on quantitative sensory testing. Sural biopsy revealed a severe chronic axonal neuropathy with subtotal loss of myelinated axons, relatively preserved number of non-myelinated fibers and no signs for regeneration. Skin biopsy with PGP9.5 labeling showed lack of intraepidermal nerve endings early in the disease. Motor manifestations developed later in the disease course, but there was no evidence of autonomic involvement. Patients had elevated serum 1-deoxysphingolipids, and the variant protein produced elevated amounts of 1-deoxysphingolipids in vitro, which proved the pathogenicity of the variant. Our results expand the genetic spectrum of HSAN1C and provide further detail about the clinical characteristics. Sequencing of SPTLC2 should be considered in all patients presenting with mild late-onset sensory-predominant small or large fiber neuropathy.

[Facial and oropharyngeal angioedema in patient with alimentary fish allergy. Diagnosis and treatment].

Science.gov (United States)

Pino Rivero, V; Rodríguez Carmona, M; Iglesias González, R J; del Castillo Beneyto, F

2007-01-01

Vegetal or animal food can produce hipersensibility reactions IgE mediated of diverse intensity. We report the case of a 54 years old woman without previous allergic antecedents who after eating frozen fish had to go to Emergencies due to angioedema especially in face and oropharynx. The ENT exploration by fibroscopia descarted laryngeal edema but the patient showed initially respiratory symptoms so she was treated with SC adrenalina and then steroids during her admission. The diagnosis of alimentary alergia would be confirmed after by Allergology with cutaneous test prick type.

Splenic Involvement in Hereditary Hemorrhagic Telangiectasia

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Susumu Takamatsu

2016-01-01

Full Text Available A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities.

Non-motor Symptoms In Patients With Hereditary Spastic Paraplegia Caused By Spg4 Mutations.

OpenAIRE

Servelhere, K R; Faber, I; Saute, J A M; Moscovich, M; D'Abreu, A; Jardim, L B; Teive, H A G; Lopes-Cendes, I; Franca, M C

2016-01-01

Non-motor manifestations are frequently overlooked in degenerative disorders and little is known about their frequency and clinical relevance in SPG4 hereditary spastic paraplegia (SPG4-HSP). Thirty patients with SPG4-HSP and 30 healthy controls answered the Modified Fatigue Impact Scale, Epworth Sleepiness Scale, Brief Pain Inventory and Beck Depression Inventory. Student's t test was used to compare groups and linear regression was used to assess correlations. Patients had higher fatigue sc...

The metabolomic signature of Leber's hereditary optic neuropathy reveals endoplasmic reticulum stress.

Science.gov (United States)

Chao de la Barca, Juan Manuel; Simard, Gilles; Amati-Bonneau, Patrizia; Safiedeen, Zainab; Prunier-Mirebeau, Delphine; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Gueguen, Naïg; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Ferré, Marc; Bris, Céline; Kouassi Nzoughet, Judith; Bocca, Cinzia; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Lenaers, Guy; Martinez, M Carmen; Procaccio, Vincent; Reynier, Pascal

2016-11-01

Leber's hereditary optic neuropathy (MIM#535000), the commonest mitochondrial DNA-related disease, is caused by mutations affecting mitochondrial complex I. The clinical expression of the disorder, usually occurring in young adults, is typically characterized by subacute, usually sequential, bilateral visual loss, resulting from the degeneration of retinal ganglion cells. As the precise action of mitochondrial DNA mutations on the overall cell metabolism in Leber's hereditary optic neuropathy is unknown, we investigated the metabolomic profile of the disease. High performance liquid chromatography coupled with tandem mass spectrometry was used to quantify 188 metabolites in fibroblasts from 16 patients with Leber's hereditary optic neuropathy and eight healthy control subjects. Latent variable-based statistical methods were used to identify discriminating metabolites. One hundred and twenty-four of the metabolites were considered to be accurately quantified. A supervised orthogonal partial least squares discriminant analysis model separating patients with Leber's hereditary optic neuropathy from control subjects showed good predictive capability (Q 2cumulated = 0.57). Thirty-eight metabolites appeared to be the most significant variables, defining a Leber's hereditary optic neuropathy metabolic signature that revealed decreased concentrations of all proteinogenic amino acids, spermidine, putrescine, isovaleryl-carnitine, propionyl-carnitine and five sphingomyelin species, together with increased concentrations of 10 phosphatidylcholine species. This signature was not reproduced by the inhibition of complex I with rotenone or piericidin A in control fibroblasts. The importance of sphingomyelins and phosphatidylcholines in the Leber's hereditary optic neuropathy signature, together with the decreased amino acid pool, suggested an involvement of the endoplasmic reticulum. This was confirmed by the significantly increased phosphorylation of PERK and eIF2α, as well as

Genetics Home Reference: hereditary hemorrhagic telangiectasia

Science.gov (United States)

... Central OMIM: JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic ... 10.1097/GIM.0b013e3182136d32. Review. Citation on PubMed McDonald J, Wooderchak-Donahue W, VanSant Webb C, Whitehead ...

A novel A792D mutation in the CSF1R gene causes hereditary diffuse leukoencephalopathy with axonal spheroids characterized by slow progression

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Sakiho Ueda

2015-03-01

Full Text Available Hereditary diffuse leukoencephalopathy with spheroids (HDLS is an autosomal dominant white matter disease that causes adult-onset cognitive impairment. The clinical manifestations are a variable combination of personality and behavioral changes, cognitive decline, parkinsonism, spasticity, and epilepsy. In 2012, mutations in the gene encoding colony stimulating factor 1 receptor (CSF1R were identified as the cause of HDLS. As the numbers of reported mutations are limited, the understanding of whole pathogenesis needs accumulation of disease-causing mutations with detailed clinical descriptions. We describe a Japanese family with autosomal dominant adult-onset cognitive impairment and characteristic white matter lesions. Genetic testing revealed a novel p.A792D mutation in the tyrosine kinase domain of CSF1R in two affected family members. The symptom profile of the present cases mostly matched the previously reported cases, with the notable exceptions of late-onset and long disease duration.

Pavlodar city children's some hereditary diseases

International Nuclear Information System (INIS)

Shajmardanova, B. Kh.; Gorbach, S.V.

1997-01-01

Territory of the Pavlodar region directly adjoining to the Semipalatinsk test site is unique object for study of many year tests consequences on population health. Health worsening caused by small doses of radiation on artificial pollution background is defined. Purpose of the work is Pavlodar city children's some hereditary diseases (Downs syndrome, crack of upper lip and/or palate, hemophilia) under study of frequency dynamic of statistical data within period from 1980 by 1995. It is defined: a) tendency to growth Downs syndrome frequency has been distinctly observed beginning of the 1982; b) it is noted Downs syndrome frequency growth stabilization within period from 1988 by 1991; c) among children with Downs syndrome is distinguished low viability; d) there is rather higher correlation rate of Downs syndrome and congenial heart threshold against average statistical index; e) character of frequencies changes of crack of upper lip and/or palate has tendency to growth; f) it is defined that boys predominate among children with this disease; g) congenial crack of soft palate have being revealed as solitary thresholds of development; h) genealogy analysis of hemophilia sick reveals, that it has only hereditary character. 8 refs

Hereditary neuropathies: systematization and diagnostics (clinical case of hereditary motor and sensor neuropathy of the IA type

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Kolokolova A.M.

2016-09-01

Full Text Available Aim: to study the value of routine methods (clinical symptoms, electrophysiological findings and results of DNA analysis in diagnostics of hereditary motor sensory neuropathy type IA in outpatient clinics. Material and Methods. The review of foreign literature is represented. The phenotypic polymorphism, genetic heterogeneity and the difficulties of diagnostics are identified. A family with hereditary motor sensory neuropathy of lAtype is presented, which was diagnosed on the base of available methods in outpatient practice (clinical symptoms, genealogical method, electro-physiological findings and DNA analysis results. Results. Routine algorithm (consistent valuation of clinical symptoms, neurophysiologic findings and the results of DNA analysis helped to verify the diagnosis of hereditary motor sensory neuropathy of lAtype in outpatient practice after more than 20 years of the onset of the disease. Conclusion. The neurologists of outpatient clinics and other specialists must be informed about the availability of diagnostics of hereditary diseases of nervous system.

Hereditary colorectal cancer diagnostics

DEFF Research Database (Denmark)

Klarskov, Louise; Holck, Susanne; Bernstein, Inge

2012-01-01

BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...

Chaperonopathies: spotlight on hereditary motor neuropathies

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Vincenzo Lupo

2016-12-01

Full Text Available Distal hereditary motor neuropathies (dHMN comprise a group of rare hereditary neuromuscular disorders characterized by a peroneal muscular atrophy without sensory symptoms. To date twenty-three genes for dHMN have been reported and four of them encode for chaperones: DNAJB2, which encodes a member of the HSP40/DNAJ co-chaperone family, and HSPB1, HSPB3 and HSPB8, which encode three members of the family of small heat shock proteins. Except for HSPB1, with around thirty different mutations, the remaining three genes comprise a much low number of cases. Thus, only one case has been described caused by an HSPB3 mutation, whereas few DNAJB2 and HSPB8 cases are known, most of them caused by a founder c.352+1G>A mutation in DNAJB2 and by mutations affecting the hot spot K141 residue of the HSPB8 chaperone. This low number of cases makes it difficult to understand the pathomechanism underlying the neuropathy. Chaperones can assemble in multi-chaperone complexes forming an integrative chaperone network in the cell, which plays relevant cellular roles in a variety of processes such as the correct folding of newly synthesized proteins, their escort to their precise cellular locations to form functional proteins and complexes and the response to protein misfolding, including the degradation of proteins that fail to refold properly. Despite of this variety of functions, mutations in some of them lead to diseases with a similar clinical picture, suggesting common pathways. This review gives an overview of the genetics of dHMNs caused by mutations in four genes, DNAJB2, HSPB1, HSPB3 and HSPB8, which encode chaperones and show a common disease mechanism.

Hereditary vacuolar internal anal sphincter myopathy causing proctalgia fugax and constipation: a new case contribution.

Science.gov (United States)

de la Portilla, Fernando; Borrero, Juan José; Rafel, Enrique

2005-03-01

Hereditary anal sphincter myopathy is rare. We present a family with one affected member with proctalgia fugax, constipation and internal anal sphincter hypertrophy. Ultrastructural findings show vacuolization of smooth muscle cells without the characteristic polyglucosan inclusion. Further relief of symptoms was obtained using an oral calcium antagonist. Based on clinical presentation, endosonography and morphological findings, we consider our case is a histological variant of the vacuolar myopathy originally described.

Genetics Home Reference: hereditary diffuse gastric cancer

Science.gov (United States)

... Health Conditions Hereditary diffuse gastric cancer Hereditary diffuse gastric cancer Printable PDF Open All Close All Enable Javascript ... Diffuse Gastric Cancer MedlinePlus Encyclopedia: Gastric Cancer National Cancer ... Option Overview General Information from MedlinePlus ( ...

Drug therapy for hereditary cancers

Directory of Open Access Journals (Sweden)

Imyanitov Evgeny N

2011-08-01

Full Text Available Abstract Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose polymerase (PARP. Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC. Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC patients; studies involving non-selected (i.e., both sporadic and hereditary CRC with high-level microsatellite instability (MSI-H suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP. Hereditary medullary thyroid cancers (MTC have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies.

Genetic profiles distinguish different types of hereditary ovarian cancer

DEFF Research Database (Denmark)

Domanska, Katarina; Malander, Susanne; Staaf, Johan

2010-01-01

(HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers......Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....

Benefits and risks of danazol in hereditary angioedema

DEFF Research Database (Denmark)

Bork, Konrad; Bygum, Anette; Hardt, Jochen

2008-01-01

the benefits and risks of long-term treatment with danazol. METHODS: Data were generated retrospectively from 118 German and Danish patients who had HAE due to C1 inhibitor deficiency and were treated with danazol from 2 months to 30 years. The frequency and severity of acute attacks were registered before......, headache, depression, and/or liver adenomas) occurred in 93 of the 118 patients and led to discontinuation of danazol therapy in 30 patients. CONCLUSIONS: Danazol is highly beneficial in patients with frequent and severe attacks of HAE. Because the risk of adverse effects is high, close monitoring...

Hereditary protein S deficiency presenting with cerebral sinus thrombosis in an adolescent girl

NARCIS (Netherlands)

Koelman, J. H.; Bakker, C. M.; Plandsoen, W. C.; Peeters, F. L.; Barth, P. G.

1992-01-01

A 14-year-old girl, on oral contraceptives for 3 months, presented with cerebral sinus thrombosis. Investigation revealed underlying hereditary protein S deficiency. This uncommon cause of cerebral sinus thrombosis and the possible association with oral contraceptives are discussed

Hereditary haemorrhagic telangiectasia

DEFF Research Database (Denmark)

Kjeldsen, A D; Vase, P; Green, A

1999-01-01

Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by telangiectatic lesions. The disease manifestations are variable and include epistaxis, gastrointestinal bleeding, pulmonary arteriovenous malformations and cerebral arteriovenous malformations. Early...

Hereditary spherocytosis: Consequences of delayed diagnosis

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Sarah C Steward

2014-08-01

Full Text Available Objective: To determine whether patients with undiagnosed hereditary spherocytosis hospitalized for transfusions might have avoided hospitalization via earlier diagnosis. Study design: Charts of all (N = 30 patients with hereditary spherocytosis seen in pediatric hematology at West Virginia University-Charleston were reviewed. Family and transfusion history and presence of neonatal jaundice were recorded. Complete blood count and reticulocyte values during infancy were available for 20 of 30 patients, while baseline steady-state values were available for all 30. Results: Transfusions were given to 22 patients; 12 of 14 with an aplastic crisis were undiagnosed. In 10 of 12, the severity of anemia led to hospitalization (3 to intensive care. All 10 had prior mean corpuscular hemoglobin concentration and/or red cell distribution width elevations and a history of neonatal jaundice; 7 of 10 had a positive family history. Conclusions: Undiagnosed hereditary spherocytosis may lead to inpatient transfusions for severe anemia. Earlier detection of hereditary spherocytosis is easily achievable and may reduce hospitalizations via closer monitoring.

Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing

DEFF Research Database (Denmark)

Rohlin, Anna; Rambech, Eva; Kvist, Anders

2017-01-01

Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel...

Are patients with severe epistaxis caused by hereditary hemorrhagic telangiectasia satisfied with nostril closure surgery?

Science.gov (United States)

Ichimura, Keiichi; Kikuchi, Hisashi; Imayoshi, Shoichiro; Yamauchi, Tomohiko; Ishikawa, Kotaro

2012-02-01

Recurrent epistaxis as a manifestation of hereditary hemorrhagic telangiectasia (HHT) is usually difficult to control. Although no treatment is regarded to be completely efficacious, nostril closure is considered a modality of choice for the most severe cases. The cessation of airflow resulting from this procedure can stop bleeding by minimizing risk factors. However, loss of nasal functions is a disadvantage of nostril closure. We conducted a questionnaire survey of patients who underwent nostril closure surgery, regarding the effects and disadvantages of the operation. Seven patients were asked questions on issues including frequency and severity of epistaxis pre- and post-operatively, satisfaction of treatment, and impairment in daily living activities. Most patients reported complete cessation of bleeding. Some still had bleeding, but the frequency and severity were far lower. No transfusions were required in any of the cases. Patients reported some disadvantages, for example, respiratory, olfactory, and phonatory issues. Six out of seven patients were very satisfied with the outcome of surgery. Nostril closure surgery can remarkably reduce frequency and volume of epistaxis. Our survey indicated that satisfactory results were achieved. However, difficulties caused by complete nasal obstruction varied. Thus, individualized coping strategies are required. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Hereditary gingival fibromatosis: A report of two cases in the same family

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Vanali V Umrania

2016-01-01

Full Text Available Overgrowth of keratinized gingival tissues is a common condition and is described under variety of names. Causes of such enlargement can be medications, hereditary, and/or local irritating factors. Mutation in SOS1, son-of-sevenless gene, is thought to be responsible for hereditary gingival fibromatosis. This report shows a case of 19-year-old male and his 15-year-old sister, with a chief complaint of overgrowth of gingival and irregularly placed teeth. A similar overgrowth was also found in other members of the same family, without any drug history or syndromic conditions. An occurrence of the disease has been found in two generations of this family and therefore, it may be following autosomal dominant trait of inheritance. Since it is idiopathic and has a genetic cause for its occurrence, it cannot be prevented. Both cases underwent a surgical intervention to rectify the abnormality and were followed from 6 months to 1 year, during which there was no recurrence.

Hereditary Persistence of Fetal Hemoglobin Caused by Single Nucleotide Promoter Mutations in Sickle Cell Trait and Hb SC Disease.

Science.gov (United States)

Akinbami, Anthony O; Campbell, Andrew D; Han, Zeqiu J; Luo, Hong-Yuan; Chui, David H K; Steinberg, Martin H

2016-01-01

Hereditary persistence of fetal hemoglobin (HPFH) can be caused by point mutations in the γ-globin gene promoters. We report three rare cases: a child compound heterozygous for Hb S (HBB: c.20A > T) and HPFH with a novel point mutation in the (A)γ-globin gene promoter who had 42.0% Hb S, 17.0% Hb A and 38.0% Hb F; a man with Hb SC (HBB: c.19G > A) disease and a point mutation in the (G)γ-globin gene promoter who had 54.0% Hb S, 18.0% Hb C and 25.0% Hb F; a child heterozygous for Hb S and HPFH due to mutations in both the (A)γ- and (G)γ-globin gene promoters in cis [(G)γ(A)γ(β(+)) HPFH], with 67.0% Hb A, 6.5% Hb S and 25.0% Hb F.

Hereditary & familial colorectal cancer : Identification, characteristics, surveillance

NARCIS (Netherlands)

Kallenberg, F.G.J.

2017-01-01

Of all colorectal cancer (CRC) cases, 15-20% is related to familial or hereditary factors. Diagnosing familial and hereditary CRC syndromes is important for several reasons. One of these is that surveillance colonoscopies can reduce CRC incidence and mortality importantly. A complete family history

Hereditary internal anal sphincter myopathy causing proctalgia fugax and constipation: further clinical and histological characterization in a patient.

Science.gov (United States)

König, P; Ambrose, N S; Scott, N

2000-01-01

Hereditary internal anal sphincter myopathy is a very rare condition, only three families have so far been described in the literature. In this case report further clinical and histological findings of one affected member of one of the above families are presented.

Acutely Onset Amiodarone-Induced Angioedema in a Patient with New Atrial Fibrillation

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Hossein Vakili

2014-01-01

Full Text Available A 50-year-old man was admitted to our emergency department due to new episode of palpitation. He had history of angioplasty of right coronary artery (RCA with drug eluting stent 2 years ago. His electrocardiogram revealed atrial fibrillation (AF. Intravenous amiodarone 150 mg during 10 minutes and then 1 mg/min infusion were started to achieve rate control and pharmacologic conversion to sinus rhythm. After 60 minutes of starting amiodarone infusion, he developed swelling of the skin around his mouth and eyes, and also mucosa of the mouth, eyes and tongue. To conclude, angioedema should be considered a rare side effect of amiodarone which is used broadly in cardiovascular field.

A comprehensive custom panel design for routine hereditary cancer testing: preserving control, improving diagnostics and revealing a complex variation landscape.

Science.gov (United States)

Castellanos, Elisabeth; Gel, Bernat; Rosas, Inma; Tornero, Eva; Santín, Sheila; Pluvinet, Raquel; Velasco, Juan; Sumoy, Lauro; Del Valle, Jesús; Perucho, Manuel; Blanco, Ignacio; Navarro, Matilde; Brunet, Joan; Pineda, Marta; Feliubadaló, Lidia; Capellá, Gabi; Lázaro, Conxi; Serra, Eduard

2017-01-04

We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set. I2HCP changed our diagnostic approach, involving clinicians and a genetic diagnostics team from panel design to reporting. The new strategy improved diagnostic sensitivity, solved uncertain clinical diagnoses and identified mutations in new genes. We assessed the genetic variation in the complete set of hereditary cancer genes, revealing a complex variation landscape that coexists with the disease-causing mutation. We developed, validated and implemented a custom NGS-based strategy for hereditary cancer diagnostics that improved our previous workflows. Additionally, the existence of a rich genetic variation in hereditary cancer genes favors the use of this panel to investigate their role in cancer risk.

Orthodontic treatment for a patient with hereditary angiodema: a case report.

Science.gov (United States)

Waldon, Kate; Barber, Sophy Kathleen; Spencer, Richard James

2015-05-01

Hereditary angiodema (HAE), also known as C1 esterase inhibitor deficiency, causes sufferers to experience episodic subcutaneous and submucosal oedema. These episodes can be triggered by dental treatment and manifest as life-threatening oedematous swelling in the head and neck region. This case report reviews an adolescent with hereditary angiodema whose malocclusion required orthodontic intervention. Due to her complex and unpredictable reaction to dental treatment, various options were explored before determining the appropriate care pathway for this patient. Trial placement of a sectional fixed appliance tested the tissue reaction prior to comprehensive treatment including extractions and fixed orthodontic appliances. This report demonstrates successful interdisciplinary management facilitating orthodontic care in a patient with HAE. © 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Causes of permanent childhood hearing impairment.

Science.gov (United States)

Korver, Anna M H; Admiraal, Ronald J C; Kant, Sarina G; Dekker, Friedo W; Wever, Capi C; Kunst, Henricus P M; Frijns, Johan H M; Oudesluys-Murphy, Anne Marie

2011-02-01

The causes of Permanent Childhood Hearing Impairment (PCHI) are often quoted as being hereditary in 50%, acquired in 25%, and unknown in 25% of cases. Interest in the causes of PCHI has grown recently due to increasing diagnostic possibilities. We investigated the evidence for the reported distribution of these causes. Population-based study and a systematic review. Inclusion criteria for population-based study: children born between 2003 and 2005, resident in The Netherlands at birth, known at an Audiology Center with PCHI at the age of 3-5 years. The causes of PCHI were determined prospectively by detection of congenital cytomegalovirus on dried blood spots and/or genetic diagnostic investigations in addition to reviewing data from medical records. A systematic review was carried out using three terms (hearing loss, infant, and etiology) and limited to articles published between January 1997 and July 2009. Main outcome measures were: the (weighted) proportions of the various causes of PCHI following diagnostic investigations. In the study-population (n = 185) a hereditary cause was found in 38.9%, acquired cause in 29.7%, miscellaneous cause in 7.1%, and the cause remained unknown in 24.3%. The systematic review of the literature (n = 9 articles) resulted in a weighted mean of 30.4% hereditary, 19.2% acquired, and 48.3% unknown causes of PCHI. The systematic review and the results of the population-based study provided little support for the generally accepted distribution of causes of PCHI. Copyright © 2010 The American Laryngological, Rhinological, and Otological Society, Inc.

Hereditary non-polyposis colorectal cancer : Identification of mutation carriers and assessing pathogenicity of mutations

NARCIS (Netherlands)

Niessen, RC; Sijmons, RH; Berends, MJW; Ou, J; Hofstra, RNW; Kleibeuker, JH

2004-01-01

Hereditary non-polyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is an autosomal dominantly inherited disorder that is characterized by susceptibility to colorectal cancer and extracolonic malignancies, in particular endometrial cancer. HNPCC is caused by pathogenic mutations

Hereditary spastic paraplegias: membrane traffic and the motor pathway

OpenAIRE

Blackstone, Craig; O’Kane, Cahir J.; Reid, Evan

2011-01-01

Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent wo...

Mechanistic basis of an epistatic interaction reducing age at onset in hereditary spastic paraplegia.

Science.gov (United States)

Newton, Timothy; Allison, Rachel; Edgar, James R; Lumb, Jennifer H; Rodger, Catherine E; Manna, Paul T; Rizo, Tania; Kohl, Zacharias; Nygren, Anders O H; Arning, Larissa; Schüle, Rebecca; Depienne, Christel; Goldberg, Lisa; Frahm, Christiane; Stevanin, Giovanni; Durr, Alexandra; Schöls, Ludger; Winner, Beate; Beetz, Christian; Reid, Evan

2018-05-01

Many genetic neurological disorders exhibit variable expression within affected families, often exemplified by variations in disease age at onset. Epistatic effects (i.e. effects of modifier genes on the disease gene) may underlie this variation, but the mechanistic basis for such epistatic interactions is rarely understood. Here we report a novel epistatic interaction between SPAST and the contiguous gene DPY30, which modifies age at onset in hereditary spastic paraplegia, a genetic axonopathy. We found that patients with hereditary spastic paraplegia caused by genomic deletions of SPAST that extended into DPY30 had a significantly younger age at onset. We show that, like spastin, the protein encoded by SPAST, the DPY30 protein controls endosomal tubule fission, traffic of mannose 6-phosphate receptors from endosomes to the Golgi, and lysosomal ultrastructural morphology. We propose that additive effects on this pathway explain the reduced age at onset of hereditary spastic paraplegia in patients who are haploinsufficient for both genes.

Hereditary sensory and autonomic neuropathy type IID caused by an SCN9A mutation.

Science.gov (United States)

Yuan, Junhui; Matsuura, Eiji; Higuchi, Yujiro; Hashiguchi, Akihiro; Nakamura, Tomonori; Nozuma, Satoshi; Sakiyama, Yusuke; Yoshimura, Akiko; Izumo, Shuji; Takashima, Hiroshi

2013-04-30

To identify the clinical features of Japanese patients with suspected hereditary sensory and autonomic neuropathy (HSAN) on the basis of genetic diagnoses. On the basis of clinical, in vivo electrophysiologic, and pathologic findings, 9 Japanese patients with sensory and autonomic nervous dysfunctions were selected. Eleven known HSAN disease-causing genes and 5 related genes were screened using a next-generation sequencer. A homozygous mutation, c.3993delGinsTT, was identified in exon 22 of SCN9A from 2 patients/families. The clinical phenotype was characterized by adolescent or congenital onset with loss of pain and temperature sensation, autonomic nervous dysfunctions, hearing loss, and hyposmia. Subsequently, this mutation was discovered in one of patient 1's sisters, who also exhibited sensory and autonomic nervous system dysfunctions, with recurrent fractures being the most predominant feature. Nerve conduction studies revealed definite asymmetric sensory nerve involvement in patient 1. In addition, sural nerve pathologic findings showed loss of large myelinated fibers in patient 1, whereas the younger patient showed normal sural nerve pathology. We identified a novel homozygous mutation in SCN9A from 2 Japanese families with autosomal recessive HSAN. This loss-of-function SCN9A mutation results in disturbances in the sensory, olfactory, and autonomic nervous systems. We propose that SCN9A mutation results in the new entity of HSAN type IID, with additional symptoms including hyposmia, hearing loss, bone dysplasia, and hypogeusia.

Genetics Home Reference: hereditary sensory neuropathy type IA

Science.gov (United States)

... sensory neuropathy type IA Hereditary sensory neuropathy type IA Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary sensory neuropathy type IA is a condition characterized by nerve abnormalities in ...

Angioedema hereditario en Medellín, Colombia: evaluación clínica y de la calidad de vida

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María Dulfary Sánchez

2015-09-01

Conclusión. Este estudio provee información sobre la primera familia caracterizada con angioedema hereditario de tipo 1 en el Valle de Aburrá, Colombia. Aunque para ello se usó un instrumento genérico, se confirmó, además, el efecto negativo de la enfermedad en la calidad de vida de los individuos que la padecen.

Causes of childhood blindness in a developing country and an underdeveloped country.

Science.gov (United States)

Santos-Bueso, E; Dorronzoro-Ramírez, E; Gegúndez-Fernández, J A; Vinuesa-Silva, J M; Vinuesa-Silva, I; García-Sánchez, J

2015-05-01

The causes of childhood blindness depend on factors such as geographic location or the human development index of the populations under study. The main causes in developed countries are genetic and hereditary diseases, while infectious and contagious diseases, together with nutritional and vitamin deficiencies, are the main causes in underdeveloped countries (UDCs). Study of the causes of blindness among children admitted to a regional centre in Nador, Morocco, and among children in Mekele, Ethiopia. The study was carried out in collaboration with two non-governmental organizations based in Madrid, Spain. First, we worked with Fudación Adelias in June 2010, and with Proyecto Visión in October 2012. The study comprised a total of 27 children in Morocco and 85 in Ethiopia. The average age of the children was 10.92 and 6.94 years, respectively. The main causes of blindness in Morocco were hereditary pathologies (25.92%) and refractive errors (14.82%), although trauma (7.40%) and corneal disease (7.40%) are relevant. Among the children from Ethiopia, corneal disease (27.05%) and trauma (20%) were the main causes of blindness, while congenital and hereditary diseases had a lower prevalence (4.70%). The causes of blindness depend on the human development index of the populations under study. While corneal disease and trauma are the main causes observed in UDCs like Ethiopia, hereditary pathologies and refractive errors are the main causes within the Moroccan population studied. A mixed form can be observed in this country, as the cause of blindness found in developed countries, such as congenital and hereditary pathologies which are present alongside the causes normally found in LDCs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

EAMJ Oct Hereditary.indd

African Journals Online (AJOL)

HEREDITARY GINGIVAL FIBROMATOSIS: REPORT OF FAMILY CASE SERIES. E. G. Wagaiyu ... Senior Lecturer, Department of Periodontology/Community and Preventive Dentistry, ... fibrous connective tissue held in chronically inflamed.

Angioedema hereditario: Guía de tratamiento

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Alejandro Malbrán

2012-04-01

Full Text Available El angioedema hereditario (HAE es una enfermedad rara, autosómica dominante, caracterizada por episodios que comprometen la piel, el tracto gastrointestinal y la laringe. Tiene una mortalidad histórica por asfixia del 15 al 50%. Es producida por la deficiencia funcional del C1 inhibidor. La identificación de la bradiquinina como mediador principal ha estimulado el desarrollo de nuevos medicamentos para tratar la enfermedad. El tratamiento del HAE se establece en consensos internacionales. El desarrollo de guías para el tratamiento de la enfermedad permite ordenar el uso de procedimientos diagnósticos y drogas. Describimos aquí algunas características farmacológicas de los medicamentos utilizados en el tratamiento del HAE en la Argentina: el concentrado plasmático de C1 inhibidor, el antagonista de la bradiquinina, icatibant, el andrógeno atenuado danazol y los agentes anti-fibrinolíticos ácidos épsilon aminocaproico (EACA y tranexámico. Asimismo, se describe su forma de uso y del control de los eventos adversos más frecuentes, así como las recomendaciones del último consenso internacional, aplicables para conformar una primera guía de tratamiento del HAE en la Argentina.

Learning about Hereditary Hemochromatosis

Science.gov (United States)

Skip to main content Learning About Hereditary Hemochromatosis Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research ...

Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations

DEFF Research Database (Denmark)

Nielsen, Sofie V,; Stein, Amelie; Dinitzen, Alexander B.

2017-01-01

selected the human mismatch repair protein, MSH2, where missense variants are known to cause the hereditary cancer predisposition disease, known as Lynch syndrome. We show that the majority of disease-causing MSH2 mutations give rise to folding defects and proteasome-dependent degradation rather than...... and for diagnosis of Lynch syndrome, and perhaps other hereditary diseases....

EPO Receptor Gain-of-Function Causes Hereditary Polycythemia, Alters CD34+ Cell Differentiation and Increases Circulating Endothelial Precursors

Science.gov (United States)

Perrotta, Silverio; Cucciolla, Valeria; Ferraro, Marcella; Ronzoni, Luisa; Tramontano, Annunziata; Rossi, Francesca; Scudieri, Anna Chiara; Borriello, Adriana; Roberti, Domenico; Nobili, Bruno; Cappellini, Maria Domenica; Oliva, Adriana; Amendola, Giovanni; Migliaccio, Anna Rita; Mancuso, Patrizia; Martin-Padura, Ines; Bertolini, Francesco; Yoon, Donghoon; Prchal, Josef T.; Della Ragione, Fulvio

2010-01-01

Background Gain-of-function of erythropoietin receptor (EPOR) mutations represent the major cause of primary hereditary polycythemia. EPOR is also found in non-erythroid tissues, although its physiological role is still undefined. Methodology/Principal Findings We describe a family with polycythemia due to a heterozygous mutation of the EPOR gene that causes a G→T change at nucleotide 1251 of exon 8. The novel EPOR G1251T mutation results in the replacement of a glutamate residue by a stop codon at amino acid 393. Differently from polycythemia vera, EPOR G1251T CD34+ cells proliferate and differentiate towards the erythroid phenotype in the presence of minimal amounts of EPO. Moreover, the affected individuals show a 20-fold increase of circulating endothelial precursors. The analysis of erythroid precursor membranes demonstrates a heretofore undescribed accumulation of the truncated EPOR, probably due to the absence of residues involved in the EPO-dependent receptor internalization and degradation. Mutated receptor expression in EPOR-negative cells results in EPOR and Stat5 phosphorylation. Moreover, patient erythroid precursors present an increased activation of EPOR and its effectors, including Stat5 and Erk1/2 pathway. Conclusions/Significance Our data provide an unanticipated mechanism for autosomal dominant inherited polycythemia due to a heterozygous EPOR mutation and suggest a regulatory role of EPO/EPOR pathway in human circulating endothelial precursors homeostasis. PMID:20700488

Hereditary breast cancer

DEFF Research Database (Denmark)

Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie

2014-01-01

Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

Hereditary hemorrhagic telangiectasia: genetics and molecular diagnostics in a new era

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Jamie eMcDonald

2015-01-01

Full Text Available Hereditary hemorrhagic telangiectasia (HHT is a vascular dysplasia characterized by telangiectases and arteriovenous malformations (AVMs in particular locations described in consensus clinical diagnostic criteria published in 2000. Two genes in the transforming growth factor-beta (TGF-β signaling pathway, ENG and ACVRL1, were discovered almost two decades ago, and mutations in these genes have been reported to cause up to 85% of HHT. In our experience, approximately 96% of individuals with HHT have a mutation in these two genes, when published (Curaçao diagnostic criteria for HHT are strictly applied. More recently, two additional genes in the same pathway, SMAD4 and GDF2, have been identified in a much smaller number of patients with a similar or overlapping phenotype to HHT. Yet families still exist with compelling evidence of a hereditary telangiectasia disorder, but no identifiable mutation in a known gene. Recent availability of whole exome and genome testing has created new opportunities to facilitate gene discovery, identify genetic modifiers to explain clinical variability, and potentially define an increased spectrum of hereditary telangiectasia disorders. An expanded approach to molecular diagnostics for inherited telangiectasia disorders that incorporates a multi-gene next generation sequencing (NGS HHT panel is proposed.

Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations

DEFF Research Database (Denmark)

Ferré, Marc; Bonneau, Dominique; Milea, Dan

2009-01-01

We report the results of molecular screening in 980 patients carried out as part of their work-up for suspected hereditary optic neuropathies. All the patients were investigated for Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), by searching for the ten...... and OPA3 mutations in cases of suspected hereditary optic neuropathy, even in absence of a family history of the disease....... novel OPA1 mutations reported here. The statistical analysis of this large set of mutations has led us to propose a diagnostic strategy that should help with the molecular work-up of optic neuropathies. Our results highlight the importance of investigating LHON-causing mtDNA mutations as well as OPA1...

Recommendations regarding splenectomy in hereditary hemolytic anemias

Science.gov (United States)

Iolascon, Achille; Andolfo, Immacolata; Barcellini, Wilma; Corcione, Francesco; Garçon, Loïc; De Franceschi, Lucia; Pignata, Claudio; Graziadei, Giovanna; Pospisilova, Dagmar; Rees, David C.; de Montalembert, Mariane; Rivella, Stefano; Gambale, Antonella; Russo, Roberta; Ribeiro, Leticia; Vives-Corrons, Jules; Martinez, Patricia Aguilar; Kattamis, Antonis; Gulbis, Beatrice; Cappellini, Maria Domenica; Roberts, Irene; Tamary, Hannah

2017-01-01

Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children. PMID:28550188

A Review of Hereditary Fructose Intolerance

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Mogoş Tiberius

2016-03-01

Full Text Available Fructose intolerance is a metabolic disorder with hereditary determinism, clinically manifested on terms of fructose intake. Untreated, hereditary fructose intolerance may result in renal and hepatic failure. Unfortunately, there are no formal diagnostic and surveillance guidelines for this disease. If identified and treated before the occurrence of permanent organ damage, patients can improve their symptoms and self-rated health. Implementation and adherence to a strict fructose free diet is often difficult, but not impossible.

An ochre mutation in the vitamin D receptor gene causes hereditary 1,25-dihydroxyvitamin D3-resistant rickets in three families

International Nuclear Information System (INIS)

Ritchie, H.H.; Hughes, M.R.; Thompson, E.T.; Pike, J.W.; O'Malley, B.W.; Malloy, P.J.; Feldman, D.; Hochberg, Z.

1989-01-01

Hereditary 1,25-dihydroxyvitamin D 3 -resistant rickets is a rare autosomal-recessive disease resulting from target-organ resistance to the action of the active hormonal form of vitamin D. Four affected children from three related families with the classical syndrome of hereditary 1,25-dihydroxyvitamin D 3 -resistant rickets and the absence of detectable binding to the vitamin D receptor (VDR) in cultured fibroblasts or lymphoblasts were examined for genetic abnormalities in the VDR gene. Genomic DNA from Epstein-Barr virus-transformed lymphoblasts of eight family members was isolated and amplified by polymerase chain reaction techniques. Amplified fragments containing the eight structural exons encoding the VDR protein were sequenced. The DNA from all affected children exhibited a single C → A base substitution within exon 7 at nucleotide 970. Although the affected children were all homozygotic for the mutation, the four parents tested all exhibited both wild-type and mutant alleles, indicating a heterozygous state. Recreated mutant receptor exhibited no specific 1,25-[ 3 H]dihydroxyvitamin D 3 binding and failed to activate a cotransfected VDR promoter-reporter gene construct. Thus these findings identify an ochre mutation in a human steroid hormone receptor in patients with hereditary 1,25-dihydroxyvitamin D 3 -resistant rickets

Revisited diagnostics of hereditary epidermolysis bullosa

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V. I. Albanova

2014-01-01

Full Text Available Hereditary epidermolysis bullosa is a big group of hereditary diseases with the main manifestations in the form of blisters on the skin and mucous coat after slight mechanical injuries. It is not always possible to diagnose this disease based on the clinical picture. The article discusses current laboratory diagnostics methods for hereditary epidermolysis bullosa including immunofluorescence antigen mapping (IFM, transmission electron microscopy (TEM and genetic analysis (molecular or DNA diagnostics as well as their advantages and disadvantages. TEM determines the micro splitting level and nature of ultrafine changes in the area of the dermoepidermal junction; at the same time, such tests need special expensive equipment. Substantial experience is also needed to analyze the resulting submicroscopic images. IFM determines whether expression of the affected protein related to the disease development is reduced or absent; however, invalid (false positive or false negative results can be obtained in patients with the reduced expression of the affected protein. Genetic analysis plays a key role for prenatal diagnostics. Therefore, to make an exact diagnosis of hereditary epidermolysis bullosa, it is expedient to apply IFM, TEM and genetic analysis. The need to set an exact diagnosis of the disease is related to the fact that the promising treatment methods being currently developed are aimed at treating patients with certain forms of the disease.

Evidence-based management of epistaxis in hereditary haemorrhagic telangiectasia.

Science.gov (United States)

Syed, I; Sunkaraneni, V S

2015-05-01

There are currently no guidelines in the UK for the specific management of hereditary haemorrhagic telangiectasia related epistaxis. The authors aimed to review the literature and provide an algorithm for the management of hereditary haemorrhagic telangiectasia related epistaxis. The Medline and Embase databases were interrogated on 15 November 2013 using the search items 'hereditary haemorrhagic telangiectasia' (title), 'epistaxis' (title) and 'treatment' (title and abstract), and limiting the search to articles published in English. A total of 46 publications were identified, comprising 1 systematic review, 2 randomised, controlled trials, 27 case series, 9 case reports, 4 questionnaire studies and 3 in vitro studies. There is a lack of high-level evidence for the use of many of the available treatments for the specific management of epistaxis in hereditary haemorrhagic telangiectasia. Current management should be based on a multidisciplinary team approach involving both a hereditary haemorrhagic telangiectasia physician and an ENT surgeon, especially when systemic therapy is being considered. The suggested treatment algorithm considers that the severity of epistaxis merits intervention at different levels of the treatment ladder. The patient should be assessed using a reproducible validated assessment tool, for example an epistaxis severity score, to guide treatment. More research is required, particularly in the investigation of topical agents targeting the development and fragility of telangiectasiae in hereditary haemorrhagic telangiectasia.

N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom

NARCIS (Netherlands)

Kalaydjieva, L.; Gresham, D.; Gooding, R.; Heather, L.; Baas, F.; de Jonge, R.; Blechschmidt, K.; Angelicheva, D.; Chandler, D.; Worsley, P.; Rosenthal, A.; King, R. H.; Thomas, P. K.

2000-01-01

Hereditary motor and sensory neuropathies, to which Charcot-Marie-Tooth (CMT) disease belongs, are a common cause of disability in adulthood. Growing awareness that axonal loss, rather than demyelination per se, is responsible for the neurological deficit in demyelinating CMT disease has focused

Genetics Home Reference: hereditary leiomyomatosis and renal cell cancer

Science.gov (United States)

... Home Health Conditions HLRCC Hereditary leiomyomatosis and renal cell cancer Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary leiomyomatosis and renal cell cancer ( HLRCC ) is a disorder in which affected individuals ...

Organization and Running of the First Comprehensive Hereditary Cancer Clinic in India

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Rajkumar T

2005-11-01

Full Text Available Abstract Hereditary cancers are thought to account for around 5% of cancers, particularly breast/ovarian and colorectal cancers. In India there is a paucity of data on hereditary cancers and the mutations in some of the common genes linked to hereditary cancers, such as BRCA1, BRCA2, hMSH2 and hMLH1. The country's first comprehensive hereditary cancer clinic was established in February 2002. The article describes the organization and running of the Clinic. It also discusses some of the social issues relevant to the given population in running the Hereditary Cancer Clinic.

Recurrent IVF failure and hereditary thrombophilia.

Science.gov (United States)

Safdarian, Leila; Najmi, Zahra; Aleyasin, Ashraf; Aghahosseini, Marzieh; Rashidi, Mandana; Asadollah, Sara

2014-07-01

The largest percentage of failed invitro fertilization (IVF (cycles, are due to lack of implantation. As hereditary thrombophilia can cause in placentation failure, it may have a role in recurrent IVF failure. Aim of this case-control study was to determine whether hereditary thrombophilia is more prevalent in women with recurrent IVF failures. Case group comprised 96 infertile women, with a history of recurrent IVF failure. Control group was comprised of 95 healthy women with proven fertility who had conceived spontaneously. All participants were assessed for the presence of inherited thrombophilias including: factor V Leiden, methilen tetrahydrofolate reductase (MTHFR) mutation, prothrombin mutation, homocystein level, protein S and C deficiency, antithrombin III (AT-III) deficiency and plasminogen activator inhibitor-1 (PAI-1) mutation. Presence of thrombophilia was compared between groups. Having at least one thrombophilia known as a risk factor for recurrent IVF failure (95% CI=1.74-5.70, OR=3.15, p=0.00). Mutation of factor V Leiden (95% CI=1.26-10.27, OR=3.06, P=0.01) and homozygote form of MTHFR mutation (95% CI=1.55-97.86, OR=12.33, p=0.05) were also risk factors for recurrent IVF failure. However, we could not find significant difference in other inherited thrombophilia's. Inherited thrombophilia is more prevalent in women with recurrent IVF failure compared with healthy women. Having at least one thrombophilia, mutation of factor V Leiden and homozygote form of MTHFR mutation were risk factors for recurrent IVF failure.

Comprehensive mutational screening in a cohort of Danish families with hereditary congenital cataract

DEFF Research Database (Denmark)

Hansen, Lars; Mikkelsen, Annemette; Nürnberg, Peter

2009-01-01

, and a gene conversion is the most likely mutational event causing this variant. Ten families had microcornea cataract, and a mutation was identified in eight of those. Most families displayed mixed phenotypes with nuclear, lamellar, and polar opacities and no apparent genotype-phenotype correlation emerged......PURPOSE: Identification of the causal mutations in 28 unrelated families and individuals with hereditary congenital cataract identified from a national Danish register of hereditary eye diseases. Seven families have been published previously, and the data of the remaining 21 families are presented...... together with an overview of the results in all families. METHODS: A combined screening approach of linkage analysis and sequencing of 17 cataract genes were applied to mutation analyses of total 28 families. RESULTS: The study revealed a disease locus in seven of eight families that were amenable...

Therapeutic Strategies for Hereditary Kidney Cancer.

Science.gov (United States)

Sidana, Abhinav; Srinivasan, Ramaprasad

2016-08-01

The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers.

Attitude towards pre-implantation genetic diagnosis for hereditary cancer

NARCIS (Netherlands)

Lammens, Chantal; Bleiker, Eveline; Aaronson, Neil; Vriends, Annette; Ausems, Margreet; Jansweijer, Maaike; Wagner, Anja; Sijmons, Rolf; van den Ouweland, Ans; van der Luijt, Rob; Spruijt, Liesbeth; Gómez García, Encarna; Ruijs, Mariëlle; Verhoef, Senno

2009-01-01

The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition.

HSPB1 mutations causing hereditary neuropathy in humans disrupt non-cell autonomous protection of motor neurons.

Science.gov (United States)

Heilman, Patrick L; Song, SungWon; Miranda, Carlos J; Meyer, Kathrin; Srivastava, Amit K; Knapp, Amy; Wier, Christopher G; Kaspar, Brian K; Kolb, Stephen J

2017-11-01

Heat shock protein beta-1 (HSPB1), is a ubiquitously expressed, multifunctional protein chaperone. Mutations in HSPB1 result in the development of a late-onset, distal hereditary motor neuropathy type II (dHMN) and axonal Charcot-Marie Tooth disease with sensory involvement (CMT2F). The functional consequences of HSPB1 mutations associated with hereditary neuropathy are unknown. HSPB1 also displays neuroprotective properties in many neuronal disease models, including the motor neuron disease amyotrophic lateral sclerosis (ALS). HSPB1 is upregulated in SOD1-ALS animal models during disease progression, predominately in glial cells. Glial cells are known to contribute to motor neuron loss in ALS through a non-cell autonomous mechanism. In this study, we examined the non-cell autonomous role of wild type and mutant HSPB1 in an astrocyte-motor neuron co-culture model system of ALS. Astrocyte-specific overexpression of wild type HSPB1 was sufficient to attenuate SOD1(G93A) astrocyte-mediated toxicity in motor neurons, whereas, overexpression of mutHSPB1 failed to ameliorate motor neuron toxicity. Expression of a phosphomimetic HSPB1 mutant in SOD1(G93A) astrocytes also reduced toxicity to motor neurons, suggesting that phosphorylation may contribute to HSPB1 mediated-neuroprotection. These data provide evidence that astrocytic HSPB1 expression may play a central role in motor neuron health and maintenance. Copyright © 2017 Elsevier Inc. All rights reserved.

RBEs and cytogenetic hereditary effects induced by neutron beams in mice

International Nuclear Information System (INIS)

Du Zeji; Li Yanyi; Liu Degui

1994-01-01

The RBEs and cytogenetic hereditary effects of different dose of neutron beams on chromosome aberrations and micronuclei of bone marrow cells in mice were observed. The results indicated that micronuclei frequency of occurrence and chromosome aberration frequency caused by neutrons increased with doses. The relationship was feasible to Y aD n . The lower energy of neutrons had the smaller value of RBE. RBE determined by CSACR were larger than that by MNCF. RBEs decreased with increasing of neutron doses, especially within the low range of doses. There was a linear relationship between CSACR and MNCF caused by neutron beams and γ-ray

An ochre mutation in the vitamin D receptor gene causes hereditary 1,25-dihydroxyvitamin D sub 3 -resistant rickets in three families

Energy Technology Data Exchange (ETDEWEB)

Ritchie, H.H.; Hughes, M.R.; Thompson, E.T.; Pike, J.W.; O' Malley, B.W. (Baylor College of Medicine, Houston, TX (USA)); Malloy, P.J.; Feldman, D. (Stanford Univ. School of Medicine, CA (USA)); Hochberg, Z. (Rambam Medical Center, Haifa (Israel))

1989-12-01

Hereditary 1,25-dihydroxyvitamin D{sub 3}-resistant rickets is a rare autosomal-recessive disease resulting from target-organ resistance to the action of the active hormonal form of vitamin D. Four affected children from three related families with the classical syndrome of hereditary 1,25-dihydroxyvitamin D{sub 3}-resistant rickets and the absence of detectable binding to the vitamin D receptor (VDR) in cultured fibroblasts or lymphoblasts were examined for genetic abnormalities in the VDR gene. Genomic DNA from Epstein-Barr virus-transformed lymphoblasts of eight family members was isolated and amplified by polymerase chain reaction techniques. Amplified fragments containing the eight structural exons encoding the VDR protein were sequenced. The DNA from all affected children exhibited a single C {yields} A base substitution within exon 7 at nucleotide 970. Although the affected children were all homozygotic for the mutation, the four parents tested all exhibited both wild-type and mutant alleles, indicating a heterozygous state. Recreated mutant receptor exhibited no specific 1,25-({sup 3}H)dihydroxyvitamin D{sub 3} binding and failed to activate a cotransfected VDR promoter-reporter gene construct. Thus these findings identify an ochre mutation in a human steroid hormone receptor in patients with hereditary 1,25-dihydroxyvitamin D{sub 3}-resistant rickets.

Squamous cell carcinoma complicating an hereditary epidermo-lysis bullosa

International Nuclear Information System (INIS)

Mseddi, M.; Turki, H.; Marrekchi, S.; Abdelmaksoud, W.; Masmoudi, A.; Bouassida, S.; Zahaf, A.

2004-01-01

The dystrophic form of hereditary epidermo-lysis bullosa is associated with an increased frequency of squamous cell carcinoma. We report a new case. An 18-year-old patient, carrying a Hallopeau Siemens hereditary epidermo-lysis bullosa, presented a subcutaneous nodular lesion, for 1 year that ulcerated and budded with inguinal lymphadenopathy. The histological study ted to the conclusion of a well differentiated squamous cell carcinoma. The patient was treated surgically. Tumor and metastatic lymph nodes were excised. A radiotherapy was decided but the postoperative course was fatal due to an infection and to a deterioration of her general condition. Squamous cell carcinoma frequently occurs on the cicatricial lesion of hereditary epidermo-lysis bullosa and usually affects males with recessive hereditary epidermo-lysis bullosa. Metastases are frequent, precocious and multiple. The treatment may be surgical. The particularities of our observation are the young age of patient and the localization. (author)

Visão atual da hemocromatose hereditária Current approach to hereditary hemochromatosis

Directory of Open Access Journals (Sweden)

Rodolfo Delfini Cançado

2010-01-01

Full Text Available A hemocromatose hereditária (HH está relacionada a diversos distúrbios do metabolismo do ferro que ocasionam sua sobrecarga tecidual. A HH clássica está associada às mutações do gene HFE (homozigose para C282Y ou duplo heterozigose para C282Y/H63D, sendo encontrada quase exclusivamente em descendentes do norte Europeu. A hemocromatose hereditária, quando não relacionada ao gene HFE, é causada por mutações de outros genes, recentemente identificados, envolvidos no metabolismo do ferro. Hepcedina é o hormônio regulador do ferro que inibe a ferroportina, proteína exportadora de ferro dos enterócitos e dos macrófagos; um defeito na expressão do gene da hepcedina ou na sua função costuma ser a causa da maioria dos tipos de hemocromatose hereditária. Os alvos acometidos pela HH são órgãos e tecidos - fígado, coração, pâncreas, articulações e pele -, sendo a cirrose e o diabetes melito os sinais tardios da doença em pacientes com expressivo aumento da concentração hepática de ferro. Pacientes com diagnóstico estabelecido de hemocromatose hereditária e sobrecarga de ferro devem ser tratados com flebotomia para a obtenção de depleção do ferro do organismo; em seguida, com flebotomia de manutenção. As causas mais frequentes de morte por hemocromatose hereditária são câncer hepático, cirrose, miocardiopatia e diabete; entretanto, pacientes submetidos à depleção do ferro de maneira satisfatória e antes do desenvolvimento da cirrose ou da diabete podem ter sobrevida normal.Hereditary hemochromatosis refers to several inherited disorders of the iron metabolism that lead to tissue iron overload. Classical hereditary hemochromatosis is associated with mutations of the HFE gene (C282Y homozygotes or C282Y/H63D compound heterozygotes and is almost exclusively found in populations of northern European descent. Non-HFE-associated hereditary hemochromatosis is caused by mutations in other recently identified genes

Calcium absorption, kinetics, bone density, and bone structure in patients with hereditary vitamin D-resistant rickets

Science.gov (United States)

Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is caused by mutations in the vitamin D receptor gene. Children with HVDRR suffer from severe hypocalcemia and rickets that are treatable with extremely high-dose calcium supplements. Surprisingly, spontaneous recovery of calcium metabolis...

The prevalence of depression in hereditary spastic paraplegia.

Science.gov (United States)

Vahter, L; Braschinsky, M; Haldre, S; Gross-Paju, K

2009-09-01

To evaluate the prevalence of depression and sensitivity and specificity of the single-item interview 'Are you depressed?' for people with hereditary spastic paraplegia in Estonia. Single-item interview 'Are you depressed?' was used as a screening question for depression; all participants then completed the Beck Depression Inventory. People with hereditary spastic paraplegia identified from the epidemiological database who agreed to participate in the study. Beck Depression Inventory, clinical interview. The epidemiological database consisted of 59 patients with clinically confirmed diagnosis of hereditary spastic paraplegia. Forty-eight of these consented to participate in the study. The Beck Depression Inventory score was higher than cut-off point in 58% (28/48) and lower in 42% (20/48). Of the study group, 44% (21/48) had mild, 13% (6/48) moderate and one person revealed severe depression. There was a statistically significant correlation between Beck Depression Inventory score and level of mobility; no other significant correlations with other measures were detected. Of the participants, 54% (26/48) had subjective complaints about depression and answered 'Yes' to the single-item interview 'Are you depressed?'. The sensitivity of the one-item interview in the hereditary spastic paraplegia group was 75% and specificity 75%. Our results show that mild depression is prevalent among people with hereditary spastic paraplegia. Although the single question may be helpful, it cannot be relied upon entirely when assessing a person for depression.

Causes of permanent childhood hearing impairment

NARCIS (Netherlands)

Korver, Anna M. H.; Admiraal, Ronald J. C.; Kant, Sarina G.; Dekker, Friedo W.; Wever, Capi C.; Kunst, Henricus P. M.; Frijns, Johan H. M.; Oudesluys-Murphy, Anne Marie; Oudesluys-Murphy, A. M.; Korver, A. M. H.; Frijns, J. H. M.; Wever, C. C.; Konings, S.; Beers, W.; Dekker, F. W.; de Vries, J. J. C.; Vossen, A. C. T. M.; Kant, S. G.; van den Akker-van Marle, M. E.; Rieffe, C.; Ens-Dokkum, M. H.; van Straaten, H. L. M.; Uilenburg, N. N.; Elvers, B.; Loeber, G.; Meuwese-Jongejeugd, J.; Maré, M. J.; Van Zanten, G. A.; Goedegebure, A.; Coster, F.; Goverts, S. T.; Admiraal, R. J. C.; Cremers, C. W. R. J.; Kunst, H. P. M.; de Leeuw, M.; Dijkhuizen, J.; Scharloo, M.; Hoeben, D.; Rijpma, G.; Graef, W.; Linschoten, D.; Kuijper, J.; Hof, N. J.; Pans, D.; Jorritsma, F.; van Beurden, M.; ter Huurne, C. T.; Brienesse, P.; Koldewijn, G. J.; Letourneur, K. G.

2011-01-01

The causes of Permanent Childhood Hearing Impairment (PCHI) are often quoted as being hereditary in 50%, acquired in 25%, and unknown in 25% of cases. Interest in the causes of PCHI has grown recently due to increasing diagnostic possibilities. We investigated the evidence for the reported

Causes of permanent childhood hearing impairment

NARCIS (Netherlands)

Korver, A.M.; Admiraal, R.J.C.; Kant, S.G.; Dekker, F.W.; Wever, C.; Kunst, H.P.M.; Frijns, J.H.; Oudesluys-Murphy, A.M.

2011-01-01

INTRODUCTION: The causes of Permanent Childhood Hearing Impairment (PCHI) are often quoted as being hereditary in 50%, acquired in 25%, and unknown in 25% of cases. Interest in the causes of PCHI has grown recently due to increasing diagnostic possibilities. We investigated the evidence for the

Inherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy.

Science.gov (United States)

Chance, Phillip F

2006-01-01

Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers. The histopathological changes observed in peripheral nerves of HNPP patients include segmental demyelination and tomaculous or "sausage-like" formations. Mild overlap of clinical features with Charcot-Marie-Tooth (CMT) disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed as having CMT1. HNPP and CMT1 are both demyelinating neuropathies, however, their clinical, pathological, and electrophysiological features are quite distinct. HNPP is most frequently associated with a 1.4-Mb pair deletion on chromosome 17p12. A duplication of the identical region leads to CMT1A. Both HNPP and CMT1A result from a dosage effect of the PMP22 gene, which is contained within the deleted/duplicated region. This is reflected in reduced mRNA and protein levels in sural nerve biopsy samples from HNPP patients. Treatment for HNPP consists of preventative and symptom-easing measures. Hereditary neuralgic amyotrophy (HNA; also called familial brachial plexus neuropathy) is an autosomal-dominant disorder causing episodes of paralysis and muscle weakness initiated by severe pain. Individuals with HNA may suffer repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb. The onset of HNA is at birth or later in childhood with prognosis for recovery usually favorable; however, persons with HNA may have permanent residual neurological dysfunction following attack(s). Episodes are often

Opinions of hearing parents about the causes of hearing impairment of their children with biallelic GJB2 mutations.

Science.gov (United States)

Solovyev, Aisen V; Dzhemileva, Lilya U; Posukh, Olga L; Barashkov, Nikolay A; Bady-Khoo, Marita S; Lobov, Semen L; Popova, Natalya Yu; Romanov, Georgii P; Sazonov, Nikolay N; Bondar, Alexander A; Morozov, Igor V; Tomsky, Mikhail I; Fedorova, Sardana A; Khusnutdinova, Elza K

2017-07-01

Hereditary hearing impairment (HI) caused by recessive GJB2 mutations is a frequent sensory disorder. The results of the molecular-based studies of HI are widely used in various genetic test systems. However, the ethical aspects are less described than the genetic aspects. The concerns expressed by individuals from groups with genetic risks must be included in the counseling of patients and their families. For evaluation of subjective opinions of hearing parents about the presumed causes of HI of their children, we analyze the cohort of parents having children with confirmed hereditary HI caused by biallelic recessive GJB2 mutations (in a homozygous or a compound heterozygous state). This study included 70 deaf children with HI due to mutations in the GJB2 gene and 91 questionnaires about the presumed causes of their deafness filled by their parents. Most of the parents at 78% (CI 68.4-85.4%) attributed their children's HI to "non-hereditary" causes and 22% (CI 14.7-31.6%) to "hereditary" causes (p < 0.05). Therefore, the prior opinions of the parents did not correspond to positive GJB2 genetic testing results. The subjective opinions of parents are probably partly based on family history, since respondents with deaf relatives in their pedigree more likely supposed hereditary causes for HI in their children than the respondents without deaf relatives (p < 0.001).

Knowledge regarding basic concepts of hereditary cancers, and the ...

African Journals Online (AJOL)

Background. In families with hereditary cancer, at-risk individuals can benefit from genetic counselling and testing. General practitioners (GPs) are ideally placed to identify such families and refer them appropriately. Objective. To assess the practices, knowledge and attitudes of GPs regarding common hereditary cancers.

[Mutation analysis of FGFR3 gene in a family featuring hereditary dwarfism].

Science.gov (United States)

Zhang, Qiong; Jiang, Hai-ou; Quan, Qing-li; Li, Jun; He, Ting; Huang, Xue-shuang

2011-12-01

To investigate the clinical symptoms and potential mutation in FGFR3 gene for a family featuring hereditary dwarfism in order to attain diagnosis and provide prenatal diagnosis. Five patients and two unaffected relatives from the family, in addition with 100 healthy controls, were recruited. Genome DNA was extracted. Exons 10 and 13 of the FGFR3 gene were amplified using polymerase chain reaction (PCR). PCR products were sequenced in both directions. All patients had similar features including short stature, short limbs, lumbar hyperlordosis but normal craniofacial features. A heterozygous mutation G1620T (N540K) was identified in the cDNA from all patients but not in the unaffected relatives and 100 control subjects. A heterozygous G380R mutation was excluded. The hereditary dwarfism featured by this family has been caused by hypochondroplasia (HCH) due to a N540K mutation in the FGFR3 gene.

Hereditary familial vestibular degenerative diseases.

NARCIS (Netherlands)

Sun, J.; Alphen, A.M. van; Wagenaar, M.; Huygen, P.L.M.; Hoogenraad, C.C.; Hasson, T.; Koekkoek, S.K.; Bohne, B.A.; Zeeuw, C.I. de

2001-01-01

Identification of genes involved in hereditary vestibular disease is growing at a remarkable pace. Mutant mouse technology can be an important tool for understanding the biological mechanism of human vestibular diseases.

Subtle neuropsychiatric and neurocognitive changes in hereditary gelsolin amyloidosis (AGel amyloidosis)

OpenAIRE

Kantanen, Mari; Kiuru-Enari, Sari; Salonen, Oili; Kaipainen, Markku; Hokkanen, Laura

2014-01-01

Hereditary gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA). To investigate further if AGel amyloidosis carries a risk for a specific neuro...

Open-heart surgery using a centrifugal pump: a case of hereditary spherocytosis.

Science.gov (United States)

Matsuzaki, Yuichi; Tomioka, Hideyuki; Saso, Masaki; Azuma, Takashi; Saito, Satoshi; Aomi, Shigeyuki; Yamazaki, Kenji

2016-08-26

Hereditary spherocytosis is a genetic, frequently familial hemolytic blood disease characterized by varying degrees of hemolytic anemia, splenomegaly, and jaundice. There are few reports on adult open-heart surgery for patients with hereditary spherocytosis. We report a rare case of an adult open-heart surgery associated with hereditary spherocytosis. A 63-year-old man was admitted for congestive heart failure due to bicuspid aortic valve, aortic valve regurgitation, and sinus of subaortic aneurysm. The family history, the microscopic findings of the blood smear, and the characteristic osmotic fragility confirmed the diagnosis of hereditary spherocytosis. Furthermore, splenectomy had not been undertaken preoperatively. The patient underwent a successful operation by means of a centrifugal pump. Haptoglobin was used during the cardiopulmonary bypass, and a biological valve was selected to prevent hemolysis. No significant hemolysis occurred intraoperatively or postoperatively. There are no previous reports of patients with hereditary spherocytosis, and bicuspid aortic valve. We have successfully performed an adult open-heart surgery using a centrifugal pump in an adult patient suffering from hereditary spherocytosis and bicuspid aortic valve.

Hereditary lymphedema of the leg – A Case Report

NARCIS (Netherlands)

Heinig, Birgit; Lotti, T.; Tchernev, Georgi; Wollina, Uwe

2017-01-01

Primary of hereditary lymphedema is a rare but progressive disease. It is yet not curable. We present a 48-year-old male patient with hereditary lymphedema of his left leg, that was realised by minor trauma (able twist) when he was seven years old. He had never been treated for lymphedema but

SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis

OpenAIRE

Orlacchio, Antonio; Babalini, Carla; Borreca, Antonella; Patrono, Clarice; Massa, Roberto; Basaran, Sarenur; Munhoz, Renato P.; Rogaeva, Ekaterina A.; St George-Hyslop, Peter H.; Bernardi, Giorgio; Kawarai, Toshitaka

2010-01-01

The mutation of the spatacsin gene is the single most common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene. The inclusion criterion was a diagnosis of clinically definite ...

Genetic disorder in carbohydrates metabolism: hereditary fructose intolerance associated with celiac disease.

Science.gov (United States)

Păcurar, Daniela; Leşanu, Gabriela; Dijmărescu, Irina; Ţincu, Iulia Florentina; Gherghiceanu, Mihaela; Orăşeanu, Dumitru

2017-01-01

Celiac disease (CD) has been associated with several genetic and immune disorders, but association between CD and hereditary fructose intolerance (HFI) is extremely rare. HFI is an autosomal recessive disease caused by catalytic deficiency of aldolase B (fructose-1,6-bisphosphate aldolase). We report the case of a 5-year-old boy suffering from CD, admitted with an initial diagnosis of Reye's-like syndrome. He presented with episodic unconsciousness, seizures, hypoglycemia, hepatomegaly and abnormal liver function. The patient has been on an exclusion diet for three years, but he still had symptoms: stunting, hepatomegaly, high transaminases, but tissue transglutaminase antibodies were negative. Liver biopsy showed hepatic steatosis and mitochondrial damage. The dietary history showed an aversion to fruits, vegetables and sweet-tasting foods. The fructose tolerance test was positive, revealing the diagnostic of hereditary fructose intolerance. Appropriate dietary management and precautions were recommended. The patient has been symptom-free and exhibited normal growth and development until 10 years of age.

Diagnosis and management of hereditary hemochromatosis.

Science.gov (United States)

Salgia, Reena J; Brown, Kimberly

2015-02-01

Hereditary hemochromatosis is a rare genetic disorder that can have significant clinical consequences. Hemochromatosis is associated with iron overload, and can initially be recognized through laboratory testing for serum ferritin and transferrin saturation. Genetic testing for the HFE mutation can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease. The main pathway resulting in iron overload is through altered hepcidin levels. Treatment of patients with the clinical phenotype of hereditary hemochromatosis is commonly through phlebotomy for removal of excess iron stores. This article highlights the current information and data regarding the diagnosis and management of hemochromatosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetics of Hereditary Ataxia in Scottish Terriers.

Science.gov (United States)

Urkasemsin, G; Nielsen, D M; Singleton, A; Arepalli, S; Hernandez, D; Agler, C; Olby, N J

2017-07-01

Scottish Terriers have a high incidence of juvenile onset hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex and causing slowly progressive cerebellar dysfunction. To identify chromosomal regions associated with hereditary ataxia in Scottish Terriers. One hundred and fifty-three Scottish Terriers were recruited through the Scottish Terrier Club of America. Prospective study. Dogs were classified as affected if they had slowly progressive cerebellar signs. When possible, magnetic resonance imaging and histopathological evaluation of the brain were completed as diagnostic aids. To identify genomic regions connected with the disease, genome-wide mapping was performed using both linkage- and association-based approaches. Pedigree evaluation and homozygosity mapping were also performed to examine mode of inheritance and to investigate the region of interest, respectively. Linkage and genome-wide association studies in a cohort of Scottish Terriers both identified a region on CFA X strongly associated with the disease trait. Homozygosity mapping revealed a 4 Mb region of interest. Pedigree evaluation failed to identify the possible mode of inheritance due to the lack of complete litter information. This finding suggests that further genetic investigation of the potential region of interest on CFA X should be considered in order to identify the causal mutation as well as develop a genetic test to eliminate the disease from this breed. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11.

Directory of Open Access Journals (Sweden)

Rita-Eva Varga

2015-08-01

Full Text Available Hereditary spastic paraplegia (HSP is characterized by a dying back degeneration of corticospinal axons which leads to progressive weakness and spasticity of the legs. SPG11 is the most common autosomal-recessive form of HSPs and is caused by mutations in SPG11. A recent in vitro study suggested that Spatacsin, the respective gene product, is needed for the recycling of lysosomes from autolysosomes, a process known as autophagic lysosome reformation. The relevance of this observation for hereditary spastic paraplegia, however, has remained unclear. Here, we report that disruption of Spatacsin in mice indeed causes hereditary spastic paraplegia-like phenotypes with loss of cortical neurons and Purkinje cells. Degenerating neurons accumulate autofluorescent material, which stains for the lysosomal protein Lamp1 and for p62, a marker of substrate destined to be degraded by autophagy, and hence appears to be related to autolysosomes. Supporting a more generalized defect of autophagy, levels of lipidated LC3 are increased in Spatacsin knockout mouse embryonic fibrobasts (MEFs. Though distinct parameters of lysosomal function like processing of cathepsin D and lysosomal pH are preserved, lysosome numbers are reduced in knockout MEFs and the recovery of lysosomes during sustained starvation impaired consistent with a defect of autophagic lysosome reformation. Because lysosomes are reduced in cortical neurons and Purkinje cells in vivo, we propose that the decreased number of lysosomes available for fusion with autophagosomes impairs autolysosomal clearance, results in the accumulation of undegraded material and finally causes death of particularly sensitive neurons like cortical motoneurons and Purkinje cells in knockout mice.

Presymptomatic diagnosis using a deletion of a single codon in families with hereditary non-polyposis colorectal cancer

DEFF Research Database (Denmark)

Ripa, Rasmus S.; Katballe, Niels; Wikman, Friedrik P.

2005-01-01

The diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is often confirmed by a mutation in one of several mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Presymptomatic diagnosis requires the identification of a mutation causing the disease. Three different deletions...

Genetic linkage analyses and Cx50 mutation detection in a large multiplex Chinese family with hereditary nuclear cataract.

Science.gov (United States)

He, Wei; Li, Xin; Chen, Jiajing; Xu, Ling; Zhang, Feng; Dai, Qiushi; Cui, Hao; Wang, Duen-Mei; Yu, Jun; Hu, Songnian; Lu, Shan

2011-03-01

The aim of the study was to characterize the underlying mutation in a large multiplex Chinese family with hereditary nuclear cataract. A 6-generation Chinese family having hereditary nuclear cataract was recruited and clinically verified. Blood DNA samples were obtained from 53 available family members. Linkage analyses were performed on the known candidate regions for hereditary cataract with 36 polymorphic microsatellite markers. To identify mutations related to cataract, a direct sequencing approach was applied to a candidate gene residing in our linkage locus. A linkage locus was identified with a maximum 2-point LOD score of 4.31 (recombination fraction = 0) at marker D1S498 and a maximum multipoint LOD score of 5.7 between markers D1S2344 and D1S498 on chromosome 1q21.1, where the candidate gene Cx50 is located. Direct sequencing of Cx50 showed a 139 G to A transition occurred in all affected family members. This transitional mutation resulted in a replacement of aspartic acid by asparagine at residue 47 (D47N) and led to a loss-of-function of the protein. The D47N mutation of Cx50 causes the hereditary nuclear cataract in this family in an autosomal dominant mode of inheritance with incomplete penetrance.

HSJ1-related hereditary neuropathies: novel mutations and extended clinical spectrum.

Science.gov (United States)

Gess, Burkhard; Auer-Grumbach, Michaela; Schirmacher, Anja; Strom, Tim; Zitzelsberger, Manuela; Rudnik-Schöneborn, Sabine; Röhr, Dominik; Halfter, Hartmut; Young, Peter; Senderek, Jan

2014-11-04

To determine the nature and frequency of HSJ1 mutations in patients with hereditary motor and hereditary motor and sensory neuropathies. Patients were screened for mutations by genome-wide or targeted linkage and homozygosity studies, whole-exome sequencing, and Sanger sequencing. RNA and protein studies of skin fibroblasts were used for functional characterization. We describe 2 additional mutations in the HSJ1 gene in a cohort of 90 patients with autosomal recessive distal hereditary motor neuropathy (dHMN) and Charcot-Marie-Tooth disease type 2 (CMT2). One family with a dHMN phenotype showed the homozygous splice-site mutation c.229+1G>A, which leads to retention of intron 4 in the HSJ1 messenger RNA with a premature stop codon and loss of protein expression. Another family, presenting with a CMT2 phenotype, carried the homozygous missense mutation c.14A>G (p.Tyr5Cys). This mutation was classified as likely disease-related by several automatic algorithms for prediction of possible impact of an amino acid substitution on the structure and function of proteins. Both mutations cosegregated with autosomal recessive inheritance of the disease and were absent from the general population. Taken together, in our cohort of 90 probands, we confirm that HSJ1 mutations are a rare but detectable cause of autosomal recessive dHMN and CMT2. We provide clinical and functional information on an HSJ1 splice-site mutation and report the detailed phenotype of 2 patients with CMT2, broadening the phenotypic spectrum of HSJ1-related neuropathies. © 2014 American Academy of Neurology.

Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance

NARCIS (Netherlands)

Hendriks, Yvonne M. C.; Wagner, Anja; Morreau, Hans; Menko, Fred; Stormorken, Astrid; Quehenberger, Franz; Sandkuijl, Lodewijk; Møller, Pal; Genuardi, Maurizio; van Houwelingen, Hans; Tops, Carli; van Puijenbroek, Marjo; Verkuijlen, Paul; Kenter, Gemma; van Mil, Anneke; Meijers-Heijboer, Hanne; Tan, Gita B.; Breuning, Martijn H.; Fodde, Riccardo; Wijnen, Juul Th; Bröcker-Vriends, Annette H. J. T.; Vasen, Hans

2004-01-01

BACKGROUND & AIMS: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is caused by a mutated mismatch repair (MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers. METHODS: Mutation analysis was performed in 20

Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations

NARCIS (Netherlands)

Sijmons, Rolf H.; Hofstra, Robert M. W.

Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive

[Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China].

Science.gov (United States)

2018-01-23

Hereditary colorectal cancer can be divded into two categories based on the presence or absence of polyps. The first category is characterized by the development of polyposis, which includes familial adenomatous polyposis (FAP); The second category is nonpolyposis colorectal cancer, which is represented by Lynch syndrome. "Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China" developed by the Genetics Group of the Committee of Colorectal Cancer, Chinese Anti-cancer Association, is composed of three sections, including hereditary nonpolyposis syndrome, polyposis syndrome as well as genetic evaluation of hereditary colorectal cancer. The consensus aims to provide recommendations on management of the respective hereditary syndromes in terms of definition, clinical and pathological features, diagnostic standards, treatment, and follow-ups. In addition to describing diagnostic and treatment strategies, prophylactic treatment as well as genetic screening and pedigree monitoring is highly recommended. Through the establishment of this expert consensus, we hope to promote better understanding of hereditary colorectal cancer for clinicians and encourage standardized treatment through multidisciplinery approaches, eventually improving clinical treatment and pedigree management of hereditary colorectal cancer in China.

Hereditary hemochromatosis: An opportunity for gene therapy

Directory of Open Access Journals (Sweden)

FERNANDO EZQUER

2006-01-01

Full Text Available Levels of body iron should be tightly controlled to prevent the formation of oxygen radicals, lipoperoxidation, genotoxicity, and the production of cytotoxic cytokines, which result in damage to a number of organs. Enterocytes in the intestinal villae are involved in the apical uptake of iron from the intestinal lumen; iron is further exported from the cells into the circulation. The apical divalent metal transporter-1 (DMT1 transports ferrous iron from the lumen into the cells, while the basolateral transporter ferroportin extrudes iron from the enterocytes into the circulation. Patients with hereditary hemochromatosis display an accelerated transepithelial uptake of iron, which leads to body iron accumulation that results in cirrhosis, hepatocellular carcinoma, pancreatitis, and cardiomyopathy. Hereditary hemochromatosis, a recessive genetic condition, is the most prevalent genetic disease in Caucasians, with a prevalence of one in 300 subjects. The majority of patients with hereditary hemochromatosis display mutations in the gene coding for HFE, a protein that normally acts as an inhibitor of transepithelial iron transport. We discuss the different control points in the homeostasis of iron and the different mutations that exist in patients with hereditary hemochromatosis. These control sites may be influenced by gene therapeutic approaches; one general therapy for hemochromatosis of different etiologies is the inhibition of DMT1 synthesis by antisense-generating genes, which has been shown to markedly inhibit apical iron uptake by intestinal epithelial cells. We further discuss the most promising strategies to develop gene vectors and deliver them into enterocytes

RECRUITMENT OF PATIENTS WITH HEREDITARY HAEMOCHROMATOSIS AS BLOOD DONORS

Directory of Open Access Journals (Sweden)

Marko Cukjati

2004-12-01

Full Text Available Background. Hereditary haemochromatosis is the most common inherited disorder in white persons with prevalence of about 1 in 200. Therapeutic phlebotomy is an effective treatment for the disease and prevents its sequele. In addition to their altruism, patients with hereditary haemochromatosis have also medical and monetary incentives for blood donation. Current guidelines do not allow haemochromatosis patients to donate blood. About two thirds of patients are eligible as blood donors and about two thirds of therapeutically drawn blood is suitable for transfusion. Therapeutically drawn blood could increase the blood supply by 1.5 to 30%.Conclusions. The number of states that already accept patients with hereditary haemochromatosis as blood donors is increasing. To avoid monetary incentives they offer free phlebotomies for all patients with hereditary haemochromatosis. There have been no reports about higher incidence of transfusion reactions. In Slovenia the number of therapeutic phlebotomy is increasing. We should evaluate the possibilities for recruitment of haemochromatosis patients as blood donors also in our country. It is necessary to modify regulatory restrictions and to ensure that there is no other incentives than altruism for blood donation.

Genetics and ionizing radiations. 1. Genetics and hereditary diseases

International Nuclear Information System (INIS)

Dutrillaux, B.

1980-01-01

The desoxyribonucleic acid (DNA) is the chemical vehicle of heredity. Each hereditary character is determined by a short segment of the DNA molecule called gene. Gene operations are governed by regulating systems. The DNA is located in the chromosomes, easily analysed by light microscopy. The chromosome number and form are fairly characteristic of a species. Ours has 46 chromosomes, i.e. 23 pairs. Anomalies of the hereditary stock can be qualitative: affecting one gene they are expressed by diversely serious diseases. They can be quantitative and bear on the lack or excess of a chromosome or a segment of chromosome; most often, resulting diseases are very serious; Downs's syndrome is a well-known example. The various modes of transmission of these hereditary characters are analysed. The change of a chromosome or a gene from a normal to an abnormal form is called a mutation. It occurs scarcely, but the effects of mutations accumulate. At birth, nearly 10% of children should have one abnormal hereditary character at least, however most of these characters do not induce a true disease. Anomalies are more frequent at conception, many abnormal embryos or foetuses being aliminated by miscarriages [fr

Prevalence of hereditary nonpolyposis colorectal cancer in patients with colorectal cancer in Iran: a systematic review

Directory of Open Access Journals (Sweden)

Abbas Esmaeilzadeh

2016-07-01

Full Text Available Introduction: Colorectal cancer (CRC is the third leading cause of cancer deaths in the world, and hereditary factors and family history are responsible for the incidence and development of the disease in 20 to 30% of cases. Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC, is the most common hereditary form of CRC that is inherited in an autosomal dominant manner. This study consisted of a systematic literature review of research articles that described the prevalence of HNPCC in Iranian patients with CRC. Methods: A systematic literature search was conducted in the PubMed, Scopus, IranMedex, and Google Scholar databases to identify relevant articles that describe HNPCC or Lynch syndrome in patients with CRC in Iran. For this purpose, a keyword search of the following terms was employed: (((Hereditary nonpolyposis colorectal cancer OR HNPCC OR Lynch syndrome AND (colorectal cancer OR familial colorectal cancer OR colon cancer OR rectal cancer OR bowel cancer AND IRAN. All eligible documents were collected, and the desired data were qualitatively analyzed.Result: Of the 67 articles that were found via the initial database search, only 12 were deemed to be of relevance to the current study. These articles included a total population of 3237 and this sample was selected and qualitatively analyzed. The findings of the review revealed that the frequency of mutation in MLH1, MSH2, PMS2, and MSH6 genes varied between 23.1% and 62.5% among the studied families. This indicated that HNPCC is linked with up to 5.5% of the total cases of colorectal cancers in Iran.Conclusion: The results of this study revealed that the hereditary form of HNPCC or Lynch syndrome is significantly high among patients with CRC in Iran

[Hereditary sensory and autonomic neuropathy type II A: early neurological and skeletal findings].

Science.gov (United States)

Esmer, C; Díaz Zambrano, S; Santos Díaz, M A; González Huerta, L M; Cuevas Covarrubias, S A; Bravo Oro, A

2014-04-01

The hereditary sensory and autonomic neuropathies are genetic disorders characterized by the loss of sensation including pain, tactile and temperature. Its clinical and molecular features vary widely; the symptoms may begin from birth or be noticed in the first or second decade, with different types of complications of trauma to the extremities such as ulcers, mutilations and acral amputations. They are classified into six groups from I to VI, determined by the abnormality in eleven genes leading to phenotypic variations in the age of onset and the presence or absence of dysautonomia signs. With the exception of type I, all are autosomal recessive. The type II of these neuropathies is characterized by insensitivity to pain, heat and proprioception. We describe three members of a Mexican family with WNK1 gene mutation that caused hereditary neuropathy IIA. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Hereditary spastic paraplegia with cerebellar ataxia

DEFF Research Database (Denmark)

Nielsen, J E; Johnsen, B; Koefoed, P

2004-01-01

Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria......, unipolar depression, epilepsy, migraine, and cognitive impairment was investigated. Genetic linkage analysis and sequencing of the SPG4 gene was performed and electrophysiologic investigations were carried out in six individuals and positron emission tomography (PET) in one patient. The disease was linked...... in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance...

Congenital and hereditary causes of sudden cardiac death in young adults: diagnosis, differential diagnosis, and risk stratification.

Science.gov (United States)

Stojanovska, Jadranka; Garg, Anubhav; Patel, Smita; Melville, David M; Kazerooni, Ella A; Mueller, Gisela C

2013-01-01

Sudden cardiac death is defined as death from unexpected circulatory arrest-usually a result of cardiac arrhythmia-that occurs within 1 hour of the onset of symptoms. Proper and timely identification of individuals at risk for sudden cardiac death and the diagnosis of its predisposing conditions are vital. A careful history and physical examination, in addition to electrocardiography and cardiac imaging, are essential to identify conditions associated with sudden cardiac death. Among young adults (18-35 years), sudden cardiac death most commonly results from a previously undiagnosed congenital or hereditary condition, such as coronary artery anomalies and inherited cardiomyopathies (eg, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy [ARVC], dilated cardiomyopathy, and noncompaction cardiomyopathy). Overall, the most common causes of sudden cardiac death in young adults are, in descending order of frequency, hypertrophic cardiomyopathy, coronary artery anomalies with an interarterial or intramural course, and ARVC. Often, sudden cardiac death is precipitated by ventricular tachycardia or fibrillation and may be prevented with an implantable cardioverter defibrillator (ICD). Risk stratification to determine the need for an ICD is challenging and involves imaging, particularly echocardiography and cardiac magnetic resonance (MR) imaging. Coronary artery anomalies, a diverse group of congenital disorders with a variable manifestation, may be depicted at coronary computed tomographic angiography or MR angiography. A thorough understanding of clinical risk stratification, imaging features, and complementary diagnostic tools for the evaluation of cardiac disorders that may lead to sudden cardiac death is essential to effectively use imaging to guide diagnosis and therapy.

Hereditary spastic paraplegias: membrane traffic and the motor pathway.

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Blackstone, Craig; O'Kane, Cahir J; Reid, Evan

2011-01-01

Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent work aimed at elucidating the molecular cell biology underlying the HSPs has revealed the importance of basic cellular processes — especially membrane trafficking and organelle morphogenesis and distribution— in axonal maintenance and degeneration.

Hereditary hemochromatosis

Directory of Open Access Journals (Sweden)

Stephen A. Geller

2015-03-01

Full Text Available Hereditary hemochromatosis (HH is the most commonly identified autosomal recessive genetic disorder in the white population, characterized by increased intestinal iron absorption and secondary abnormal accumulation in parenchymal organs, not infrequently accompanied by functional impairment. This entity is associated with mutations of the HFE gene (located on the short arm of chromosome 6 at location 6p22.2; closely linked to the HLA-A3 locus, which encodes the HFE protein, a membrane protein thought to regulate iron absorption by affecting the interaction between transferrin receptor and transferrin.

Genetics of hereditary neurological disorders in children.

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Huang, Yue; Yu, Sui; Wu, Zhanhe; Tang, Beisha

2014-04-01

Hereditary neurological disorders (HNDs) are relatively common in children compared to those occurring in adulthood. Recognising clinical manifestations of HNDs is important for the selection of genetic testing, genetic testing results interpretation, and genetic consultation. Meanwhile, advances in next generation sequencing (NGS) technologies have significantly enabled the discovery of genetic causes of HNDs and also challenge paediatricians on applying genetic investigation. Combination of both clinical information and advanced technologies will enhance the genetic test yields in clinical setting. This review summarises the clinical presentations as well as genetic causes of paediatric neurological disorders in four major areas including movement disorders, neuropsychiatric disorders, neuron peripheral disorders and epilepsy. The aim of this review is to help paediatric neurologists not only to see the clinical features but also the complex genetic aspect of HNDs in order to utilise genetic investigation confidently in their clinical practice. A smooth transition from research based to clinical use of comprehensive genetic testing in HNDs in children could be foreseen in the near future while genetic testing, genetic counselling and genetic data interpretation are in place appropriately.

Novel mutation in the replication focus targeting sequence domain of DNMT1 causes hereditary sensory and autonomic neuropathy IE.

Science.gov (United States)

Yuan, Junhui; Higuchi, Yujiro; Nagado, Tatsui; Nozuma, Satoshi; Nakamura, Tomonori; Matsuura, Eiji; Hashiguchi, Akihiro; Sakiyama, Yusuke; Yoshimura, Akiko; Takashima, Hiroshi

2013-03-01

DNMT1, encoding DNA methyltransferase 1 (Dnmt1), is a critical enzyme which is mainly responsible for conversion of unmethylated DNA into hemimethylated DNA. To date, two phenotypes produced by DNMT1 mutations have been reported, including hereditary sensory and autonomic neuropathy (HSAN) type IE with mutations in exon 20, and autosomal dominant cerebellar ataxia, deafness, and narcolepsy caused by mutations in exon 21. We report a sporadic case in a Japanese patient with loss of pain and vibration sense, chronic osteomyelitis, autonomic system dysfunctions, hearing loss, and mild dementia, but without definite cerebellar ataxia. Electrophysiological studies revealed absent sensory nerve action potential with nearly normal motor nerve conduction studies. Brain magnetic resonance imaging revealed mild diffuse cerebral and cerebellar atrophy. Using a next-generation sequencing system, 16 candidate genes were analyzed and a novel missense mutation, c.1706A>G (p.His569Arg), was identified in exon 21 of DNMT1. Our findings suggest that mutation in exon 21 of DNMT1 may also produce a HSAN phenotype. Because all reported mutations of DNMT1 are concentrated in exons 20 and 21, which encode the replication focus targeting sequence (RFTS) domain of Dnmt1, the RFTS domain could be a mutation hot spot. © 2013 Peripheral Nerve Society.

Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age : implications for surveillance

NARCIS (Netherlands)

van Spaendonck-Zwarts, Karin Y.; Badeloe, Sadhanna; Oosting, Sjoukje F.; Hovenga, Sjoerd; Semmelink, Harry J. F.; van Moorselaar, R. Jeroen A.; van Waesberghe, Jan Hein; Mensenkamp, Arjen R.; Menko, Fred H.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation

Genetic Causes of Rickets

Science.gov (United States)

Acar, Sezer; Demir, Korcan; Shi, Yufei

2017-01-01

Rickets is a metabolic bone disease that develops as a result of inadequate mineralization of growing bone due to disruption of calcium, phosphorus and/or vitamin D metabolism. Nutritional rickets remains a significant child health problem in developing countries. In addition, several rare genetic causes of rickets have also been described, which can be divided into two groups. The first group consists of genetic disorders of vitamin D biosynthesis and action, such as vitamin D-dependent rickets type 1A (VDDR1A), vitamin D-dependent rickets type 1B (VDDR1B), vitamin D-dependent rickets type 2A (VDDR2A), and vitamin D-dependent rickets type 2B (VDDR2B). The second group involves genetic disorders of excessive renal phosphate loss (hereditary hypophosphatemic rickets) due to impairment in renal tubular phosphate reabsorption as a result of FGF23-related or FGF23-independent causes. In this review, we focus on clinical, laboratory and genetic characteristics of various types of hereditary rickets as well as differential diagnosis and treatment approaches. PMID:29280738

Advances and challenges in hereditary cancer pharmacogenetics.

Science.gov (United States)

Cascorbi, Ingolf; Werk, Anneke Nina

2017-01-01

Cancer pharmacogenetics usually considers tumor-specific targets. However, hereditary genetic variants may interfere with the pharmacokinetics of antimetabolites and other anti-cancer drugs, which may lead to severe adverse events. Areas covered: Here, the impact of hereditary genes considered in drug labels such as thiopurine S-methyltransferase (TPMT), UDP-glucuronosyltransferase 1A1 (UTG1A1) and dihydropyrimidine dehydrogenase (DPYD) are discussed with respect to guidelines of the Clinical Pharmacogenetics Implementation Consortium (CPIC). Moreover, the association between genetic variants of drug transporters with the clinical outcome is comprehensively discussed. Expert opinion: Precision therapy in the field of oncology is developing tremendously. There are a number of somatic tumor genetic markers that are indicative for treatment with anti-cancer drugs. By contrast, for some hereditary variants, recommendations have been developed. Although we have vast knowledge on the association between drug transporter variants and clinical outcome, the overall data is inconsistent and the predictability of the related phenotype is low. Further developments in research may lead to the discovery of rare, but functionally relevant single nucleotide polymorphisms and a better understanding of multiple genomic, epigenomic as well as phenotypic factors, contributing to drug response in malignancies.

Safety and Usage of C1-Inhibitor in Hereditary Angioedema

DEFF Research Database (Denmark)

Riedl, Marc A; Bygum, Anette; Lumry, William

2016-01-01

, international patient registry documented widespread implementation of pnfC1-INH self-administration outside of a health care setting consistent with current HAE guidelines. These real-world data revealed pnfC1-INH usage for a variety of reasons in patients with HAE and showed a high level of safety regardless...... of this study was to describe safety and usage patterns of pnfC1-INH. METHODS: A multicenter, observational, registry was conducted between 2010 and 2014 at 30 United States and 7 European sites to obtain both prospective (occurring after enrollment) and retrospective (occurring before enrollment) safety...... and usage data on subjects receiving pnfC1-INH for any reason. RESULTS: Of 343 enrolled patients, 318 received 1 or more doses of pnfC1-INH for HAE attacks (11,848 infusions) or for prophylaxis (3142 infusions), comprising the safety population. Median dosages per infusion were 10.8 IU/kg (attack treatment...

Hereditary onchyo-osteo-arthrodysplasia (nail-patella syndrome) with progressive renal failure

International Nuclear Information System (INIS)

Stellamor, K.; Anzboeck, W.

1989-01-01

A case of a fully developed hereditary onycho-osteo-arthrodysplasia (nail-patella syndrome) is presented. The typical signs, such as the iliac horns or variations of the knees, cubitals and nails should be familiar to every radiologist. The associated nephropathy seems to be caused by typical changes in the glomerular basement membrane seen in electron microscopy. Asymptomatic proteinuria is found in about 60% of the cases, in 5,5-8% the disease leads to the necessity of haemodialysis because of renal insufficiency. Hence, early diagnosis is very important. (orig.) [de

Hereditary motor and sensory neuropathy Lom type in a Serbian family.

Science.gov (United States)

Dacković, J; Keckarević-Marković, M; Komazec, Z; Rakocević-Stojanović, V; Lavrnić, D; Stević, Z; Ribarić, K; Romac, S; Apostolski, S

2008-10-01

Hereditary motor and sensory neuropathy Lom type (HMSNL), also called CMT 4D, a hereditary autosomal recessive neuropathy, caused by mutation in N-Myc downstream regulated gene 1 (NDRG1 gene), was first described in a Bulgarian Gypsy population near Lom and later has been found in Gypsy communities in Italy, Spain, Slovenia and Hungary. We present two siblings with HMSNL, female and male, aged 30 and 26, respectively in a Serbian non-consanguineous family of Gypsy ethnic origin. They had normal developmental milestones. Both had symptoms of lower limb muscle weakness and walking difficulties with frequent falls, which began at the age of seven. At the age of 12, they developed hearing problems and at the age of 15 hand muscle weakness. Neurological examination revealed sensorineural hearing loss, dysarthria, severe distal and mild proximal muscle wasting and weakness, areflexia and impairment of all sensory modalities of distal distribution. Electrophysiological study revealed denervation with severe and early axonal loss. Sensorineural hearing loss was confirmed on electrocochleography and brainstem evoked potentials. Molecular genetic testing confirmed homozygote C564t (R148X) mutation in NDRG1 gene.

Genetics Home Reference: hereditary hypophosphatemic rickets

Science.gov (United States)

... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. ... families, hereditary hypophosphatemic rickets has had an autosomal dominant inheritance pattern, which means one copy of an ...

Hereditary History Preserving Bisimilarity Is Undecidable

DEFF Research Database (Denmark)

Jurdzinski, Marcin; Nielsen, Mogens

2000-01-01

History preserving bisimilarity (hp-bisimilarity) and hereditary history preserving bisimilarity (hhp-bisimilarity) are behavioural equivalences taking into account causal relationships between events of concurrent systems. Their prominent feature is being preserved under action refinement...

Management of women at high risk of hereditary breast cancer in the Veneto Regional Program for Prevention.

Science.gov (United States)

Del Sole, Annamaria; Cinquetti, Sandro; Fedato, Chiara; Montagna, Marco; Russo, Francesca; Sbrogiò, Luca Gino; Zorzi, Manuel

2015-01-01

Today it is well-known that high risk of genetic breast cancer concerns a very limited part of the population: no more than 2-3 women are affected every thousand and this condition as a whole accounts for no more than 3%-5% of all breast cancers. Following the directions contained in the 2014-2018 National Prevention Plan, Veneto's 2014-2018 Regional Program of Prevention (PRP), approved by Regional Council Resolution (DGR) No. 749 of 14.5.2015, consolidation of a pathway of diagnosis, observation, and prophylaxis for women at high risk of hereditary breast carcinoma is thus proposed. The principal activities of this policy will be the following: creation of a regional working group, survey of currently existing pathways for the identification of women at risk of hereditary breast cancer and adoption of the same, approval and consolidation of a structured regional pathway for women at high risk of hereditary breast and/or ovarian cancer, from paths of oncogenetic consultation and genetic testing to management of disease risk. Subsequent to the recognition of the pathway of diagnosis, observation, and prophylaxis for women at high risk of hereditary breast carcinoma, the Veneto region undertakes to develop a co-ordinated program of information and training on this pathway directed at the population and healthcare workers. It is firmly hoped that with the inclusion of a program for the management of women at high risk of hereditary breast cancer within the Veneto PRP this topic may become more defined and structured in terms of sustainability, integration with the existing regional networks (mammography network, Breast Unit), contrasting inequality, monitoring and evaluation, in this way pursuing the objectives of a reduction of cause-specific mortality and improvement of quality of life.

Hereditary cancer genes are highly susceptible to splicing mutations

Science.gov (United States)

Soemedi, Rachel; Maguire, Samantha; Murray, Michael F.; Monaghan, Sean F.

2018-01-01

Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations mapping to the canonical 5′ and 3′ splice sites. However, splicing mutations present in exons and deeper intronic positions are vastly underreported. A recent re-analysis of coding mutations in exon 10 of the Lynch Syndrome gene, MLH1, revealed an extremely high rate (77%) of mutations that lead to defective splicing. This finding is confirmed by extending the sampling to five other exons in the MLH1 gene. Further analysis suggests a more general phenomenon of defective splicing driving Lynch Syndrome. Of the 36 mutations tested, 11 disrupted splicing. Furthermore, analyzing past reports suggest that MLH1 mutations in canonical splice sites also occupy a much higher fraction (36%) of total mutations than expected. When performing a comprehensive analysis of splicing mutations in human disease genes, we found that three main causal genes of Lynch Syndrome, MLH1, MSH2, and PMS2, belonged to a class of 86 disease genes which are enriched for splicing mutations. Other cancer genes were also enriched in the 86 susceptible genes. The enrichment of splicing mutations in hereditary cancers strongly argues for additional priority in interpreting clinical sequencing data in relation to cancer and splicing. PMID:29505604

Hereditary cancer genes are highly susceptible to splicing mutations.

Directory of Open Access Journals (Sweden)

Christy L Rhine

2018-03-01

Full Text Available Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% of all hereditary disease alleles are classified as splicing mutations mapping to the canonical 5' and 3' splice sites. However, splicing mutations present in exons and deeper intronic positions are vastly underreported. A recent re-analysis of coding mutations in exon 10 of the Lynch Syndrome gene, MLH1, revealed an extremely high rate (77% of mutations that lead to defective splicing. This finding is confirmed by extending the sampling to five other exons in the MLH1 gene. Further analysis suggests a more general phenomenon of defective splicing driving Lynch Syndrome. Of the 36 mutations tested, 11 disrupted splicing. Furthermore, analyzing past reports suggest that MLH1 mutations in canonical splice sites also occupy a much higher fraction (36% of total mutations than expected. When performing a comprehensive analysis of splicing mutations in human disease genes, we found that three main causal genes of Lynch Syndrome, MLH1, MSH2, and PMS2, belonged to a class of 86 disease genes which are enriched for splicing mutations. Other cancer genes were also enriched in the 86 susceptible genes. The enrichment of splicing mutations in hereditary cancers strongly argues for additional priority in interpreting clinical sequencing data in relation to cancer and splicing.

New forms of -compactness with respect to hereditary classes

Directory of Open Access Journals (Sweden)

Abdo Mohammed Qahis

2019-01-01

Full Text Available A hereditary class on a set X is a nonempty collection of subsets closed under heredity. The aim of this paper is to introduce and study strong forms of u-compactness in generalized topological spaces with respect to a hereditary class, called  SuH-compactness and S- SuH-compactness. Also several of their properties are presented. Finally some eects of various kinds of functions on them are studied.

Analysis of Genetic Mutations in a Cohort of Hereditary Optic Neuropathy in Shanghai, China.

Science.gov (United States)

Gan, Dekang; Li, Mengwei; Wu, Jihong; Sun, Xinghuai; Tian, Guohong

2017-01-01

To evaluate the clinical classification and characteristics of hereditary optic neuropathy patients in a single center in China. Retrospective case study. Patients diagnosed with hereditary optic neuropathy between January 2014 and December 2015 in the neuro-ophthalmology division in Shanghai Eye and ENT Hospital of Fudan University were recruited. Clinical features as well as visual field, brain/orbital MRI, and spectrum domain optical coherence tomography (SD-OCT) were analyzed. Eighty-two patients diagnosed by gene test were evaluated, including 66 males and 16 females. The mean age of the patients was 19.4 years (range, 5-46 years). A total of 158 eyes were analyzed, including 6 unilateral, 61 bilateral, and 15 sequential. The median duration of the disease was 0.5 year (range, 0.1-20 years). Genetic test identified 68 patients with Leber hereditary optic neuropathy, 9 with dominant optic neuropathy, and 2 with a Wolfram gene mutation. There was also one case of hereditary spastic paraplegia, spinocerebellar ataxia, and polymicrogyria with optic nerve atrophy, respectively. Leber hereditary optic neuropathy is the most common detected type of hereditary optic neuropathy in Shanghai, China. The detection of other autosomal mutations in hereditary optic neuropathy is limited by the currently available technique.

Clinical features of Hereditary Haemorrhagic Telangiectasia

NARCIS (Netherlands)

Hosman, A.E.

2017-01-01

Hereditary Haemorrhagic Telangiectasia (HHT), also known as Rendu-Osler-Weber disease (ROW), is an autosomal dominant disease with multi-systemic vascular dysplasia characterized by mucocutaneous telangiectasia, arteriovenous malformations and recurrent spontaneous epistaxis (nosebleeds). Most cases

Android Mobile Informatics Application for some Hereditary Diseases and Disorders (AMAHD: A complementary framework for medical practitioners and patients

Directory of Open Access Journals (Sweden)

Olugbenga Oluwagbemi

Full Text Available Hereditary diseases and disorders constitute a public health problem. Many people in rural communities of developing countries of the world are particularly ignorant about the cause, modes of transmissions and the treatment plans for such diseases. In some cases, some people lack essential knowledge between common and rare hereditary diseases.It is therefore appropriate and essential to develop a mobile application that will act as an educative resource and a good knowledge base for common and rare hereditary diseases.The aim of this research is to develop AMAHD (Android Mobile Informatics Application for some Hereditary Diseases and Disorders.The objectives of this research are to create an android mobile application that will act as a reference point and provide useful information about various hereditary diseases to medical personnel and professionals; provide additional educational resource to biological and bioinformatics researchers in different higher institutions; and provide a pedagogical, diagnostic and complementary foundational learning tool for African research students in biosciences, bioinformatics, and all other categories of students that currently engage in multidisciplinary research in the aspect of hereditary diseases.Essential data was sourced from relevant literature. We developed AMAHD through an integration of programming languages in Java and XML (Extended Markup Language. SQLite was used to implement the database. We developed a Logical Disjunction Rule-based Algorithm (LDRA for the AMAHD’s diagnosis module.A comparative analysis between existing commercial hereditary mobile applications and AMAHD was conducted and the results presented. A world-wide online survey (spanning Africa, Asia, Europe, America and Australia was conducted to sample the opinion of individuals across the globe on the classification of hereditary diseases as either rare or common, within their respective regions. In addition, an evaluation of

Genetics Home Reference: hereditary hemochromatosis

Science.gov (United States)

... Type 1 hemochromatosis results from mutations in the HFE gene, and type 2 hemochromatosis results from mutations in ... about the genes associated with hereditary hemochromatosis HAMP HFE HJV PNPLA3 SLC40A1 TFR2 Related Information What is a gene? What is a gene mutation and how do ...

Interdisciplinary management for restoration of function and esthetics in a patient with hereditary amelogenesis imperfecta

Directory of Open Access Journals (Sweden)

Sushma Dhiman

2015-01-01

Full Text Available Amelogenesis imperfecta (AI is a type of the hereditary disorder which is expressed as a group of conditions causing developmental alterations in the structure of enamel. It is associated with a reduction of oral health-related quality-of-life, has an impact on psychological well-being, and leads to various physiological problems. Children or adults with AI express varying degree of malocclusions either in the form of crowding, impacted teeth, spacing, retained teeth, reduced vertical height due to abnormal tooth structure or undue tooth loss. Orthodontic treatment should precede esthetic rehabilitation. Proper diagnosis of the case is quintessential to provide durable functional and esthetic result to these patients, improving the quality of their lives. We present a case of interdisciplinary management for restoring function and esthetics in a patient with hereditary AI of the hypoplastic type accompanied with tooth impaction and some other dental anomalies.

Multigeneration family with dominant SPG30 hereditary spastic paraplegia.

Science.gov (United States)

Roda, Ricardo H; Schindler, Alice B; Blackstone, Craig

2017-11-01

Autosomal recessive KIF1A missense mutations cause hereditary spastic paraplegia (HSP) type SPG30, while recessive truncations lead to sensory and autonomic neuropathy (HSN2C) and many de novo missense mutations are associated with cognitive impairment. Here, we describe family members across three generations with pure HSP. A heterozygous p.Ser69Leu KIF1A mutation segregates with those afflicted. The same variant was previously reported in a Finnish father and son with pure HSP as well as four members of a Sicilian kindred with more intrafamilial phenotypic variability. This further validates the pathogenicity of the p.Ser69Leu mutation and suggests that it may represent a mutation hot spot.

The investigation on hereditary disease and congenital malformation in the surrounding area of the nuclear test site in Xinjiang

International Nuclear Information System (INIS)

Zou Wenliang; Zhang Jujing

1989-01-01

The investigation on hereditary disease and congenital malformation, on the children below eleven years old and living in the surrounding area of the nuclear test site and control area is reported. The total prevalence rate of the ninteen kinds of hereditary disease and congenital malformation in both areas are 7.12%0 and 7.28%0, respectively. The prevalence rate of congenital foolishness in investigation area is 0.64%0; while in control area, it is 0.54%0. There is no significant difference between the two areas. However, it is found that the prevalence rate of harelip in investigation area is higher than in control area, whereas the prevalence rate of congenital heart disease in control area is higher than in investigation area. As for the rests there is no significant difference. There is no significant difference between the two areas. It is concluded that nuclear tests in China did not cause hereditary disease and congenital malformation for the children who live in surrounding area, of the nuclear test site

Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: demonstration of a founder mutation in the Turkish population.

Science.gov (United States)

Tüysüz, Beyhan; Bayrakli, Fatih; DiLuna, Michael L; Bilguvar, Kaya; Bayri, Yasar; Yalcinkaya, Cengiz; Bursali, Aysegul; Ozdamar, Elif; Korkmaz, Baris; Mason, Christopher E; Ozturk, Ali K; Lifton, Richard P; State, Matthew W; Gunel, Murat

2008-05-01

Hereditary sensory and autonomic neuropathy type IV (HSAN IV), or congenital insensitivity to pain with anhidrosis, is an autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis from deinnervated sweat glands, and delayed mental and motor development. Mutations in the neurotrophic tyrosine kinase receptor type 1 (NTRK1), a receptor in the neurotrophin signaling pathway phosphorylated in response to nerve growth factor, are associated with this disorder. We identified six families from Northern Central Turkey with HSAN IV. We screened the NTRK1 gene for mutations in these families. Microsatellite and single nucleotide polymorphism (SNP) markers on the Affymetrix 250K chip platform were used to determine the haplotypes for three families harboring the same mutation. Screening for mutations in the NTRK1 gene demonstrated one novel frameshift mutation, two novel nonsense mutations, and three unrelated kindreds with the same splice-site mutation. Genotyping of the three families with the identical splice-site mutation revealed that they share the same haplotype. This report broadens the spectrum of mutations in NTRK1 that cause HSAN IV and demonstrates a founder mutation in the Turkish population.

Repetitive Transcranial Magnetic Stimulation in Patients with Hereditary Spastic Paraplegia

Directory of Open Access Journals (Sweden)

Mehmet Ağırman

2011-06-01

Full Text Available Hereditary spastic paraplegia (HSPP is a heterogeneous genetic disease characterized by progressive spasticity of lower extremities. Spasticity is a major cause of long-term disability in HSPP and significantly affects the functional life of patients. Repetitive transcranial magnetic stimulation (rTMS is widely used in diagnosis and treatment of many neurological and psychiatric diseases. Although the positive impacts of rTMS for spasticity have been reported, no study has been found on HSPP. We present two HSPP patients treated with low frequency rTMS (20 minutes at a frequency of 1 Hz (1200 pulses, for a period of 10 treatment sessions.

Repetitive Transcranial Magnetic Stimulation in Patients with Hereditary Spastic Paraplegia

Directory of Open Access Journals (Sweden)

Mehmet Ağırman

2011-06-01

Full Text Available Hereditary spastic paraplegia (HSPP is a heterogeneous genetic disease characterized by progressive spasticity of lower extremities. Spasticity is a major cause of long-term disability in HSPP and significantly affects the functional life of patients. Repetitive transcranial magnetic stimulation (rTMS is widely used in diagnosis and treatment of many neurological and psychiatric diseases. Although the positive impacts of rTMS for spasticity have been reported, no study has been found on HSPP. We present two HSPP patients treated with low frequency rTMS (20 minutes at a frequency of 1 Hz (1200 pulses, for a period of 10 treatment sessions

PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

NARCIS (Netherlands)

van Paassen, Barbara W.; van der Kooi, Anneke J.; van Spaendonck-Zwarts, Karin Y.; Verhamme, Camiel; Baas, Frank; de Visser, Marianne

2014-01-01

PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is

Non-motor symptoms in patients with hereditary spastic paraplegia caused by SPG4 mutations.

Science.gov (United States)

Servelhere, K R; Faber, I; Saute, J A M; Moscovich, M; D'Abreu, A; Jardim, L B; Teive, H A G; Lopes-Cendes, I; Franca, M C

2016-02-01

Non-motor manifestations are frequently overlooked in degenerative disorders and little is known about their frequency and clinical relevance in SPG4 hereditary spastic paraplegia (SPG4-HSP). Thirty patients with SPG4-HSP and 30 healthy controls answered the Modified Fatigue Impact Scale, Epworth Sleepiness Scale, Brief Pain Inventory and Beck Depression Inventory. Student's t test was used to compare groups and linear regression was used to assess correlations. Patients had higher fatigue scores than controls (31.0 ± 16.5 vs. 14.5 ± 16.0, P = 0.002) as well as pain (3.4 ± 2.7 vs. 1.0 ± 1.6, P = 0.001) and depression (12.7 ± 8.9 vs. 4.4 ± 3.8, P depression and possibly with disease severity (P = 0.008 and 0.07, respectively). Fatigue, pain and depression are frequent and often severe manifestations in patients with SPG4-HSP. © 2016 EAN.

Structural annotation of Beta-1,4-N-acetyl galactosaminyltransferase 1 (B4GALNT1) causing Hereditary Spastic Paraplegia 26.

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Dad, Rubina; Malik, Uzma; Javed, Aneela; Minassian, Berge A; Hassan, Muhammad Jawad

2017-08-30

Beta-1,4-N-acetyl galactosaminyltransferase 1, B4GALNT1, is a GM2/GD2 synthase, involved in the expression of glycosphingolipids (GSLs) containing sialic acid. Mutations in the gene B4GALNT1 cause Hereditary Spastic Paraplegia 26 (HSP26). In present study we have made attempt to predict the potential structural of the human B4GALNT1 protein. The results illustrated that the amino acid sequences of B4GALNT1 are not 100% conserved among selected twenty species. One signal peptide and one transmembrane domain predicted in human wild type B4GALNT1 protein with aliphatic index of 92.76 and theoretical (iso-electric point) pI of 8.93. It was a kind of unstable protein with Grand average of hydropathicity (GRAVY) of -0.127. Various post-translational modifications were also predicted to exist in B4GALNT1 and predicted to interact with different proteins including ST8SIA5, SLC33A1, GLB1 and others. In the final round, reported missense mutations have shown the further decrease in stability of the protein. This in-silico analysis of B4GALNT1 protein will provide the basis for the further studies on structural variations and biological pathways involving B4GALNT1 in the HSP26. Copyright © 2017. Published by Elsevier B.V.

Hereditary rickets. How genetic alterations explain the biochemical and clinical phenotypes.

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Papadopoulou, Anna; Gole, Evaggelia; Nicolaidou, Polyxeni

2013-12-01

The reemergence of vitamin D deficiency in the industrialized countries resurrects the "threat" of nutritional rickets, especially among pediatric populations, a fact that may lead to underdiagnosis of hereditary rickets. Today, hereditary rickets may be subdivided into two main groups according to their biochemical profile: the one associated with defects in vitamin D synthesis and action and the second associated with abnormal phosphorus metabolism. The classification of the patients in a particular group of hereditary rickets is determinative of the treatment to follow. This review, through the recent advances on vitamin D and P metabolism, discusses the molecular and biochemical defects associated to each group of inherited rickets, as well as the clinical phenotypes and the recommended therapeutic approaches.

Molecular basis of hereditary C1q deficiency-revisited: identification of several novel disease-causing mutations

DEFF Research Database (Denmark)

Schejbel, L; Skattum, L; Hagelberg, S

2011-01-01

C1q is the central pattern-recognition molecule in the classical pathway of the complement system and is known to have a key role in the crossroads between adaptive and innate immunity. Hereditary C1q deficiency is a rare genetic condition strongly associated with systemic lupus erythematosus...... and increased susceptibility to bacterial infections. However, the clinical symptoms may vary. For long, the molecular basis of C1q deficiency was ascribed to only six different mutations. In the present report, we describe five new patients with C1q deficiency, present the 12 causative mutations described till...... now and review the clinical spectrum of symptoms found in patients with C1q deficiency. With the results presented here, confirmed C1q deficiency is reported in 64 patients from at least 38 families....

Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer.

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Wells, Samuel A; Gosnell, Jessica E; Gagel, Robert F; Moley, Jeffrey; Pfister, David; Sosa, Julie A; Skinner, Michael; Krebs, Annetta; Vasselli, James; Schlumberger, Martin

2010-02-10

PURPOSE There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. METHODS Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of patients (ie, 16 of 30 patients) experienced stable disease at >/= 24 weeks, which yielded a disease control rate of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). CONCLUSION In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.

Factor XII-independent activation of the bradykinin-forming cascade

DEFF Research Database (Denmark)

Joseph, Kusumam; Tholanikunnel, Baby G; Bygum, Anette

2013-01-01

and assayed for kallikrein formation. C1-INH was removed from factor XII-deficient plasma by means of immunoadsorption. RESULTS: We demonstrate that prekallikrein-HK will activate to kallikrein in phosphate-containing buffers and that the rate is further accelerated on addition of heat shock protein 90...... the prekallikrein-HK complex to prevent HK cleavage either by prekallikrein or by prekallikrein-HK autoactivation to generate kallikrein. In patients with hereditary angioedema, kallikrein and bradykinin formation can occur without invoking factor XII activation, although the kallikrein formed can rapidly activate...

Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) caused by a VDR mutation: A novel mechanism of dominant inheritance.

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Isojima, Tsuyoshi; Ishizawa, Michiyasu; Yoshimura, Kazuko; Tamura, Mayuko; Hirose, Shinichi; Makishima, Makoto; Kitanaka, Sachiko

2015-06-01

Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is caused by mutations in the VDR gene, and its inheritance is autosomal recessive. In this report, we aimed to confirm whether HVDRR is occasionally inherited as a dominant trait. An 18-month-old Japanese boy was evaluated for short stature and bowlegs. His father had been treated for rickets during childhood, and his paternal grandfather had bowlegs. We diagnosed him with HVDRR based on laboratory data and radiographic evidence of rickets. Sequence analyses of VDR were performed, and the functional consequences of the detected mutations were analyzed for transcriptional activity, ligand binding, and interaction with the retinoid X receptor, cofactors, and the vitamin D response element (VDRE). A novel mutation (Q400LfsX7) and a reported variant (R370H) were identified in the patient. Heterozygous Q400LfsX7 was detected in his father, and heterozygous R370H was detected in his healthy mother. Functional studies revealed that the transcriptional activity of Q400LfsX7-VDR was markedly disturbed. The mutant had a dominant-negative effect on wild-type-VDR, and the ligand binding affinity of Q400LfsX7-VDR was completely impaired. Interestingly, Q400LfsX7-VDR had a strong interaction with corepressor NCoR and could interact with VDRE without the ligand. R370H-VDR was functionally similar to wild-type-VDR. In conclusion, we found a dominant-negative mutant of VDR causing dominantly inherited HVDRR through a constitutive corepressor interaction, a mechanism similar to that in dominantly inherited thyroid hormone receptor mutations. Our report together with a reported pedigree suggested a distinct inheritance of HVDRR and enriched our understanding of VDR abnormalities.

Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR caused by a VDR mutation: A novel mechanism of dominant inheritance

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Tsuyoshi Isojima

2015-06-01

Full Text Available Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR is caused by mutations in the VDR gene, and its inheritance is autosomal recessive. In this report, we aimed to confirm whether HVDRR is occasionally inherited as a dominant trait. An 18-month-old Japanese boy was evaluated for short stature and bowlegs. His father had been treated for rickets during childhood, and his paternal grandfather had bowlegs. We diagnosed him with HVDRR based on laboratory data and radiographic evidence of rickets. Sequence analyses of VDR were performed, and the functional consequences of the detected mutations were analyzed for transcriptional activity, ligand binding, and interaction with the retinoid X receptor, cofactors, and the vitamin D response element (VDRE. A novel mutation (Q400LfsX7 and a reported variant (R370H were identified in the patient. Heterozygous Q400LfsX7 was detected in his father, and heterozygous R370H was detected in his healthy mother. Functional studies revealed that the transcriptional activity of Q400LfsX7-VDR was markedly disturbed. The mutant had a dominant-negative effect on wild-type-VDR, and the ligand binding affinity of Q400LfsX7-VDR was completely impaired. Interestingly, Q400LfsX7-VDR had a strong interaction with corepressor NCoR and could interact with VDRE without the ligand. R370H-VDR was functionally similar to wild-type-VDR. In conclusion, we found a dominant-negative mutant of VDR causing dominantly inherited HVDRR through a constitutive corepressor interaction, a mechanism similar to that in dominantly inherited thyroid hormone receptor mutations. Our report together with a reported pedigree suggested a distinct inheritance of HVDRR and enriched our understanding of VDR abnormalities.

Atrofia óptica hereditaria autosómica dominante: A propósito de una familia Dominant autosomal hereditary optical atrophy: Apropos of a family

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Noel Taboada Lugo

2004-12-01

Full Text Available Entre las causas de pérdida insidiosa, bilateral y simétrica de la visión central se deben tener siempre presente las atrofias ópticas heredo degenerativas. La atrofia óptica hereditaria autosómica dominante es la forma más frecuente de atrofia óptica heredofamiliar simple o monosintomática. Se realizó la caracterización clínica de una familia con el diagnóstico de esta discapacidad visual.Among the causes of insidious, bilateral and symmetric loss of the central vision, the hereditary and degenerative optical atrophies should always be taken into account. The dominant autosomal hereditary optical atrophy is the most frequent form of simple or monosymptomatic hereditary family optical atrophy. The clinical characterization of a family with the diagnosis of this visual impairment was made.

Hereditary noetherian prime rings and idealizers

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Levy, Lawrence S

2011-01-01

The direct sum behaviour of its projective modules is a fundamental property of any ring. Hereditary Noetherian prime rings are perhaps the only noncommutative Noetherian rings for which this direct sum behaviour (for both finitely and infinitely generated projective modules) is well-understood, yet highly nontrivial. This book surveys material previously available only in the research literature. It provides a re-worked and simplified account, with improved clarity, fresh insights and many original results about finite length modules, injective modules and projective modules. It culminates in the authors' surprisingly complete structure theorem for projective modules which involves two independent additive invariants: genus and Steinitz class. Several applications demonstrate its utility. The theory, extending the well-known module theory of commutative Dedekind domains and of hereditary orders, develops via a detailed study of simple modules. This relies upon the substantial account of idealizer subrings wh...

Hereditary Ovarian Cancer: Not Only BRCA 1 and 2 Genes

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Angela Toss

2015-01-01

Full Text Available More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51, BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is relevant for the future development of molecular diagnostic strategies and targeted therapeutic approaches. The recent development and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyze multiple cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and guide treatment decision-making.

Inflammation and neuropathic attacks in hereditary brachial plexus neuropathy

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Klein, C; Dyck, P; Friedenberg, S; Burns, T; Windebank, A; Dyck, P

2002-01-01

Objective: To study the role of mechanical, infectious, and inflammatory factors inducing neuropathic attacks in hereditary brachial plexus neuropathy (HBPN), an autosomal dominant disorder characterised by attacks of pain and weakness, atrophy, and sensory alterations of the shoulder girdle and upper limb muscles. Methods: Four patients from separate kindreds with HBPN were evaluated. Upper extremity nerve biopsies were obtained during attacks from a person of each kindred. In situ hybridisation for common viruses in nerve tissue and genetic testing for a hereditary tendency to pressure palsies (HNPP; tomaculous neuropathy) were undertaken. Two patients treated with intravenous methyl prednisolone had serial clinical and electrophysiological examinations. One patient was followed prospectively through pregnancy and during the development of a stereotypic attack after elective caesarean delivery. Results: Upper extremity nerve biopsies in two patients showed prominent perivascular inflammatory infiltrates with vessel wall disruption. Nerve in situ hybridisation for viruses was negative. There were no tomaculous nerve changes. In two patients intravenous methyl prednisolone ameliorated symptoms (largely pain), but with tapering of steroid dose, signs and symptoms worsened. Elective caesarean delivery did not prevent a typical postpartum attack. Conclusions: Inflammation, probably immune, appears pathogenic for some if not all attacks of HBPN. Immune modulation may be useful in preventing or reducing the neuropathic attacks, although controlled trials are needed to establish efficacy, as correction of the mutant gene is still not possible. The genes involved in immune regulation may be candidates for causing HBPN disorders. PMID:12082044

Detection of Hereditary 1,25-Hydroxyvitamin D-Resistant Rickets Caused by Uniparental Disomy of Chromosome 12 Using Genome-Wide Single Nucleotide Polymorphism Array.

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Mayuko Tamura

Full Text Available Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR is an autosomal recessive disease caused by biallelic mutations in the vitamin D receptor (VDR gene. No patients have been reported with uniparental disomy (UPD.Using genome-wide single nucleotide polymorphism (SNP array to confirm whether HVDRR was caused by UPD of chromosome 12.A 2-year-old girl with alopecia and short stature and without any family history of consanguinity was diagnosed with HVDRR by typical laboratory data findings and clinical features of rickets. Sequence analysis of VDR was performed, and the origin of the homozygous mutation was investigated by target SNP sequencing, short tandem repeat analysis, and genome-wide SNP array.The patient had a homozygous p.Arg73Ter nonsense mutation. Her mother was heterozygous for the mutation, but her father was negative. We excluded gross deletion of the father's allele or paternal discordance. Genome-wide SNP array of the family (the patient and her parents showed complete maternal isodisomy of chromosome 12. She was successfully treated with high-dose oral calcium.This is the first report of HVDRR caused by UPD, and the third case of complete UPD of chromosome 12, in the published literature. Genome-wide SNP array was useful for detecting isodisomy and the parental origin of the allele. Comprehensive examination of the homozygous state is essential for accurate genetic counseling of recurrence risk and appropriate monitoring for other chromosome 12 related disorders. Furthermore, oral calcium therapy was effective as an initial treatment for rickets in this instance.

Molecular Analysis: Microsatellite Instability and Loss of Heterozygosity of Tumor Suppressor Gene in Hereditary Non-Polyposis Colorectal Cancer (HNPCC

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Vesna Hadžiavdić

2009-02-01

Full Text Available HNPCC (Hereditary non-polyposis colorectal cancer development is caused by mutation of genes included in system of mismatch repair genes. The mutation exists at 60% of patients in hMSH2 gene, 30% in hMLH1 and 10% both in hPMS1and hPMS2 genes. RER+ exists in about 90% in hereditary non-polyposis colorectal cancer and about 15-28% in sporadic cancers.The purpose of the study was to determine highly sensitive microsatellite markers which can be fast and efficient way of microsatellite screening for detection of HNPCC patients. Moreover, we have analysed the loss of heterozygosity of tumour suppressor genes which could have the diagnostic value in detection of HPNCC patients.

MRI in Leber's hereditary optic neuropathy

DEFF Research Database (Denmark)

Matthews, Lucy; Enzinger, Christian; Fazekas, Franz

2015-01-01

BACKGROUND: Leber's hereditary optic neuropathy (LHON) and a multiple sclerosis (MS)-like illness appear to coexist 50 times more frequently than would be expected by chance. This association of LHON and MS (LMS) raises an important question about whether there could be a common pathophysiological...

Descriptive Epidemiology, Molecular Biology and Genetics of Hereditary Prostate Cancer in Denmark

DEFF Research Database (Denmark)

Bentzon, Diem Nguyen

2012-01-01

A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer.......A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer....

Genetics 101 --The Hereditary Material of Life

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... of this page please turn Javascript on. Feature: Genetics 101 Genetics 101 — The Hereditary Material of Life Past Issues / Summer 2013 Table of Contents Genetics is the study of heredity, the process in ...

Genetic and Clinical Analyses of DOA and LHON in 304 Chinese Patients with Suspected Childhood-Onset Hereditary Optic Neuropathy.

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Yadi Li

Full Text Available Leber hereditary optic neuropathy (LHON and dominant optic atrophy (DOA, the most common forms of hereditary optic neuropathy, are easily confused, and it is difficult to distinguish one from the other in the clinic, especially in young children. The present study was designed to survey the mutation spectrum of common pathogenic genes (OPA1, OPA3 and mtDNA genes and to analyze the genotype-phenotype characteristics of Chinese patients with suspected childhood-onset hereditary optic neuropathy. Genomic DNA and clinical data were collected from 304 unrelated Chinese probands with suspected hereditary optic neuropathy with an age of onset below 14 years. Sanger sequencing was used to screen variants in the coding and adjacent regions of OPA1, OPA3 and the three primary LHON-related mutation sites in mitochondrial DNA (mtDNA (m.3460G>A, m.11778G>A and m.14484T>C. All patients underwent a complete ophthalmic examination and were compared with age-matched controls. We identified 89/304 (29.3% primary mtDNA mutations related to LHON in 304 probands, including 76 mutations at m.11778 (76/89, 85.4% of all mtDNA mutations, four at m.3460 (4/89, 4.5% and nine at m.14484 (9/89, 10.1%. This result was similar to the mutation frequency among Chinese patients with LHON of any age. Screening of OPA1 revealed 23 pathogenic variants, including 11 novel and 12 known pathogenic mutations. This study expanded the OPA1 mutation spectrum, and our results showed that OPA1 mutation is another common cause of childhood-onset hereditary optic neuropathy in Chinese pediatric patients, especially those with disease onset during preschool age.

Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis

NARCIS (Netherlands)

Vasen, H. F.; Wijnen, J. T.; Menko, F. H.; Kleibeuker, J. H.; Taal, B. G.; Griffioen, G.; Nagengast, F. M.; Meijers-Heijboer, E. H.; Bertario, L.; Varesco, L.; Bisgaard, M. L.; Mohr, J.; Fodde, R.; Khan, P. M.

1996-01-01

Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers. The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of carriers within

Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis

NARCIS (Netherlands)

Vasen, HFA; Wijnen, JT; Menko, FH; Kleibeuker, JH; Taal, BG; Griffioen, G; Nagengast, FM; MeijersHeijboer, EH; Bertario, L; Varesco, L; Bisgaard, ML; Mohr, J; Fodde, R; Khan, PM

Background & Aims: Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers, The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of

Neuromyelitis optica antibody in Leber hereditary optic neuropathy: case report

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Luciano Mesquita Simão

2012-08-01

Full Text Available Neuromyelitis optica antibody (or aquaporin-4 antibody is a well stablished serum marker associated to high-risk neuromyelitis optica syndrome that presents as an inflammatory demyelinating disease characterized by the occurrence of bilateral and simultaneous optic neuritis without complete visual recovery or it occurs as an isolated episode of transverse myelitis accompanied by longitudinally extensive spinal cord lesions. On the other hand, Leber hereditary optic neuropathy is a primarily hereditary disorder that affects all tissues of the body and its clinical presentation is tissue-specific for the optic nerve and, eventually, it might reach the spinal cord. Overlapping clinical features of neuromyelitis optica and Leber hereditary optic neuropathy may suggest common target organ diseases. The case report described herein emphasizes the coexistence of serum markers of both diseases, and suggests that further investigation of this challenging clinical presentation is warranted to confirm or rule out this association.

Identification of Two Disease-causing Genes TJP2 and GJB2 in a Chinese Family with Unconditional Autosomal Dominant Nonsyndromic Hereditary Hearing Impairment

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Hong-Yang Wang

2015-01-01

Full Text Available Background: There are more than 300 genetic loci that have been found to be related to hereditary hearing impairment (HHI, including 92 causative genes for nonsyndromic hearing loss, among which 34 genes are related to autosomal dominant nonsyndromic HHI (ADNSHHI. Traditional linkage analysis and candidate gene sequencing are not effective at detecting the ADNSHHI, especially for the unconditional families that may have more than one pathogenic cause. This study identified two disease-causing genes TJP2 and GJB2 in a Chinese family with unconditional ADNSHHI. Methods: To decipher the genetic code of a Chinese family (family 686 with ADNSHHI, different gene screening techniques have been performed, including linkage analysis, candidate genes screening, high-throughput sequencing and Sanger sequencing. These techniques were done on samples obtained from this family over a period of 10 years. Results: We identified a pathogenic missense mutation, c. 2081G>A (p.G694E, in TJP2, a gene that plays a crucial role in apoptosis and age-related hearing loss (ARHL. The mutation was co-segregated in this pedigree in all, but not in the two patients who presented with different phenotypes from the other affected family members. In one of the two patients, we confirmed that the compound heterozygosity for p.Y136FNx01 and p.G45E in the GJB2 gene may account for the phenotype shown in this patient. Conclusions: We identified the co-occurrence of two genetic causes in family 686. The possible disease-causing missense mutation of TJP2 in family 686 presents an opportunity for further investigation into ARHL. It is necessary to combine various genes screening methods, especially for some unconventional cases.

Hereditary sensory neuropathy type I

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Auer-Grumbach Michaela

2008-03-01

Full Text Available Abstract Hereditary sensory neuropathy type I (HSN I is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7 identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN, especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra

Hereditary sensory neuropathy type I.

Science.gov (United States)

Auer-Grumbach, Michaela

2008-03-18

Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin

Hereditary pancreatitis: current perspectives

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Raphael KL

2016-07-01

Full Text Available Kara L Raphael, Field F Willingham Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA Abstract: Hereditary pancreatitis (HP is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy. Keywords: pancreatic cancer, chronic pancreatitis, idiopathic pancreatitis, pancreatitis, familial pancreatitis, genetic mutations

Hereditary and microbiological factors influencing the airway immunological profile of neonates

DEFF Research Database (Denmark)

Følsgaard, Nilofar

2012-01-01

is well-recognized, with estimated heritability as high as 60% in asthma. Atopic hereditary disease linkage in the offspring seems stronger for maternal than paternal atopic disease. But it is not known how parental atopic disease may affect early immunity in the target organ, the airways. COPSAC has...... mucosa. There was no paternal linkage to the mucosal immune response pattern, suggesting maternal programming of the fetus or neonate is causing an aberrant local airway immune profile in the newborn child. Furthermore our results suggest an association between maternal atopic disease and the expression...... recently reported an association between abnormal bacterial colonization with M. catarrhalis, S. pneumoniae, H. influenzae of the upper airways of neonates and later development of asthma. This led to the hypothesis that the interaction between genetics and this microbiome in very early life may cause...

The tumour spectrum in hereditary non-polyposis colorectal cancer: a study of 24 kindreds in the Netherlands

NARCIS (Netherlands)

Vasen, H. F.; Offerhaus, G. J.; den Hartog Jager, F. C.; Menko, F. H.; Nagengast, F. M.; Griffioen, G.; van Hogezand, R. B.; Heintz, A. P.

1990-01-01

The hereditary colonic cancer syndrome without polyposis, hereditary non-polyposis colorectal cancer (HNPCC), is usually divided into 2 main categories: hereditary site-specific colorectal cancer (Lynch syndrome I) and colorectal cancer in association with other forms of cancer (Lynch syndrome II).

The prevalence of primary hereditary hemochromatosis in central Anatolia.

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Karaca, Halit; Güven, Kadri; Önal, Müge; Gürsoy, Şebnem; Başkol, Mevlüt; Özkul, Yusuf

2013-01-01

Hereditary hemochromatosis is an autosomal recessive disorder associated with the HFE genes. Early identification and diagnosis is important as end stage organ damage may occur if treatment is delayed.. This study aimed to identify the prevalence of hereditary hemochromatosis in Kayseri and surroundings known as Central Anatolia. 2304 participants (1220 males, 1084 females) who were older then the age of 17 were included in the study conducted between December 2005 and December 2006 in Kayseri, Turkey. Transferin saturation was measured from overnight fasting blood samples. Serum iron, total iron binding capacity, and transferin saturation were measured. Serum ferritin levels and hereditary hemochromatosis genetic analysis were also performed after an overnight fasting blood samples from participants whose transferin saturation results were more than 50% in man and more than 45% in women. The homozygote C282Y mutation and heterozygote C282Y mutation prevalences were found as 0.08% (1/1220) and 0.08% (1/1220) in male participants, respectively. The heterozygote H63D mutation prevalence was found in 0.09% (1/1084) of female participants. Calculated prevalences in general population are as follows; The homozygote C282Y mutation prevalence is 0.043% (1/2304), the heterozygote C282Y mutation prevalence is 0.043% (1/2304) and the heterozygote H63D mutation prevalence is 0.043% (1/2304). The prevalence of hereditary hemochromatosis in Central Anatolia is 0.043% (1/2304). Because of the relatively low frequency, population screening studies are not cost-effective.

Intragenic Duplication A Novel Mutational Mechanism in Hereditary Pancreatitis

DEFF Research Database (Denmark)

Joergensen, M. T.; Geisz, A.; Brusgaard, K.

2011-01-01

OBJECTIVES: In a hereditary pancreatitis family from Denmark, we identified a novel intragenic duplication of 9 nucleotides in exon-2 of the human cationic trypsinogen (PRSS1) gene (c.63_71dup) which at the amino-acid level resulted in the insertion of 3 amino acids within the activation peptide...... pancreatitis. The accelerated activation of p.K23_I24insIDK by cathepsin B is a unique biochemical property not found in any other pancreatitis-associated trypsinogen mutant. In contrast, the robust autoactivation of the novel mutant confirms the notion that increased autoactivation is a disease......-relevant mechanism in hereditary pancreatitis....

Dysphonia and vocal fold telangiectasia in hereditary hemorrhagic telangiectasia.

Science.gov (United States)

Chang, Joseph; Yung, Katherine C

2014-11-01

This case report is the first documentation of dysphonia and vocal fold telangiectasia as a complication of hereditary hemorrhagic telangiectasia (HHT). Case report of a 40-year-old man with HHT presenting with 2 years of worsening hoarseness. Hoarseness corresponded with a period of anticoagulation. Endoscopy revealed vocal fold scarring, vocal fold telangiectasias, and plica ventricular is suggestive of previous submucosal vocal fold hemorrhage and subsequent counterproductive compensation with ventricular phonation. Hereditary hemorrhagic telangiectasia may present as dysphonia with vocal fold telangiectasias and place patients at risk of vocal fold hemorrhage. © The Author(s) 2014.

Leber's Hereditary Optic Neuropathy: A Case Report

Directory of Open Access Journals (Sweden)

Chi-Wu Chang

2003-10-01

Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited mitochondrial disease that primarily affects the optic nerve, causing bilateral vision loss in juveniles and young adults. A 12-year-old boy had complained of blurred vision in both eyes for more than 1 year. His best-corrected visual acuity was 0.08 in the right eye and 0.1 in the left. Ophthalmologic examination showed bilateral optic disc hyperemia and margin blurring, peripapillary telangiectasis, and a relative afferent pupil defect in his right eye. Fluorescein angiography showed no stain or leakage around the optic disc in the late phase. Visual field analysis showed central scotoma in the left eye and a near-total defect in the right. Upon examination of the patient's mitochondrial DNA, a point mutation at nucleotide position 11778 was found, and the diagnosis of LHON was confirmed. Coenzyme Q10 was used to treat the patient.

Hereditary breast and ovarian cancer

DEFF Research Database (Denmark)

Nielsen, Finn Cilius; Hansen, Thomas van Overeem; Sørensen, Claus Storgaard

2016-01-01

Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among...... of putative causal variants and the clinical application of new HBOC genes in cancer risk management and treatment decision-making....

Major and minor form of hereditary hyperekplexia

NARCIS (Netherlands)

Tijssen, MAJ; Vergouwe, MN; van Dijk, JG; Rees, M; Frants, RR; Brown, P

Hyperekplexia is a hereditary neurological disorder characterized by excessive startle responses. Within the disorder two clinical forms can be distinguished. The major form is characterized by continuous generalized stiffness in the first year of life and an exaggerated startle reflex, accompanied

Health-related quality of life in Danish children with hereditary angioedema

DEFF Research Database (Denmark)

Aabom, Anne; Nguyen, Dan; Fisker, Niels

2017-01-01

have considerable impact on the health-related quality of life (HRQoL) in adult patients. Half the patients with C1-INH-HAE develop symptoms before the age of 10 years. However, the HRQoL in children with C1-INH-HAE is almost unexplored. Objective: To investigate HRQoL in Danish children with C1...... were the PedsQL (Child Self-Report and Parent Proxy-Report forms); the Children's Dermatology Life Quality Index; a nonvalidated, diseasespecific quality-of-life questionnaire; and two visual analog scales that rated general health. Results: The HRQoL scores in our study were comparable with the normal...... the Parent Proxy-Report form carried the disease. Conclusion: Overall, the children assessed on average had a normal HRQoL and better than those with other common skin disorders. However, according to our findings, health care providers should be especially attentive to HRQoL when children with C1-INH...

Activation of the ficolin-lectin pathway during attacks of hereditary angioedema

DEFF Research Database (Denmark)

Csuka, Dorottya; Munthe-Fog, Lea; Hein, Estrid

2014-01-01

enrolled. We analyzed blood samples drawn during attacks, and obtained 35 samples from the same patients during symptom-free periods. The serum levels of ficolin-2, ficolin-3, MASP-2, ficolin-3/MASP-2 complex, C1-INH, and C4, as well as the extent of ficolin-3-mediated terminal complement complex (FCN3-TCC......) deposition, were measured using ELISA-based methods. RESULTS: Levels of MASP-2 and of the ficolin-3/MASP-2 complex were elevated (P TCC was lower (P TCC...

The role of Clinical Geneticists in Hereditary Cancer Management and Research

Directory of Open Access Journals (Sweden)

Hanne Meijers Heijboer

2017-02-01

Full Text Available Abstract Hereditary cancer refers to cancers caused by germline mutations in cancer predisposing genes. These mutations confer a significantly increased risk of cancer, are rare, and are in the majority of cases autosomal dominantly inherited.  Since the eighties of last century more than 115 cancer predisposing genes have been identified. In many Western countries genetic testing of patients and families with clustering of cancers started early, and was often performed by clinical geneticists (MDs performed the counselling and pedigree analyses and by molecular biologists (in laboratories within departments of clinical genetics.  It turned out to be a long path to fully realize the promise of cancer predisposing genes. The clinical utility of many cancer genetic tests and subsequent risk reducing interventions has not yet been validated and pitfalls in e.g. misinterpretation of genetic variants showed up. However, without doubt genetic testing for mutations will eventually turn out as a strong tool to save lives from early cancer death and will become part of standard cancer care throughout the developed world.  Apart from primary surgical prevention, major progress is to be expected in earlier diagnoses, tailored therapies, and possibly chemoprevention.  Ideally researchers, clinical geneticists, molecular biologists, surgeons, oncologists, gynaecologists and other professionals will work together to reach this goal. Keywords : clinical genetics, germline, hereditary cancers, cancer predisposing genes

Hereditary Kidney Cancer Syndromes and Surgical Management of the Small Renal Mass.

Science.gov (United States)

Nguyen, Kevin A; Syed, Jamil S; Shuch, Brian

2017-05-01

The management of patients with hereditary kidney cancers presents unique challenges to clinicians. In addition to an earlier age of onset compared with patients with sporadic kidney cancer, those with hereditary kidney cancer syndromes often present with bilateral and/or multifocal renal tumors and are at risk for multiple de novo lesions. This population of patients may also present with extrarenal manifestations, which adds an additional layer of complexity. Physicians who manage these patients should be familiar with the underlying clinical characteristics of each hereditary kidney cancer syndrome and the suggested surgical approaches and recommendations of genetic testing for at-risk individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetically caused congenital anomalies of reproductive system

Directory of Open Access Journals (Sweden)

L. F. Kurilo

2013-01-01

Full Text Available Classification of congenital disorders, their frequency of occurrence in populations, and some terminology questions discussed in the review. Genetically caused congenital anomalies of reproductive system are outlined. Full information about genetic syndromes is stated in the book: Kozlova S.I., Demikova N.S. Hereditary syndromes and genetic counseling. M., 2007.

MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers : A study of hereditary nonpolyposis colorectal cancer families

NARCIS (Netherlands)

Vasen, HFA; Stormorken, A; Menko, FH; Nagengast, FM; Kleibeuker, JH; Griffioen, G; Taal, BG; Moller, P; Wijnen, JT

2001-01-01

Purpose: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and

MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families.

NARCIS (Netherlands)

Vasen, H.F.; Stormorken, A.; Menko, F.H.; Nagengast, F.M.; Kleibeuker, J.H.; Griffioen, G.; Taal, B.G.; Moller, P.; Wijnen, J.T.

2001-01-01

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and

Prophylactic total gastrectomy in hereditary diffuse gastric cancer

DEFF Research Database (Denmark)

Bardram, Linda; Hansen, Thomas V O; Gerdes, Anne-Marie

2014-01-01

Inactivating mutations in the CDH1 (E-cadherin) gene are the predisposing cause of gastric cancer in most families with hereditary diffuse gastric cancer (HDGC). The lifetime risk of cancer in mutation positive members is more than 80 % and prophylactic total gastrectomy is recommended. Not all...... mutations in the CDH1 gene are however pathogenic and it is important to classify mutations before this major operation is performed. Probands from two Danish families with gastric cancer and a history suggesting HDGC were screened for CDH1 gene mutations. Two novel CDH1 gene mutations were identified....... Hospital stay was 6-8 days and there were no complications. Small foci of diffuse gastric cancer were found in all patients-intramucosal in six and advanced in one. Preoperative endoscopic biopsies had revealed a microscopic cancer focus in two of the patients. Our data confirmed the pathogenic nature...

[Experience in molecular diagnostic in hereditary neuropathies in a pediatric tertiary hospital].

Science.gov (United States)

Fernández-Ramos, Joaquín A; López-Laso, Eduardo; Camino-León, Rafael; Gascón-Jiménez, Francisco J; Jiménez-González, M Dolores

2015-12-01

Charcot-Marie-Tooth (CMT) is the most common hereditary sensory motor neuropathy. Advances in molecular diagnosis have increased the diagnostic possibilities of these patients. Retrospective study of 36 pediatric patients diagnosed with CMT in a tertiary center in 2003-2015. We found 16 patients were diagnosed by a duplication in PMP22; two cases were diagnosed of hereditary neuropathy with liability to pressure palsies, one with a point mutation in PMP22; a male with a mild demyelinating phenotype, without family history, was diagnosed with GJB1 mutation; in a patient with a peripheral hypotonia at birth and axonal pattern in EMG by mutation in MFN2; a gypsy patient, with consanguineous family, CMT4D, was identified by a mutation in the gene NDRG1; a patient with multiplex congenital arthrogryposis and vocal cord paralysis, whose mother had a scapular-peroneal syndrome, had a congenital spinal muscular atrophy with mild distal axonal neuropathy by mutation in gene TRPV4; three girls, from a gypsy consanguineous family, with axonal CMT with neuromyotonic discharges were diagnosed by a mutation in the gene HINT1; twelve patients haven't molecular diagnosis currently. CMT1A predominated in our series (44%), as previous studies. We emphasize the description of a patient with a mutation in TRPV4 recently described as a cause of CMT2C and three cases, of gypsy consanguineous family, with the same mutation in HINT1 gene, recently described as a cause of axonal neuropathy with neuromyotonia, autosomal recessive (AR-CMT2). The proportion of patients without molecular diagnosis is similar to main European series.

Before and after, the impact of available on-demand treatment for HAE

DEFF Research Database (Denmark)

Christiansen, Sandra C; Bygum, Anette; Banerji, Aleena

2015-01-01

of suffocation, worry about their children inheriting HAE, and medication side effects. Data were analyzed using Wilcoxon signed-rank tests or analysis of variance. Responses were obtained from 134 self-identified HAE subjects: 85 type I, 21 type II, and 28 with normal C1 inhibitor (C1INH). Burden of disease......Availability of effective treatment for acute attacks is expected to transform the care of hereditary angioedema (HAE) patients. We felt that it would be of interest to test these assumptions by examining the perceptions of HAE patients regarding the impact that these therapies have had...

Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort.

LENUS (Irish Health Repository)

Davidson, G L

2012-08-01

The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1\\/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1\\/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN.

Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort.

Science.gov (United States)

Davidson, G L; Murphy, S M; Polke, J M; Laura, M; Salih, M A M; Muntoni, F; Blake, J; Brandner, S; Davies, N; Horvath, R; Price, S; Donaghy, M; Roberts, M; Foulds, N; Ramdharry, G; Soler, D; Lunn, M P; Manji, H; Davis, M B; Houlden, H; Reilly, M M

2012-08-01

The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN.

Renal AA amyloidosis in a patient with hereditary complete complement C4 deficiency

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Imed Helal

2011-01-01

Full Text Available Hereditary complete C4 deficiency has until now been reported in 30 cases only. A disturbed clearance of immune- complexes probably predisposes these individuals to systemic lupus erythematosus, other immune- complex diseases and recurrent microbial infections. We present here a 20- year- old female with hereditary complete C4 deficiency. Renal biopsy demonstrated renal AA amyloidosis. This unique case further substantiates that deficiency of classical pathway components predisposes to the development of recurrent microbial infections and that the patients may develop AA amyloidosis. Furthermore, in clinical practice, the nephrotic syndrome occurring in a patient with hereditary complete complement C4 deficiency should lead to the suspicion of renal AA amyloidosis.

The molecular basis of hereditary enamel defects in humans.

Science.gov (United States)

Wright, J T; Carrion, I A; Morris, C

2015-01-01

The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel. © International & American Associations for

The Molecular Basis of Hereditary Enamel Defects in Humans

Science.gov (United States)

Carrion, I.A.; Morris, C.

2015-01-01

The formation of human enamel is highly regulated at the molecular level and involves thousands of genes. Requisites for development of this highly mineralized tissue include cell differentiation; production of a unique extracellular matrix; processing of the extracellular matrix; altering of cell function during different stages of enamel formation; cell movement and attachment; regulation of ion and protein movement; and regulation of hydration, pH, and other conditions of the microenvironment, to name just a few. Not surprising, there is a plethora of hereditary conditions with an enamel phenotype. The objective of this review was to identify the hereditary conditions listed on Online Mendelian Inheritance in Man (OMIM) that have an associated enamel phenotype and whether a causative gene has been identified. The OMIM database was searched with the terms amelogenesis, enamel, dental, and tooth, and all results were screened by 2 individuals to determine if an enamel phenotype was identified. Gene and gene product function was reviewed on OMIM and from publications identified in PubMed. The search strategy revealed 91 conditions listed in OMIM as having an enamel phenotype, and of those, 71 have a known molecular etiology or linked genetic loci. The purported protein function of those conditions with a known genetic basis included enzymes, regulatory proteins, extracellular matrix proteins, transcription factors, and transmembrane proteins. The most common enamel phenotype was a deficient amount of enamel, or enamel hypoplasia, with hypomineralization defects being reported less frequently. Knowing these molecular defects allows an initial cataloging of molecular pathways that lead to hereditary enamel defects in humans. This knowledge provides insight into the diverse molecular pathways involved in enamel formation and can be useful when searching for the genetic etiology of hereditary conditions that involve enamel. PMID:25389004

SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis.

Science.gov (United States)

Orlacchio, Antonio; Babalini, Carla; Borreca, Antonella; Patrono, Clarice; Massa, Roberto; Basaran, Sarenur; Munhoz, Renato P; Rogaeva, Ekaterina A; St George-Hyslop, Peter H; Bernardi, Giorgio; Kawarai, Toshitaka

2010-02-01

The mutation of the spatacsin gene is the single most common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene. The inclusion criterion was a diagnosis of clinically definite amyotrophic lateral sclerosis according to the revised El Escorial criteria. The exclusion criterion was a diagnosis of hereditary spastic paraplegia with thin corpus callosum in line with an established protocol. Additional pathological and genetic evaluations were also performed. Surprisingly, 12 sequence alterations in the spatacsin gene (one of which is novel, IVS30 + 1 G > A) were identified in 10 unrelated pedigrees with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival. The countries of origin of these families were Italy, Brazil, Canada, Japan and Turkey. The variants seemed to be pathogenic since they co-segregated with the disease in all pedigrees, were absent in controls and were associated with amyotrophic lateral sclerosis neuropathology in one member of one of these families for whom central nervous system tissue was available. Our study indicates that mutations in the spatascin gene could cause a much wider spectrum of clinical features than previously recognized, including autosomal recessive juvenile amyotrophic lateral sclerosis.

Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study

DEFF Research Database (Denmark)

Park, Jae-Gahb; Kim, Duck-Woo; Hong, Chang Won

2006-01-01

PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members of the Internatio......PURPOSE: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC). EXPERIMENTAL DESIGN: A questionnaire was mailed to 55 members...... of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations. RESULTS: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs. SBC was the first...... HNPCC-associated malignancy in 14 of 41 (34.1%) patients for whom a personal history of HNPCC-associated cancers was available. The study population harbored 69 different germ line mismatch repair gene mutations, including 31 mutations in MLH1, 34 in MSH2, 3 in MSH6, and 1 in PMS2. We compared...

The technical hereditary of CWD

International Nuclear Information System (INIS)

Smulders, P.T.

1990-01-01

An overview is given of the activities of the Dutch foundation CWD since 1975. The financing of the foundation stopped July 1st 1990. From 1975 the CWD stimulated the use of small scale wind energy to pump up water in developing countries. The hereditary of the CWD consists of knowledge of the design and performance of components of wind mills, knowledge to design integral systems based on these components and preconditions, and knowledge how to manufacture, install and maintain the wind mills locally. The CWD designed three wind mill pumps of which 250 have been brought into operation in developing countries. A CWD-type pump was developed in Sri-Lanka of which 150 pumps were installed. Also attention is paid to the external situation which effected the CWD activities: the lack of interest from the Dutch industry to cooperate in developing CWD pumps; the actual market far away in developing countries; and too little competition in the research and development. The nature of the CWD-participants caused some internal friction which did not contribute to the effectivity of the CWD organisation. It is recommended to continue the development and testing of small wind energy systems and to preserve the knowledge gained by the CWD. 3 figs., 2 tabs., 3 refs

Psychological distress in women at risk for hereditary breast cancer: the role of family communication and perceived social support.

Science.gov (United States)

den Heijer, Mariska; Seynaeve, Caroline; Vanheusden, Kathleen; Duivenvoorden, Hugo J; Bartels, Carina C M; Menke-Pluymers, Marian B E; Tibben, Aad

2011-12-01

Hereditary breast cancer has a profound impact on individual family members and on their mutual communication and interactions. The way at-risk women cope with the threat of hereditary breast cancer may depend on the quality of family communication about hereditary breast cancer and on the perceived social support from family and friends. To examine the associations of family communication and social support with long-term psychological distress in a group of women at risk for hereditary breast cancer, who opted either for regular breast surveillance or prophylactic surgery. The study cohort consisted of 222 women at risk for hereditary breast cancer, who previously participated in a study on the psychological consequences of either regular breast cancer surveillance or prophylactic surgery. General and breast cancer specific distress, hereditary cancer-related family communication, perceived social support, and demographics were assessed. Using structural equation modelling, we found that open communication about hereditary cancer within the family was associated with less general and breast cancer specific distress. In addition, perceived support from family and friends was indirectly associated with less general and breast cancer-specific distress through open communication within the family. These findings indicate that family communication and perceived social support from friends and family are of paramount importance in the long-term adaptation to being at risk for hereditary breast cancer. Attention for these issues needs to be incorporated in the care of women at risk for hereditary breast cancer. Copyright © 2010 John Wiley & Sons, Ltd.

X-ray criteria of the differential diagnosis of hereditary tubulopathies in children

International Nuclear Information System (INIS)

Bosin, V.Yu.; Kondrina, V.V.; Mulyk, T.E.; Verbitskaya, A.I.

1995-01-01

In search for x-ray signs of skeletal involvement specific for each type of hereditary tubulopathies Vitamin D-resistant rickets, Renal tubular acidosis, Toni-Debre-Fanconi disease, the authors analyze the results of clinical and X-ray examinations of 144 children aged 2 to 16. Study demonstrated the possibility and high reliability of X-ray differential diagnosis of various forms of hereditary tubulopathies in children. 5 refs., 8 figs., 2 tabs

Spinal Exostosis in a Boy with Multiple Hereditary Exostoses

Directory of Open Access Journals (Sweden)

Ali Al Kaissi

2013-01-01

Full Text Available We report on a 13-year-old boy who presented with multiple hereditary exostosis and had development of back pain, associated with neurological deficits, and was found to have exostoses in the spinal canal. Spine radiograph showed a cauliflower-like abnormality of multiple exostoses of the posterior arch (pedicle of the thoracic vertebrae (T3–5. Reformatted CT scanning revealed the simultaneous development of intra- and extraspinal osteochondromatosis of T3–5. The spinal cord was compressed by the intraspinal exostosis. Our patient was surgically treated for intraspinal exostoses and showed cessation of neurological deficits. We report what might be a rare association of spinal cord compression in a patient with multiple hereditary exostoses.

Ventricular assist device implantation in a young patient with non-compaction cardiomyopathy and hereditary spherocytosis.

Science.gov (United States)

Huenges, Katharina; Panholzer, Bernd; Cremer, Jochen; Haneya, Assad

2018-04-01

A case of a 15-year-old female patient with acute heart failure due to non-compaction cardiomyopathy and hereditary anaemia (hereditary spherocytic elliptocytosis) requiring ventricular assist device implantation as a bridge to transplantation is presented. The possible effects of mechanical stress on erythrocytes potentially induced by mechanical circulatory support remains unclear, but it may lead to haemolytic crisis in patients suffering from hereditary anaemia. In our case, ventricular assist device therapy was feasible, and haematological complications did not occur within 6 weeks of bridging our patient to heart transplantation.

Fruit-induced FPIES masquerading as hereditary fructose intolerance.

Science.gov (United States)

Fiocchi, Alessandro; Dionisi-Vici, Carlo; Cotugno, Giovanna; Koch, Pierluigi; Dahdah, Lamia

2014-08-01

Hereditary fructose intolerance (HFI) symptoms develop at first introduction of fruit during weaning. We report on an infant with suspected HFI who presented with repeated episodes of vomiting and hypotension after ingestion of fruit-containing meals. The first episode occurred at age 4 months. Despite negative genetic testing for HFI, strict avoidance of fruit ingestion resulted in lack of recurrence of symptoms. Oral-fructose-tolerance testing conducted with an apple mousse did not determine hypoglycemia or fructosuria but caused severe hypotension. Allergy evaluations were negative, and the history was diagnostic for fruit-induced food protein-induced enterocolitis syndrome. Because this non-immunoglobulin E-mediated gastrointestinal food hypersensitivity manifests as profuse, repetitive vomiting, often with diarrhea, leading to acute dehydration and lethargy, it may be misinterpreted as HFI. We advise pediatricians to consider food protein-induced enterocolitis syndrome in the differential diagnosis when there is a suspicion of HFI. Copyright © 2014 by the American Academy of Pediatrics.

Sepsis and siderosis, Yersinia enterocolitica and hereditary haemochromatosis.

Science.gov (United States)

Thwaites, Phoebe A; Woods, Marion L

2017-01-04

A 60-year-old woman was admitted with sepsis, relative bradycardia, CT evidence of numerous small liver abscesses and 'skin bronzing' consistent with hereditary haemochromatosis (HH). Yersinia enterocolitica O:9 infection was confirmed by serology specimens taken 10 days apart. Iron overload was detected, and homozygous C282Y gene mutation confirmed HH. Liver biopsy revealed grade IV siderosis with micronodular cirrhosis. Haemochromatosis is a common, inherited disorder leading to iron overload that can produce end-organ damage from excess iron deposition. Haemochromatosis diagnosis allowed aggressive medical management with phlebotomy achieving normalisation of iron stores. Screening for complications of cirrhosis was started that included hepatoma surveillance. Iron overload states are known to increase patient susceptibility to infections caused by lower virulence bacteria lacking sophisticated iron metabolism pathways, for example, Yersinia enterocolitica Although these serious disseminated infections are rare, they may serve as markers for occult iron overload and should prompt haemochromatosis screening. 2017 BMJ Publishing Group Ltd.

Allelic Dropout in the ENG Gene, Affecting the Results of Genetic Testing in Hereditary Hemorrhagic Telangiectasia

DEFF Research Database (Denmark)

Tørring, Pernille M; Kjeldsen, A.D.; Ousager, L.B.

2012-01-01

Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder with three disease-causing genes identified to date: ENG, ACVRL1, and SMAD4. We report an HHT patient with allelic dropout that on routine sequence analysis for a known mutation in the family (c.817......-3T>G in ENG) initially seemed to be homozygous for the mutation. Aim: To explore the possibility of allelic dropout causing a false result in this patient. Methods: Mutation analysis of additional family members was performed and haplotype analysis carried out. New primers were designed to reveal...... the presence of a possible sequence variant, which could explain the presumed allelic dropout. Results: Allelic dropout caused by a six-nucleotide duplication close to the standard reverse primer was the assumed cause of a false homozygous diagnosis. Conclusion: Sequence variants outside of the primer regions...

Molecular biology of hereditary diabetes insipidus.

Science.gov (United States)

Fujiwara, T Mary; Bichet, Daniel G

2005-10-01

The identification, characterization, and mutational analysis of three different genes-the arginine vasopressin gene (AVP), the arginine vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2 [AQP2])-provide the basis for understanding of three different hereditary forms of "pure" diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked nephrogenic diabetes insipidus (NDI), and non-X-linked NDI, respectively. It is clinically useful to distinguish two types of hereditary NDI: A "pure" type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients who have congenital NDI and bear mutations in the AVPR2 or AQP2 genes have a "pure" NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride, and calcium. Patients who bear inactivating mutations in genes (SLC12A1, KCNJ1, CLCNKB, CLCNKA and CLCNKB in combination, or BSND) that encode the membrane proteins of the thick ascending limb of the loop of Henle have a complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium. These advances provide diagnostic and clinical tools for physicians who care for these patients.

Unstable mutations: cause of some neurological hereditary diseases

International Nuclear Information System (INIS)

Cuenca Berger, P.; Morales Montero, F.

1999-01-01

Unstable mutations or amplification of triplets constitute a kind of genetic alteration discovered during the last decade. They had been found inside or near genes important for the normal neurological function of the human being. In some cases, the presence of the amplification causes the inactivation of the gene or the synthesis of a new product which functions different from the original protein. Some common characteristics of diseases caused by the amplification of triplets are that it affects the nervous system and are degenerative in nature. The expression of the manifestations varies according to age. Most of them show genetic anticipation in which the severity of the manifestations increases with each generation and appear at an earlier age. In most cases, the severity of the symptoms is correlated positively to the size of the amplification. The diagnosis of an affected individual in a family may indicate the presence of an altered gene in other relatives. These relatives may not present evident signs of the illness either because it is of late onset or because they carry premutations. The molecular diagnosis of these mutations is important to estimate the risk of developing the disease and/or of transmitting the illness to the descendants and to eliminate the fears of healthy relatives who have inherited normal copies of the gene. (Author) [es

Genetic deficiency of the α subunit of the guanine nucleotide-binding protein G/sub s/ as the molecular basis for Albright hereditary osteodystrophy

International Nuclear Information System (INIS)

Levine, M.A.; Ahn, T.G.; Klupt, S.F.; Kaufman, K.D.; Smallwood, P.M.; Bourne, H.R.; Sullivan, K.A.; Van Dop, C.

1988-01-01

Patients who have pseudohypoparathyroidism type I associated with Albright hereditary osteodystrophy commonly have a genetic deficiency of the α subunit of the G protein that stimulated adenylyl cyclase αG/sub s/. To discover the molecular mechanism that causes αG/sub s/ deficiency in these patients, the authors examined eight kindreds with one or more members affected with Albright hereditary osteodystrophy or pseudohypoparathyroidism and αG/sub s/ deficiency. In these families, αG/sub s/, deficiency and the Albright hereditary osteodystrophy phenotype were transmitted together in a dominant inheritance pattern. Using a cDNA hybridization probe for αG/sub s/, restriction analysis with several analysis with several endonucleases showed no abnormalities of restriction fragments or gene dosage. RNA blot and dot blot analysis of total RNA from cultured fibroblasts obtained from the patients revealed ∼ 50% reduced mRNA levels for αG/sub s/ in affected members of six of the pedigrees but normal levels in affected members of the two other pedigrees, compared to mRNA levels in fibroblasts from unaffected individuals. By contrast, mRNA levels encoding the α subunit of the G protein that inhibits adenylyl cyclase were not altered. These findings suggest that several molecular mechanisms produce αG/sub s/ deficiency in patients with pseudohypoparathyroidism type Ia and that major gene rearrangements or deletions are not a common cause for αG/sub s/ deficiency in pseudohypoparathyroidism type I

Clinicoelectrophysiologic and magnetoresonance and tomographic investigation of hereditary and congenital diseases of the brain

International Nuclear Information System (INIS)

Kamalov, I.I.; Pikuza, O.I.; Idrisova, L.G.; Uryvskij, V.I.

1996-01-01

The combined investigation of hereditary and congenital diseases of the brain using magnetoresonance tomography is performed. The hereditary and congenital diseases of the brain accompanied by disorders of liquoroconductive tracts with medullary substance lesion are revealed. The investigation results provide timely development of the treatment tactics and rehabilitation of sick children. Refs. 3

Repair and replication of DNA in hereditary (bilateral) retinoblastoma cells after X-irradiation

International Nuclear Information System (INIS)

Cleaver, J.E.; Char, D.; Charles, W.C.; Rand, N.

1982-01-01

Fibroblasts from patients with hereditary retinoblastoma reportedly exhibit increased sensitivity to killing by X-rays. Although some human syndromes with similar or greater hypersensitivity to DNA-damaging agents (e.g., X-rays, ultraviolet light, and chemical carcinogens), such as xeroderma pigmentosum, are deficient in DNA repair, most do not have such clearly demonstrable defects in repair. Retinoblastoma cells appear to be normal in repairing single-strand breaks and performing repair replication after X-irradiation and also in synthesizing poly(adenosine diphosphoribose). Semiconservative DNA replication in these cells, however, is slightly more resistant than normal after X-irradiation, suggesting that continued replication of damaged parental DNA could contribute to the pathogenesis of the disease. This effect is small, however, and may be a consequence rather than a cause of the fundamental enzymatic abnormality in retinoblastoma that causes the tumorigenesis

Modeling neurodevelopment and cortical dysfunction in SPG11-linked hereditary spastic paraplegia using human induced pluripotent stem cells

OpenAIRE

Mishra, Himanshu Kumar

2016-01-01

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of inherited motor neuron diseases characterized by progressive spasticity and weakness of the lower limbs. Mutations in the Spastic Paraplegia Gene11 (SPG11), encoding spatacsin, cause the most frequent form of autosomal recessive HSP. SPG11 patients are clinically distinguishable from most other HSPs, by severe cortical atrophy and presence of a thin corpus callosum (TCC), associated with cognitive deficits. Partly due to l...

Hereditary Causes of Kidney Stones and Chronic Kidney Disease

Science.gov (United States)

Edvardsson, Vidar O.; Goldfarb, David S.; Lieske, John C.; Beara-Lasic, Lada; Anglani, Franca; Milliner, Dawn S.; Palsson, Runolfur

2013-01-01

Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. A high index of suspicion coupled with early diagnosis may reduce or even prevent the serious long-term complications of these diseases. In this paper, we review the epidemiology, clinical features, diagnosis, treatment and outcome of patients with APRT deficiency, cystinuria, Dent disease, FHHNC and PH with emphasis on childhood manifestations. PMID:23334384

A De Novo Mutation in Causes Generalized Dystonia in 2 Unrelated Children

Directory of Open Access Journals (Sweden)

Yasemin Gulcan Kurt MD

2016-03-01

Full Text Available Dystonia is often associated with the symmetrical basal ganglia lesions of Leigh syndrome. However, it has also been associated with mitochondrial ND mutations, with or without Leber hereditary optic neuropathy. The m.14459G>A mutation in ND6 causes dystonia with or without familial Leber hereditary optic neuropathy. We report heteroplasmic 14459G>A mutations in 2 unrelated children with nonmaternally inherited generalized dystonia and showing bilateral magnetic resonance imaging lesions in nucleus pallidus and putamen. Both children have reached their teenage years, and they are intellectually active, despite their motor problems.

Next generation sequencing for molecular confirmation of hereditary sudden cardiac death syndromes.

Science.gov (United States)

Márquez, Manlio F; Cruz-Robles, David; Ines-Real, Selene; Vargas-Alarcón, Gilberto; Cárdenas, Manuel

2015-01-01

Hereditary sudden cardiac death syndromes comprise a wide range of diseases resulting from alteration in cardiac ion channels. Genes involved in these syndromes represent diverse mutations that cause the altered encoding of the diverse proteins constituting these channels, thus affecting directly the currents of the corresponding ions. In the present article we will briefly review how to arrive to a clinical diagnosis and we will present the results of molecular genetic studies made in Mexican subjects attending the SCD Syndromes Clinic of the National Institute of Cardiology of Mexico City. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia

DEFF Research Database (Denmark)

Kjeldsen, A D; Kjeldsen, J

2000-01-01

Gastrointestinal bleeding occurs in a number of patients with hereditary hemorrhagic telangiectasia (HHT) and may lead to a high transfusion need. The aim of this study was to estimate the occurrence and severity of gastrointestinal bleeding in a geographically well defined HHT population....

Sulindac treatment in hereditary non-pollyposis colorectal cancer

NARCIS (Netherlands)

Rijcken, Fleur E. M.; Hollema, Harry; van der Zee, Ate G. J.; van der Sluis, Tineke; Ek, Wytske Boersma-van; Kleibeuker, Jan H.

Non-steroidal anti-inflammatory drugs, e.g. sulindac have been extensively studied for chemoprevention in familial adenomatous polyposis, but not in hereditary non-polyposis colorectal cancer (HNPCC). We evaluated these effects in HNPCC using surrogate end-points for cancer risk. In a randomised

Familial cosegregation of manic-depressive illness and a form of hereditary cerebellar ataxia

Energy Technology Data Exchange (ETDEWEB)

Piqueras, J.F.; Santos, J.; Puertollano, R. [Universidad Autonoma, Madrid (Spain)] [and others

1995-06-19

We report on a Spanish family with co-occurrence of manic-depression and a form of hereditary cerebellar ataxia. All affected individuals in the second generation showed cerebellar ataxia and manic-depression simultaneously. Since anticipation has been described in both disorders and the pattern of segregation may be autosomal as well as X-linked, we have searched for a possible involvement of two candidate genes which are located either on an autosome (SCA1) or on the X-chromosome (GABRA3). We concluded that expansion of trinucleotide repeats at SCA1 gene cannot be considered as a disease-causing mutation, and this gene should be initially discarded. 19 refs., 3 figs.

Hereditary Colorectal Cancer (CRC Program in Latvia

Directory of Open Access Journals (Sweden)

Irmejs Arvids

2003-12-01

Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

The N355K atlastin 1 mutation is associated with hereditary sensory neuropathy and pyramidal tract features.

Science.gov (United States)

Leonardis, L; Auer-Grumbach, M; Papić, L; Zidar, J

2012-07-01

  Mutations in atlastin-1 (ATL-1), a gene known to cause pure, early-onset autosomal dominant hereditary spastic paraplegia SPG3A, have been recently reported to cause hereditary sensory neuropathy I (HSN I). We describe the detailed clinical and electrophysiologic findings in the first family with ulcero-mutilating sensory neuropathy carrying the c. C1065A, p.N355K mutation in ATL-1.   Detailed clinical and electrophysiologic studies were performed in affected and at-risk family members. Motor and sensory nerve conductions studies (NCS) were carried out in upper and lower limbs. ATL-1 was screened for mutations by direct sequencing.   Ten patients were found to carry the N355K mutation. With the exception of the two youngest patients, all had trophic skin changes in the feet consisting mainly of painless ulcers. Frequently, amputation of toes, feet, or even more proximal parts of the lower legs became necessary. A variable degree of increased muscle tone was observed in younger patients, whilst some older affected individuals only presented with hyperreflexia of patellar tendon reflexes. NCS revealed signs of an axonal motor and sensory neuropathies.   Our family carrying the N355K ATL1 mutation, which was initially diagnosed as HSN I, enlarges the SPG3A phenotype. We therefore suggest that patients with HSN I excluded for more common causes of HSN I, and in particular, affected individuals who exhibit additional pyramidal tract features should also be screened for mutations in ATL1. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Cellular Pathways of Hereditary Spastic Paraplegia*

OpenAIRE

Blackstone, Craig

2012-01-01

Human voluntary movement is controlled by the pyramidal motor system, a long CNS pathway comprising corticospinal and lower motor neurons. Hereditary spastic paraplegias (HSPs) are a large, genetically diverse group of inherited neurologic disorders characterized by a length-dependent distal axonopathy of the corticospinal tracts, resulting in lower limb spasticity and weakness. A range of studies are converging on alterations in the shaping of organelles, particularly the endoplasmic reticul...

Hereditary iron and copper deposition

DEFF Research Database (Denmark)

Aaseth, Jan; Flaten, Trond Peder; Andersen, Ole

2007-01-01

Hereditary deposition of iron (primary haemochromatosis) or copper (Wilson's disease) are autosomal recessive metabolic disease characterized by progressive liver pathology and subsequent involvement of various other organs. The prevalence of primary haemochromatosis is approximately 0.5%, about......, they may be inadequate in patients diagnosed so late that extensive body deposits of metal have been developed. The main research needs in this field are to further clarify molecular mechanisms of disease progression and to develop new chelators that are more effective and less toxic than those presently...

Hereditary hemochromatosis: genetic complexity and new diagnostic approaches.

NARCIS (Netherlands)

Swinkels, D.W.; Janssen, M.C.H.; Bergmans, J.; Marx, J.J.M.

2006-01-01

Since the discovery of the hemochromatosis gene (HFE) in 1996, several novel gene defects have been detected, explaining the mechanism and diversity of iron-overload diseases. At least 4 main types of hereditary hemochromatosis (HH) have been identified. Surprisingly, genes involved in HH encode for

Red cell 2,3-diphosphoglycerate levels in children with hereditary haemolytic anaemias.

Science.gov (United States)

Haidas, S; Zannos-Mariolea, L; Matsaniotis, N

1975-12-01

The role of red cell 2,3-diphosphoglycerate (2,3-DPG) in increasing the availability of haemoglobin oxygen in neonatal jaundice and hereditary haemolytic anaemias was investigated. Measurements of 2,3-DPG were carried out on 58 normal children and six normal adults, 18 full-term newborns with neonatal jaundice and 57 cases (51 children and six adults) with hereditary haemolytic anaemias. In normal children and adults, with a mean haemoglobin of 12.69 g/dl, mean 2,3-DPG was 14.90 mumol/g Hb. In jaundiced newborns with a mean haemoglobin of 16.04 g/dl mean 2,3-DPG levels were 14.51 mumol/g Hb, i.e. normal. 2,3-DPG levels were increased in patients with beta-thalassaemia major, alpha-thalassaemia, sickle-cell disease, favism, hereditary spherocytosis and in heterozygotes for beta-thalassaemia with increased haemoglobin F. In heterozygotes for beta-thalassaemia with increased haemoglobin A2 only and in sickle cell trait 2,3-DPG levels were normal.

Comparison of Attitudes Regarding Preimplantation Genetic Diagnosis Among Patients with Hereditary Cancer Syndromes

Science.gov (United States)

Rich, Thereasa A.; Liu, Mei; Etzel, Carol J.; Bannon, Sarah A.; Mork, Maureen E.; Ready, Kaylene; Saraiya, Devki S.; Grubbs, Elizabeth G.; Perrier, Nancy D.; Lu, Karen H.; Arun, Banu K.; Woodard, Terri L.; Schover, Leslie R.; Litton, Jennifer K.

2014-01-01

Introduction Preimplantation Genetic Diagnosis (PGD) allows couples to avoid having a child with an inherited condition, potentially reducing cancer burden in families with a hereditary cancer predisposition. This study investigated awareness and acceptance of PGD among patients with hereditary cancer syndromes. Methods Questionnaires were mailed to 984 adults with hereditary breast and ovarian cancer, Lynch syndrome, familial adenomatous polyposis, or multiple endocrine neoplasia type 1 or 2. Associations between clinical, demographic, and psychosocial factors and awareness and acceptance of PGD were examined. Results Of 370 respondents (38% return rate), 28% felt their syndrome impacted family planning, 24% were aware of PGD, 72% felt that PGD should be offered, 43% would consider using PGD, and 29% were uncertain. Family experience and syndrome-specific characteristics, such as disease severity, quality of life and availability of medical interventions as well as gender, family planning stage, and religiosity impact perceptions of the acceptability of PGD, though a high level of uncertainty exists. Conclusion Hereditary cancer patients' opinions about the acceptability of PGD are similar to those of genetics and ethical experts. Patients should be told about PGD given that most had not heard of PGD, but feel that PGD should be offered. PMID:24072553

[Mutations of ACVRL1 gene in a pedigree with hereditary hemorrhagic telangiectasia].

Science.gov (United States)

Luo, Jie-wei; Chen, Hui; Yang, Liu-qing; Zhu, Ai-lan; Wu, Yan-an; Li, Jian-wei

2008-06-01

To identify the activin A receptor type II-like 1 gene (ACVRL1) mutations in a Chinese family with hereditary hemorrhagic telangiectasia (HHT2). The exons 3, 7 and 8 of ACVRL1 gene of the proband and her five family members were amplified by polymerase chain reaction (PCR), and the PCR products were sequenced. The proband had obvious telangiectasis of gastric mucosa, and small arteriovenous fistula in the right kidney. All the patients in the HHT2 family had iterative epistaxis or bleeding in other sites, and had telangiectasis of nasal mucosa, tunica mucosa oris and finger tips. ACVRL1 gene analysis confirmed that there is frameshift mutation caused by deletion of G145 in exon 3 in the 4 patients, but the mutation is absent in 2 members without HHT2. The HHT2 family is caused by a 145delG mutation of ACVRL1 gene, resulting in frameshift and a new stop codon at codon 53.

Hereditary neuromuscular diseases

Energy Technology Data Exchange (ETDEWEB)

Oezsarlak, O. E-mail: ozkan.ozsarlak@uza.be; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J

2001-12-01

This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

Genetic and phenotypic characterization of complex hereditary spastic paraplegia

Science.gov (United States)

Kara, Eleanna; Tucci, Arianna; Manzoni, Claudia; Lynch, David S.; Elpidorou, Marilena; Bettencourt, Conceicao; Chelban, Viorica; Manole, Andreea; Hamed, Sherifa A.; Haridy, Nourelhoda A.; Federoff, Monica; Preza, Elisavet; Hughes, Deborah; Pittman, Alan; Jaunmuktane, Zane; Brandner, Sebastian; Xiromerisiou, Georgia; Wiethoff, Sarah; Schottlaender, Lucia; Proukakis, Christos; Morris, Huw; Warner, Tom; Bhatia, Kailash P.; Korlipara, L.V. Prasad; Singleton, Andrew B.; Hardy, John; Wood, Nicholas W.; Lewis, Patrick A.

2016-01-01

Abstract The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15 , SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease-causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining

In vitro sensitivity of normal and hereditary retinoblastoma fibroblasts to DNA-damaging agents

International Nuclear Information System (INIS)

Woods, W.G.; Byrne, T.D.

1986-01-01

We investigated the ability of nine fibroblast cell strains from patients with the hereditary form of retinoblastoma (RB) to handle various types of DNA-damaging agents and compared the results with those obtained in nine normal strains. Cell strains were exposed to gamma-radiation, which causes DNA scission; actinomycin D, a DNA-intercalating agent; and mitomycin C, a bifunctional alkylating agent leading to DNA-DNA cross-linking. Cell strains were studied for their ability to survive in a cytotoxicity assay. Nine normal strains exhibited a mean D0 (inverse of the slope of the straight line portion of the survival curve) of 134-178 cGy after radiation exposure, compared to a range of 119-186 cGy in the nine RB strains (P = 0.33). Similarly, exposure to actinomycin D led to D0 values of 0.024-0.069 microgram/ml in the nine normal strains and D0 values of 0.016-0.067 microgram/ml in the RB strains (P = 0.64). The nine RB strains did exhibit a small overall increase in sensitivity after exposure to mitomycin C, with D0 values ranging from 0.14-0.32 microgram/ml versus 0.19-0.66 microgram/ml in the nine normal strains (P = 0.002); however, when the two most resistant normal strains were excluded from analysis, results were similar. Three RB cell strains derived from individuals who had either developed second cancers or who had a family history of additional sarcomas consistently exhibited increases in sensitivity to all three DNA-damaging agents studied compared with other hereditary RB cell strains as well as normal strains. The results suggest that normal human fibroblast cell strains exhibit a wide response to DNA-damaging agents, especially chemical agents. Most hereditary RB strains exhibit sensitivity well within the normal range; however, strains from RB patients predisposed to second cancers exhibit increases in sensitivity to DNA-damaging agents

Hereditary effects in eccentric compact binary inspirals to third post-Newtonian order

Science.gov (United States)

Loutrel, Nicholas; Yunes, Nicolás

2017-02-01

While there has been much success in understanding the orbital dynamics and gravitational wave emission of eccentric compact binaries in the post-Newtonian formalism, some problems still remain. The largest of these concerns hereditary effects: non-linear phenomena related to the scattering off of the background curved spacetime (tails) and to the generation of gravitational waves by gravitational waves (memory). Currently, these hereditary effects are only known numerically for arbitrary eccentricity through infinite sums of Bessel functions, with closed-form, analytic results only available in the small eccentricity limit. We here calculate, for the first time, closed-form, analytic expressions for all hereditary effects to third post-Newtonian order in binaries with arbitrary eccentricity. For the tails, we first asymptotically expand all Bessel functions in high eccentricity and find a superasymptotic series for each enhancement factor, accurate to better than 10-3 relative to post-Newtonian numerical calculations at all eccentricities. We further improve the small-eccentricity behavior of the superasymptotic series by generating hyperasymptotic expressions for each enhancement factor, typically accurate to better than 10-8 at all eccentricities. For the memory, we discuss its computation within the context of an osculating approximation of the binary’s orbit and the difficulties that arise. Our closed-form analytic expressions for the hereditary fluxes allow us to numerically compute orbital phases that are identical to those found using an infinite sum of Bessel functions to double numerical precision.

Hereditary effects in eccentric compact binary inspirals to third post-Newtonian order

International Nuclear Information System (INIS)

Loutrel, Nicholas; Yunes, Nicolás

2017-01-01

While there has been much success in understanding the orbital dynamics and gravitational wave emission of eccentric compact binaries in the post-Newtonian formalism, some problems still remain. The largest of these concerns hereditary effects: non-linear phenomena related to the scattering off of the background curved spacetime (tails) and to the generation of gravitational waves by gravitational waves (memory). Currently, these hereditary effects are only known numerically for arbitrary eccentricity through infinite sums of Bessel functions, with closed-form, analytic results only available in the small eccentricity limit. We here calculate, for the first time, closed-form, analytic expressions for all hereditary effects to third post-Newtonian order in binaries with arbitrary eccentricity. For the tails, we first asymptotically expand all Bessel functions in high eccentricity and find a superasymptotic series for each enhancement factor, accurate to better than 10 −3 relative to post-Newtonian numerical calculations at all eccentricities. We further improve the small-eccentricity behavior of the superasymptotic series by generating hyperasymptotic expressions for each enhancement factor, typically accurate to better than 10 −8 at all eccentricities. For the memory, we discuss its computation within the context of an osculating approximation of the binary’s orbit and the difficulties that arise. Our closed-form analytic expressions for the hereditary fluxes allow us to numerically compute orbital phases that are identical to those found using an infinite sum of Bessel functions to double numerical precision. (paper)

Severe angioedema in myxedema coma: a difficult airway in a rare endocrine emergency.

Science.gov (United States)

Lee, Christopher H; Wira, Charles R

2009-10-01

Myxedema coma is the most lethal manifestation of hypothyroidism. It is a true medical emergency and can result in profound hemodynamic instability and airway compromise. Myxedema coma currently remains a diagnostic challenge due to the rarity of cases seen today, and failure to promptly initiate therapy with replacement thyroid hormone can be fatal. As thyroid hormone therapy can take days or weeks to reverse the manifestations of myxedema coma, interim supportive therapy is critical while awaiting clinical improvement. Some patients will require endotracheal intubation in the emergency department (ED), and physicians should be aware that unanticipated posterior pharyngeal edema in myxedema coma could severely complicate airway management. Although mechanical ventilation is a well-described adjunctive therapy for myxedema coma, reports of the potential difficulty in securing a definitive airway in these patients are rare. We describe a case of an unidentified woman who presented to the ED with myxedema coma requiring urgent endotracheal intubation and was found to have extensive posterior pharyngeal angioedema inconsistent with her relatively benign external examination. This case highlights the typical features of myxedema coma and discusses our necessity for a rescue device in definitive endotracheal tube placement. Emergency physicians should anticipate a potentially difficult airway in all myxedema coma patients regardless of the degree of external facial edema present.

Leber hereditary optic neuropathy: current perspectives

Science.gov (United States)

Meyerson, Cherise; Van Stavern, Greg; McClelland, Collin

2015-01-01

Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. PMID:26170609

The Molecular Basis for Altered Cation Permeability in Hereditary Stomatocytic Human Red Blood Cells

Directory of Open Access Journals (Sweden)

Joanna F. Flatt

2018-04-01

Full Text Available Normal human RBCs have a very low basal permeability (leak to cations, which is continuously corrected by the Na,K-ATPase. The leak is temperature-dependent, and this temperature dependence has been evaluated in the presence of inhibitors to exclude the activity of the Na,K-ATPase and NaK2Cl transporter. The severity of the RBC cation leak is altered in various conditions, most notably the hereditary stomatocytosis group of conditions. Pedigrees within this group have been classified into distinct phenotypes according to various factors, including the severity and temperature-dependence of the cation leak. As recent breakthroughs have provided more information regarding the molecular basis of hereditary stomatocytosis, it has become clear that these phenotypes elegantly segregate with distinct genetic backgrounds. The cryohydrocytosis phenotype, including South-east Asian Ovalocytosis, results from mutations in SLC4A1, and the very rare condition, stomatin-deficient cryohydrocytosis, is caused by mutations in SLC2A1. Mutations in RHAG cause the very leaky condition over-hydrated stomatocytosis, and mutations in ABCB6 result in familial pseudohyperkalemia. All of the above are large multi-spanning membrane proteins and the mutations may either modify the structure of these proteins, resulting in formation of a cation pore, or otherwise disrupt the membrane to allow unregulated cation movement across the membrane. More recently mutations have been found in two RBC cation channels, PIEZO1 and KCNN4, which result in dehydrated stomatocytosis. These mutations alter the activation and deactivation kinetics of these channels, leading to increased opening and allowing greater cation fluxes than in wild type.

Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study

OpenAIRE

Chu Annie TW; Bonanno George A; Ho Judy WC; Ho Samuel MY; Chan Emily MS

2010-01-01

Abstract Background - Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC. Methods - A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer R...

Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12

Science.gov (United States)

Landouré, Guida; Zhu, Peng-Peng; Lourenço, Charles M.; Johnson, Janel O.; Toro, Camilo; Bricceno, Katherine V.; Rinaldi, Carlo; Meilleur, Katherine G.; Sangaré, Modibo; Diallo, Oumarou; Pierson, Tyler M.; Ishiura, Hiroyuki; Tsuji, Shoji; Hein, Nichole; Fink, John K.; Stoll, Marion; Nicholson, Garth; Gonzalez, Michael; Speziani, Fiorella; Dürr, Alexandra; Stevanin, Giovanni; Biesecker, Leslie G.; Accardi, John; Landis, Dennis M. D.; Gahl, William A.; Traynor, Bryan J.; Marques, Wilson; Züchner, Stephan; Blackstone, Craig; Fischbeck, Kenneth H.; Burnett, Barrington G.

2013-01-01

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three-nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly-conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain. PMID:23857908

Autosomal dominant hereditary ataxia in Sri Lanka

OpenAIRE

Sumathipala, Dulika S; Abeysekera, Gayan S; Jayasekara, Rohan W; Tallaksen, Chantal ME; Dissanayake, Vajira HW

2013-01-01

Background Spinocerebellar ataxias (SCA) are a group of hereditary neurodegenerative disorders. Prevalence of SCA subtypes differ worldwide. Autosomal dominant ataxias are the commonest types of inherited ataxias seen in Sri Lanka. The aim of the study is to determine the genetic etiology of patients with autosomal dominant ataxia in Sri Lanka and to describe the clinical features of each genetic subtype. Methods ...

[Molecular genetic diagnostics and screening of hereditary hemochromatosis].

Science.gov (United States)

Zlocha, J; Kovács, L; Pozgayová, S; Kupcová, V; Durínová, S

2006-06-01

Hereditary hemochromatosis is considered one of the most common hereditary diseases in population of Caucasian origin. In recent years, a candidate gene for HLA-linked hemochromatosis, HFE, has been cloned, and a single G-to-A mutation resulting in a cysteine-to-tyrosine substitution (C282Y) has been identified in up to 80% of study patients with type 1 hereditary hemochromatosis. The purpose of the paper was to confirm the importance of genetic testing for HFE mutations in making the diagnosis of hemochromatosis and find out a suitable diagnostic algorithm for the indication of this form of diagnostics in patients suspected of hereditary hemochromatosis. The examination of C282Y mutation was conducted in 500 subjects. The most frequent indications for DNA analysis were hepatopathy of unknown ethiology, liver cirrhosis, diabetes mellitus, bronze skin pigmentation in connection with high serum iron concentration, elevated transferrin saturation and elevated serum ferritin levels. In our group of patients, 29 homozygotes and 75 heterozygotes for C282Y mutation were identified, 10 patients carried both C282Y and H63D mutations of HFE gene (compound heterozygotes), whereas in 386 subjects the mutation was not found. The genotype-phenotype correlation showed that 22 homozygotes had liver affection proved by imaging and/or histologic methods. Except the liver disorders, the most common symptoms of these patients were type 2 diabetes mellitus or glucose tolerance disorder (10 patients), arthritis or joint pain (9 patients) and cardiovascular disorders, such as cardiomyopathy (2 patients). Bronze skin pigmentation was present in 9 homozygotes. Transferin saturation values were significantly higher in homozygotes for C282Y mutation as compared to C282Y heterozygotes (p diagnostics of this severe, but in early recognition curable disease. Early detection and phlebotomy treatment prior to the onset of cirrhosis can reduce morbidity and normalize life expectancy. It is readily

Two Siblings Followed Up for Hereditary Multiple Exostoses

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Meltem Erol

2014-06-01

Full Text Available Hereditary multiple exostoses is an autosomal dominant disease with abnormal bone formation especially at the long bones. Osteochondromas, which occur in the course of the disease, can cause growth disturbances in affected children. Due to pressure effects of osteochondromas, compression of vessels, nerves and tendons, restriction of joint motion, and neurologic compromise as well as painful local symptoms can be seen. Here, we aimed to present two siblings who had generalized pain and swelling in different parts of the body. We detected multiple osteochondromas in different parts of their bodies, especially at the long bones. Our patients had painful local symptoms. There was no growth retardation, but the presence of many osteochondromas led us to contemplate that it was serious form of the disease. Their father had lesser number of osteochondromas. In this paper, we aimed to emphasize the necessity of close follow-up for the risk of malignant transformation of osteochondromas. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 116-9

Multiple Hereditary Osteochondromatosis: A Case Report

OpenAIRE

K???kesmen, ?i?dem; ?zen, Bu?ra; Ak?am, Mustafa

2007-01-01

Objectives Common carious lesions owing to vomiting are not widespread in children. In this case, we aimed to report an 11-years-old male patient with common carious lesions due to repeated vomitings, chewing and eating difficulty and retarded growth with Multiple Hereditary Osteochondromatosis (MHO). Case Report An 11-years-old boy was referred to Department of Pediatric Dentistry in Faculty of Dentistry because of eating difficulty owing to common carious lesions. It was seen that the patie...

Current problems in haematology. 2: Hereditary spherocytosis.

OpenAIRE

Smedley, J C; Bellingham, A J

1991-01-01

Hereditary spherocytosis is a relatively common haematological disorder and will be encountered by all haematologists. The abundance of new information, dealing principally with molecular and genetic aspects of pathophysiology, is beginning to have implications for its investigation and management. While these advances have not yet exerted a large influence at therapeutic level, the promise of such advents as prenatal diagnosis make this an exciting field to watch.

Multimodality imaging features of hereditary multiple exostoses

OpenAIRE

Kok, H K; Fitzgerald, L; Campbell, N; Lyburn, I D; Munk, P L; Buckley, O; Torreggiani, W C

2013-01-01

Hereditary multiple exostoses (HME) or diaphyseal aclasis is an inherited disorder characterised by the formation of multiple osteochondromas, which are cartilage-capped osseous outgrowths, and the development of associated osseous deformities. Individuals with HME may be asymptomatic or develop clinical symptoms, which prompt imaging studies. Different modalities ranging from plain radiographs to cross-sectional and nuclear medicine imaging studies can be helpful in the diagnosis and detecti...

Hereditary Portfolio Optimization with Taxes and Fixed Plus Proportional Transaction Costs—Part II

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Mou-Hsiung Chang

2007-01-01

Full Text Available This paper is the continuation of the paper entitled “Hereditary portfolio optimization with taxes and fixed plus proportional transaction costs I” that treats an infinite-time horizon hereditary portfolio optimization problem in a market that consists of one savings account and one stock account. Within the solvency region, the investor is allowed to consume from the savings account and can make transactions between the two assets subject to paying capital-gain taxes as well as a fixed plus proportional transaction cost. The investor is to seek an optimal consumption-trading strategy in order to maximize the expected utility from the total discounted consumption. The portfolio optimization problem is formulated as an infinite dimensional stochastic classical impulse control problem due to the hereditary nature of the stock price dynamics and inventories. This paper contains the verification theorem for the optimal strategy. It also proves that the value function is a viscosity solution of the QVHJBI.

Surgical treatment of hereditary lens subluxations.

Science.gov (United States)

Ozdek, Sengul; Sari, Ayca; Bilgihan, Kamil; Akata, Fikret; Hasanreisoglu, Berati

2002-01-01

To evaluate the effectiveness and results of pars plana vitreolensectomy approach with transscleral fixation of intraocular lens in hereditary lens subluxations. Fifteen eyes of 9 consecutive patients with a mean age of 12.8+/-6.2 years (6-26 years) with hereditary lens subluxation were operated on and the results were evaluated in a prospective study. Surgery was considered if best spectacle corrected visual acuity (BSCVA) was less than 20/70. All eyes underwent a 2-port pars plana vitreolensectomy and transscleral fixation of an intraocular lens (IOL). The mean follow-up period was 12.6+/-7.5 months (6-22 months). There was no major intraoperative complication. Preoperatively, 8 eyes (53.3%) had a BSCVA of counting fingers (CF) and 7 eyes (46.6%) had a BSCVA of 20/200 to 20/70. Postoperatively, 14 eyes (93.3%) had a BSCVA of 20/50 or better. None of the patients had IOL decentration or intraocular pressure (IOP) increase during the follow-up period. There was a macular hole formation in 1 eye postoperatively. The early results of pars plana vitreolensectomy with IOL implantation using scleral fixation technique had shown that it not only promises a rapid visual rehabilitation but it is also a relatively safe method. More serious complications, however, may occur in the long term.

Motor activation in SPG4-linked hereditary spastic paraplegia

DEFF Research Database (Denmark)

Scheuer, KH; Nielsen, JE; Krabbe, Katja

2006-01-01

OBJECTIVE: The aim of this study was to investigate the extent of motor cortical functional reorganisation in patients with SPG4-linked hereditary spastic paraplegia by exploring cortical motor activation related to movements of clinically affected (lower) and unaffected (upper) limbs. METHODS: T...

Impaired Mitochondrial Dynamics Underlie Axonal Defects in Hereditary Spastic Paraplegias.

Science.gov (United States)

Denton, Kyle; Mou, Yongchao; Xu, Chong-Chong; Shah, Dhruvi; Chang, Jaerak; Blackstone, Craig; Li, Xue-Jun

2018-05-02

Mechanisms by which long corticospinal axons degenerate in hereditary spastic paraplegia (HSP) are largely unknown. Here, we have generated induced pluripotent stem cells (iPSCs) from patients with two autosomal recessive forms of HSP, SPG15 and SPG48, which are caused by mutations in the ZFYVE26 and AP5Z1 genes encoding proteins in the same complex, the spastizin and AP5Z1 proteins, respectively. In patient iPSC-derived telencephalic glutamatergic and midbrain dopaminergic neurons, neurite number, length and branching are significantly reduced, recapitulating disease-specific phenotypes. We analyzed mitochondrial morphology and noted a significant reduction in both mitochondrial length and their densities within axons of these HSP neurons. Mitochondrial membrane potential was also decreased, confirming functional mitochondrial defects. Notably, mdivi-1, an inhibitor of the mitochondrial fission GTPase DRP1, rescues mitochondrial morphology defects and suppresses the impairment in neurite outgrowth and late-onset apoptosis in HSP neurons. Furthermore, knockdown of these HSP genes causes similar axonal defects, also mitigated by treatment with mdivi-1. Finally, neurite outgrowth defects in SPG15 and SPG48 cortical neurons can be rescued by knocking down DRP1 directly. Thus, abnormal mitochondrial morphology caused by an imbalance of mitochondrial fission and fusion underlies specific axonal defects and serves as a potential therapeutic target for SPG15 and SPG48.

Iron in hereditary retinal degeneration: PIXE microanalysis Preliminary results

International Nuclear Information System (INIS)

Sergeant, C.; Gouget, B.; Llabador, Y.; Simonoff, M.; Yefimova, M.; Courtois, Y.; Jeanny, J.C.

1999-01-01

Several types of hereditary retinal degeneration with progressive alteration of photoreceptors exist in men and animals. Recent immunohistochemical results have shown strong degradation of transferrin, the protein responsible for iron transport, in retinas of rats with hereditary retinal degeneration. Freeze-dried thin sections of rat retinas from different stages of the disease, and respective coeval control sections, have been analyzed using nuclear microprobe. In this first part of the study, the rat retinas at post-natal stages of 35 and 45 days have been analyzed. The sample preparation and the post-irradiation staining to determine precisely the retinal layers involved are described. Preliminary results of element distributions (K, Ca, Fe) in the rat retina layers are discussed. A very high content of calcium in the choriocapillaris of dystrophic rat retinas was observed. Preliminary results on iron distribution in the rat retina layers are presented

Ethical, social and counselling issues in hereditary cancer susceptibility.

Science.gov (United States)

Garber, J E; Patenaude, A F

1995-01-01

Genetic testing for hereditary susceptibility to disease is new. Much has been learned from experience with Huntington's disease and other non-malignant conditions. There are some differences in the case of predisposition testing for cancer: there is often the perception that cancer is preventable and sometimes curable, in contrast to other hereditary conditions. Testing raises many issues new to the medical community and to the public as well. There is great concern that the explosive technology be used responsibly, so that the potential benefits of genetic knowledge are not eclipsed by the risks to autonomy, privacy and justice. Practical concerns about insurability and discrimination may inhibit some at risk individuals from taking advantage of this powerful technology. There has been considerable effort already in the UK, Europe and the USA at the research and social levels to create protection for individuals found to carry genetic susceptibility to disease.

Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2

NARCIS (Netherlands)

Züchner, Stephan; de Jonghe, Peter; Jordanova, Albena; Claeys, Kristl G.; Guergueltcheva, Velina; Cherninkova, Sylvia; Hamilton, Steven R.; van Stavern, Greg; Krajewski, Karen M.; Stajich, Jeffery; Tournev, Ivajlo; Verhoeven, Kristien; Langerhorst, Christine T.; de Visser, Marianne; Baas, Frank; Bird, Thomas; Timmerman, Vincent; Shy, Michael; Vance, Jeffery M.

2006-01-01

OBJECTIVE: Charcot-Marie-Tooth (CMT) neuropathy with visual impairment due to optic atrophy has been designated as hereditary motor and sensory neuropathy type VI (HMSN VI). Reports of affected families have indicated autosomal dominant and recessive forms, but the genetic cause of this disease has

Hereditary hemochromatosis and risk of ischemic heart disease

DEFF Research Database (Denmark)

Ellervik, Christina; Tybjaerg-Hansen, Anne; Grande, Peer

2005-01-01

BACKGROUND: We tested the hypothesis that the hereditary hemochromatosis genotypes C282Y/C282Y, C282Y/H63D, or C282Y/wild-type are risk factors for ischemic heart disease (IHD) and myocardial infarction (MI). METHODS AND RESULTS: We performed a prospective study of 9178 individuals from the Danish...

Suspected Perinatal Depression Revealed to be Hereditary Diffuse Leukoencephalopathy with Spheroids.

Science.gov (United States)

Blume, Josefine; Weissert, Robert

2017-01-01

Early motor symptoms of neurodegenerative diseases often appear in combination with psychiatric symptoms, such as depression or personality changes, and are in danger of being misdiagnosed as psychogenic in young patients. We present the case of a 32-year-old woman who presented with rapid-onset depression, followed by a hypokinetic movement disorder and cognitive decline during pregnancy. Genetic testing revealed a mutation in the colony-stimulating factor 1 receptor gene, which led to the diagnosis of hereditary diffuse leukoencephalopathy with spheroids. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is probably an under-recognized disease. HDLS should be considered in patients with rapidly progressing parkinsonian symptoms and dementia accompanied by white matter lesions.

Suspected Perinatal Depression Revealed to be Hereditary Diffuse Leukoencephalopathy with Spheroids

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Josefine Blume

2017-01-01

Full Text Available Early motor symptoms of neurodegenerative diseases often appear in combination with psychiatric symptoms, such as depression or personality changes, and are in danger of being misdiagnosed as psychogenic in young patients. We present the case of a 32-year-old woman who presented with rapid-onset depression, followed by a hypokinetic movement disorder and cognitive decline during pregnancy. Genetic testing revealed a mutation in the colony-stimulating factor 1 receptor gene, which led to the diagnosis of hereditary diffuse leukoencephalopathy with spheroids. Hereditary diffuse leukoencephalopathy with spheroids (HDLS is probably an under-recognized disease. HDLS should be considered in patients with rapidly progressing parkinsonian symptoms and dementia accompanied by white matter lesions.

SPG20 mutation in three siblings with familial hereditary spastic paraplegia.

Science.gov (United States)

Dardour, Leila; Roelens, Filip; Race, Valerie; Souche, Erika; Holvoet, Maureen; Devriendt, Koen

2017-07-01

Troyer syndrome (MIM#275900) is an autosomal recessive form of complicated hereditary spastic paraplegia. It is characterized by progressive lower extremity spasticity and weakness, dysarthria, distal amyotrophy, developmental delay, short stature, and subtle skeletal abnormalities. It is caused by deleterious mutations in the SPG20 gene, encoding spartin, on Chromosome 13q13. Until now, six unrelated families with a genetically confirmed diagnosis have been reported. Here we report the clinical findings in three brothers of a consanguineous Moroccan family, aged 24, 17, and 7 yr old, with spastic paraplegia, short stature, motor and cognitive delay, and severe intellectual disability. Targeted exon capture and sequencing showed a homozygous nonsense mutation in the SPG20 gene, c.1369C>T (p.Arg457*), in the three affected boys. © 2017 Dardour et al.; Published by Cold Spring Harbor Laboratory Press.

On the many faces of Leber hereditary optic neuropathy

NARCIS (Netherlands)

Oostra, RJ; Tijmes, NT; Cobben, JM; Bolhuis, PA; vanNesselrooij, BPM; Houtman, WA; deKokNazaruk, MM; BleekerWagemakers, EM

Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between

On the many faces of Leber hereditary optic neuropathy

NARCIS (Netherlands)

Oostra, R. J.; Tijmes, N. T.; Cobben, J. M.; Bolhuis, P. A.; van Nesselrooij, B. P.; Houtman, W. A.; de Kok-Nazaruk, M. M.; Bleeker-Wagemakers, E. M.

1997-01-01

Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder, associated with mutations in the mitochondrial DNA, which is notorious for its aspecific presentations. Two pedigrees are described with cases that are atypical for LHON with respect to sex, age of onset, interval between

Study of glycolytic intermediates in hereditary elliptocytosis with thalassemia

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Pavri Roshan

1977-01-01

Full Text Available Glycolytic intermediates like ATP, DPG and GSH have been studied in a family with. hereditary elliptocytosis and thalassemia. Results indicate a fall in ATP with a concomitant rise in DPG in the Patient. Findings are discussed in relation to other data.

Association of hereditary elliptocytosis and Gilbert’s syndrome as the cause of biliary calculosis: Case report

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Radlović Nedeljko

2011-01-01

Full Text Available Introduction. Biliary calculosis is rare in children. It occurs associated with different haemolytic and non-haemolytic disorders, which are sometimes also combined. Case Outline. A 15-year-old male was hospitalized due to biliary calculosis and non-conjugated hyper-bilirubinemia. A mild non-conjugated hyperbilirubinemia, without anaemia and other symptoms of liver dysfunction, was registered at age 8 years, and 7 years later cholelithiasis with transitory choledocholithiasis. The finding of ellyptocytes in blood smear, which was also verified in mother, normal haemoglobin count and the absence of diseases followed by secondary dysmorphic erythrocytes of this type, indicated a clinically milder (compensated hereditary ellyptocytosis, while more than a double increase of non-conjugated serum bilirubin fracture after a three-day hypocaloric diet (400 kcal per day showed the concurrent presence of Gilbert’s syndrome. In the laparascopically removed gallbladder a larger number of small pigmented calculi were disclosed. Conclusion. Gilbert’s syndrome is an essential precipitating factor of biliary calculosis in patients with chronic haemolytic condition. Thus, in all cases of biliary calculosis and non-conjugated hyperbilirubinemia with absent clinical and laboratory parameters of liver disorders and anaemia, except in compensated haemolytic disease and Gilbert’s syndrome as isolated disorders, a possibility of their association should be taken into consideration.

A novel ABCD1 mutation detected by next generation sequencing in presumed hereditary spastic paraplegia: A 30-year diagnostic delay caused by misleading biochemical findings.

Science.gov (United States)

Koutsis, Georgios; Lynch, David S; Tucci, Arianna; Houlden, Henry; Karadima, Georgia; Panas, Marios

2015-08-15

To present a Greek family in which 5 male and 2 female members developed progressive spastic paraplegia. Plasma very long chain fatty acids (VLCFA) were reportedly normal at first testing in an affected male and for over 30 years the presumed diagnosis was hereditary spastic paraplegia (HSP). Targeted next generation sequencing (NGS) was used as a further diagnostic tool. Targeted exome sequencing in the proband, followed by Sanger sequencing confirmation; mutation segregation testing in multiple family members and plasma VLCFA measurement in the proband. NGS of the proband revealed a novel frameshift mutation in ABCD1 (c.1174_1178del, p.Leu392Serfs*7), bringing an end to diagnostic uncertainty by establishing the diagnosis of adrenomyeloneuropathy (AMN), the myelopathic phenotype of X-linked adrenoleukodystrophy (ALD). The mutation segregated in all family members and the diagnosis of AMN/ALD was confirmed by plasma VLCFA measurement. Confounding factors that delayed the diagnosis are presented. This report highlights the diagnostic utility of NGS in patients with undiagnosed spastic paraplegia, establishing a molecular diagnosis of AMN, allowing proper genetic counseling and management, and overcoming the diagnostic delay that can be rarely caused by false negative VLCFA analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

Hereditary arrhythmias and cardiomyopathies: decision-making about genetic testing.

Science.gov (United States)

Louis, Clauden; Calamaro, Emily; Vinocur, Jeffrey M

2018-01-01

The modern field of clinical genetics has advanced beyond the traditional teachings familiar to most practicing cardiologists. Increased understanding of the roles of genetic testing may improve uptake and appropriateness of use. Clinical genetics has become integral to the management of patients with hereditary arrhythmia and cardiomyopathy diagnoses. Depending on the condition, genetic testing may be useful for diagnosis, prognosis, treatment, family screening, and reproductive planning. However, genetic testing is a powerful tool with potential for underuse, overuse, and misuse. In the absence of a substantial body of literature on how these guidelines are applied in clinical practice, we use a case-based approach to highlight key lessons and pitfalls. Importantly, in many scenarios genetic testing has become the standard of care supported by numerous class I recommendations; genetic counselors can improve accessibility to and appropriate use and application of testing. Optimal management of hereditary arrhythmias and cardiomyopathies incorporates genetic testing, applied as per consensus guidelines, with involvement of a multidisciplinary team.

Total Hip Arthroplasty Using a Polished Tapered Cemented Stem in Hereditary Multiple Exostosis

Science.gov (United States)

Kanda, Akio; Kaneko, Kazuo; Obayashi, Osamu; Mogami, Atsuhiko

2016-01-01

A 61-year-old Japanese man underwent right total hip arthroplasty for hereditary multiple exostosis. At first presentation, he had suffered from coxalgia for a long time. On radiographic images, there was a gigantic femoral head, increased shaft angle, and large diameter of the femoral neck. He had also developed coxarthrosis and severe pain of the hip joint. The transformation of the proximal femur bone causes difficulty in setting a cementless total hip prosthesis. Therefore, total hip arthroplasty using a cemented polished tapered stem was performed via a direct lateral approach. Using a cemented polished tapered stem allowed us to deal with the femoral bone transformation and bone substance defectiveness due to exostosis and also minimized the invasiveness of the operation. PMID:27127668

Four novel germline mutations in the MLH1 and PMS2 mismatch repair genes in patients with hereditary nonpolyposis colorectal cancer.

Science.gov (United States)

Montazer Haghighi, Mahdi; Radpour, Ramin; Aghajani, Katayoun; Zali, Narges; Molaei, Mahsa; Zali, Mohammad Reza

2009-08-01

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common cause of early onset hereditary colorectal cancer. In the majority of HNPCC families, microsatellite instability (MSI) and germline mutation in one of the DNA mismatch repair (MMR) genes are found. The entire coding sequence of MMR genes (MLH1, MLH2, MLH6, and PMS2) was analyzed using direct sequencing. Also, tumor tests were done as MSI and immunohistochemistry testing. We were able to find three novel MLH1 and one novel PMS2 germline mutations in three Iranian HNPCC patients. The first was a transversion mutation c.346A>C (T116P) and happened in the highly conserved HATPase-c region of MLH1 protein. The second was a transversion mutation c.736A>T (I246L), which caused an amino acid change of isoleucine to leucine. The third mutation (c.2145,6 delTG) was frameshift and resulted in an immature stop codon in five codons downstream. All of these three mutations were detected in the MLH1 gene. The other mutation was a transition mutation, c.676G>A (G207E), which has been found in exon six of the PMS2 gene and caused an amino acid change of glycine to glutamic acid. MSI assay revealed high instability in microsatellite for two patients and microsatellite stable for one patient. In all patients, an abnormal expression of the MMR proteins in HNPCC was related to the above novel mutations.

Development and validation of a 36-gene sequencing assay for hereditary cancer risk assessment

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Valentina S. Vysotskaia

2017-02-01

Full Text Available The past two decades have brought many important advances in our understanding of the hereditary susceptibility to cancer. Numerous studies have provided convincing evidence that identification of germline mutations associated with hereditary cancer syndromes can lead to reductions in morbidity and mortality through targeted risk management options. Additionally, advances in gene sequencing technology now permit the development of multigene hereditary cancer testing panels. Here, we describe the 2016 revision of the Counsyl Inherited Cancer Screen for detecting single-nucleotide variants (SNVs, short insertions and deletions (indels, and copy number variants (CNVs in 36 genes associated with an elevated risk for breast, ovarian, colorectal, gastric, endometrial, pancreatic, thyroid, prostate, melanoma, and neuroendocrine cancers. To determine test accuracy and reproducibility, we performed a rigorous analytical validation across 341 samples, including 118 cell lines and 223 patient samples. The screen achieved 100% test sensitivity across different mutation types, with high specificity and 100% concordance with conventional Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA. We also demonstrated the screen’s high intra-run and inter-run reproducibility and robust performance on blood and saliva specimens. Furthermore, we showed that pathogenic Alu element insertions can be accurately detected by our test. Overall, the validation in our clinical laboratory demonstrated the analytical performance required for collecting and reporting genetic information related to risk of developing hereditary cancers.

Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management.

Science.gov (United States)

Papadopoulos, Nikolaos; Argiana, Vasiliki; Deutsch, Melanie

2018-01-01

Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%.

SPG10 is a rare cause of spastic paraplegia in European families.

NARCIS (Netherlands)

Schule, R.; Kremer, H.P.H.; Kassubek, J.; Auer-Grumbach, M.; Kostic, V.; Klopstock, T.; Klimpe, S.; Otto, S.; Boesch, S.; Warrenburg, B.P.C. van de; Schols, L.

2008-01-01

BACKGROUND: SPG10 is an autosomal dominant form of hereditary spastic paraplegia (HSP), which is caused by mutations in the neural kinesin heavy chain KIF5A gene, the neuronal motor of fast anterograde axonal transport. Only four mutations have been identified to date. OBJECTIVE: To determine the

SPG10 is a rare cause of spastic paraplegia in European families

NARCIS (Netherlands)

Schuele, R.; Kremer, B. P. H.; Kassubek, J.; Auer-Grumbach, M.; Kostic, V.; Klopstock, T.; Klimpe, S.; Otto, S.; Boesch, S.; van de Warrenburg, B. P.; Schoels, L.

Background: SPG10 is an autosomal dominant form of hereditary spastic paraplegia (HSP), which is caused by mutations in the neural kinesin heavy chain KIF5A gene, the neuronal motor of fast anterograde axonal transport. Only four mutations have been identified to date. Objective: To determine the

Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST mimicking hereditary GIST syndromes

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Mafalda Costa Neves

2015-01-01

Conclusion: We describe a diffuse form of sporadic ICC hyperplasia harbouring multifocal GISTs, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes. Detection of somatic c-KIT exon 11 mutation ruled out a hereditary disorder.

Severe fatigue and reduced quality of life in children with hereditary motor and sensory neuropathy 1A

NARCIS (Netherlands)

Jagersma, Elbrich; Jeukens-Visser, Martine; van Paassen, Barbara W.; Meester-Delver, Anke; Nollet, Frans

2013-01-01

Severe fatigue and low quality of life are reported by a majority of adult patients with hereditary motor and sensory neuropathy 1A. In children with hereditary motor and sensory neuropathy 1A, the prevalence and impact of fatigue have not been studied yet. In this questionnaire survey, 55 Dutch

Mania associated with complicated hereditary spastic paraparesis

OpenAIRE

Raghavendra B Nayak; Govind S Bhogale; Nanasaheb M Patil; Aditya A Pandurangi

2011-01-01

Hereditary spastic paraparesis (HSP) is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints ...

Disabilities caused by unstable mutations in Costa Rica

OpenAIRE

Morales Montero, Fernando; Cuenca Berger, Patricia; Castro Volio, Isabel

2004-01-01

Myotonic dystrophy and fragile X syndrome are two genetically determined relatively common disabilities. Both are examples of a new type of mutation mechanism called unstable or dynamic mutations, triple repeats expansions or DNA amplification. Fragile X syndrome is recognized as the main cause of hereditary mental retardation and myotonic dystrophy is considered the most common muscular dystrophy of adults. This is a prospective non randomized study of clinically affected people,...

Cerebral Vein Thrombosis:Screening of Acquired and Hereditary Thrombophilic Risk Factors

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Sarraf Payam

2009-10-01

Full Text Available Cerebral vein thrombosis (CVT is an infrequent condition with a large variety of causes that can lead to serious disabilities. However, in 20% to 35% of cases, no cause is found. In this study we evaluated the hereditary (P & C Proteins, antithrombin, mutation of prothrombin G20210A and factor V Leiden, other risk factors (hyperhomocycteinemia, factor VIII, ACL-ab, APL-ab, and OCP and clinical manifestations among a population of Iranian patients with CVT. 18 women and 10 men aged 16 to 50 years with CVT were screened for inherited and acquired coagulation risk factors. No one had an abnormal ACL-ab, APL-ab or antithrombin III deficiency. One had prothrombin G20210A mutation (heterozygot (3.6%. Hyperhomocycteinemia was observed in 5 patients (17.9%. APC-R was decreased in 3 (10.7%. 2 had positive factor V Leiden mutation (heterozygot (7.1%. 17 had an increased of factor VIII (60.7. PS and PC deficiencies were each detected in two cases (7.1%. Conclusion: Our study suggests that screening for inherited thrombophilia may be an integral part in the diagnostic workup and duration of treatment in patients with CVT.

Friedreich's ataxia mimicking hereditary motor and sensory neuropathy.

Science.gov (United States)

Panas, Marios; Kalfakis, Nikolaos; Karadima, Georgia; Davaki, Panagiota; Vassilopoulos, Demetris

2002-11-01

Four patients from three unrelated families, with clinical and electrophysiological findings compatible with the diagnosis of hereditary motor and sensory neuropathy, are presented. The molecular analysis showed that the affected individuals were homozygous for the mutation in the X25 gene, characteristic of Friedreich's ataxia. These patients seem to represent a form of Friedreich's ataxia mimicking Charcot-Marie-Tooth disease.

Hereditary spastic paraplegia.

Science.gov (United States)

Blackstone, Craig

2018-01-01

The hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurologic disorders with the common feature of prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. The HSPs exist not only in "pure" forms but also in "complex" forms that are associated with additional neurologic and extraneurologic features. The HSPs are among the most genetically diverse neurologic disorders, with well over 70 distinct genetic loci, for which about 60 mutated genes have already been identified. Numerous studies elucidating the molecular pathogenesis underlying HSPs have highlighted the importance of basic cellular functions - especially membrane trafficking, mitochondrial function, organelle shaping and biogenesis, axon transport, and lipid/cholesterol metabolism - in axon development and maintenance. An encouragingly small number of converging cellular pathogenic themes have been identified for the most common HSPs, and some of these pathways present compelling targets for future therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

Brain abscesses and hereditary hemorrhagic telangiectasia

International Nuclear Information System (INIS)

Vives, Daniel A.; Bauni, Carlos E.; Mendoza, Monica E.

2003-01-01

Rendu-Osler-Weber disease or Hereditary Hemorrhagic Telangiectasia (HHT) is a generalized familial angiodysplastic disorder. The neurological manifestations of this entity are due to Central Nervous System vascular lesions or to complications of other visceral lesions such as pulmonary arteriovenous fistulae. This report describes two patients (males, 40 and 61 years old), with brain abscesses associated with HHT. The CT, MRI and Angiographic findings as well as the therapeutic approach are analyzed. Patients with brain abscess of unknown origin must be evaluated for the presence of lung vascular malformation in association with HHT. (author)

Bone scintigraphy in hereditary multiple exostoses

International Nuclear Information System (INIS)

Epstein, D.A.; Levin, E.J.

1978-01-01

Two adult patients with multiple hereditary exostoses, a skeletal disorder with recognized malignant potential, each demonstrated increased /sup 99m/Tc diphosphonate uptake in an exostosis in which renewed growth had begun. None of the other multiple exostoses in either patient showed abnormal uptake. Histologic study of the lesions demonstrated chondrosarcoma in one case and benign osteochondroma in the second. Although bone scintigraphy nonspecifically identifies bone growth rather than malignant degeneration, it is more useful than radiographic bone survey in the periodic surveillance of adult patients with this disorder

Alterations of red blood cell metabolome in overhydrated hereditary stomatocytosis.

NARCIS (Netherlands)

Darghouth, D.; Koehl, B.; Heilier, J.F.; Madalinski, G.; Bovee, P.H.; Bosman, G.J.C.G.M.; Delaunay, J.; Junot, C.; Romeo, P.H.

2011-01-01

Overhydrated hereditary stomatocytosis, clinically characterized by hemolytic anemia, is a rare disorder of the erythrocyte membrane permeability to monovalent cations, associated with mutations in the Rh-associated glycoprotein gene. We assessed the red blood cell metabolome of 4 patients with this

The neuropathology of hereditary congenital facial palsy vs Mobius syndrome.

NARCIS (Netherlands)

Verzijl, H.T.F.M.; Zwaag, B. van der; Lammens, M.M.Y.; Donkelaar, H.J. ten; Padberg, G.W.A.M.

2005-01-01

OBJECTIVE: To characterize the neuropathology of hereditary congenital facial palsy. METHODS: The authors compared brainstem pathology of three members of one family with autosomal dominant congenital facial palsy to that in three age-matched controls. The neuropathologic findings of the familial

Mutations found in the Danish population causing Hereditary Hemorrhagic Telangiectasia

DEFF Research Database (Denmark)

Tørring, Pernille M; Brusgaard, Klaus

2011-01-01

University Hospital, Denmark HHT is an autosomal vascular disorder caused by mutations of either of three loci ENG, ACVLR1 or MADH4. HHT is characterised by recurrent nosebleeds, mucocutaneous telangiectases, and more severe visceral malformations. During the last decade the Danish HHT centre has...

Intragenic duplication: a novel mutational mechanism in hereditary pancreatitis

DEFF Research Database (Denmark)

Joergensen, Maiken T; Geisz, Andrea; Brusgaard, Klaus

2011-01-01

In a hereditary pancreatitis family from Denmark, we identified a novel intragenic duplication of 9 nucleotides in exon-2 of the human cationic trypsinogen (PRSS1) gene (c.63_71dup) which at the amino-acid level resulted in the insertion of 3 amino acids within the activation peptide of cationic...

Hereditary spastic paraplegia caused by the PLP1 'rumpshaker mutation'

DEFF Research Database (Denmark)

Svenstrup, Kirsten; Giraud, Geneviève; Boespflug-Tanguy, Odile

2010-01-01

with the 'rumpshaker mutation.' PATIENTS: A family with HSP caused by the 'rumpshaker mutation.' RESULTS: The patients showed nystagmus during infancy and had early onset of HSP. They had normal cognition, and cerebral MRI showed relatively unspecific white matter abnormalities on T2 sequences without clear...

Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations.

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Sofie V Nielsen

2017-04-01

Full Text Available Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often do not provide direct mechanistic insight. Here we demonstrate, for the first time, that saturation mutagenesis, biophysical modeling and co-variation analysis, performed in silico, can predict the abundance, metabolic stability, and function of proteins inside living cells. As a model system, we selected the human mismatch repair protein, MSH2, where missense variants are known to cause the hereditary cancer predisposition disease, known as Lynch syndrome. We show that the majority of disease-causing MSH2 mutations give rise to folding defects and proteasome-dependent degradation rather than inherent loss of function, and accordingly our in silico modeling data accurately identifies disease-causing mutations and outperforms the traditionally used genetic disease predictors. Thus, in conclusion, in silico biophysical modeling should be considered for making genotype-phenotype predictions and for diagnosis of Lynch syndrome, and perhaps other hereditary diseases.

Coinheritance of hereditary spherocytosis and reversibility of cirrhosis in a young female patient with hereditary hemochromatosis.

Science.gov (United States)

Höblinger, A; Erdmann, C; Strassburg, C P; Sauerbruch, T; Lammert, F

2009-04-16

Here we report a 33-years-old woman with hereditary spherocytosis and hemochromatosis due to homozygosity for the C282Y mutation of the HFE gene. The coinheritance of both conditions led to severe iron overload and liver cirrhosis at young age. The patient was treated by repeated phlebotomy, and reversibility of cirrhosis was documented by transient elastography. This report discusses the pathophysiology of iron accumulation in patients with hemolytic anemia combined with HFE C282Y homozygosity. The case indicates that patients with hematological disorders characterized by increased erythropoetic activity should be screened for HFE mutations.

[Molecular genetic analysis and clinical aspects of patients with hereditary hemochromatosis].

Science.gov (United States)

Lange, U; Teichmann, J; Dischereit, G

2014-08-01

The purpose of the study was to perform a molecular genetic analysis and to document clinical aspects in patients with hereditary hemochromatosis. The study included 33 outpatients (23 males average age 50.6 years and 10 females average age 60.6 years) with a disorder of iron metabolism (transferrin saturation > 75 %) as confirmation of hemochromatosis who were subjected to molecular genetic and clinical analyses. A homozygous mutation of the hemochromatosis (HFE) gene (C282YY) was detected in 63.6 %, a compound heterozygous mutation (C282Y/H63D) in 30.3% and no mutation of the HFE gene was detected in 6.1 %. The following organ manifestations could be objectified: arthralgia (78.8 %), liver disease (39.9 %), skin hyperpigmentation (30.3 %), osteoporosis (24.2 %), diabetes mellitus (24.2 %) and cardiomyopathy (12.1 %). Comparison between patients with heterozygous and homozygous hemochromatosis revealed the following differences: compound heterozygote patients presented less frequently with osteoarthritis of the metacarpophalangeal (MCP) joints and hands (85.7 %/71.4 % homozygotes vs. 60 %/60 % heterozygotes). Osteoarthritis of the shoulder joints and osteoporosis as well as hypothyroidism were more frequent in compound heterozygote patients, whereas osteoarthritis of the knee and hip joints as well as liver disease were more common in homozygote patients. No differences between both groups were seen with respect to the clinical manifestations of cardiomyopathy and diabetes mellitus. Prevalent causes of death in hereditary hemochromatosis are heart failure, liver disease (cirrhosis and hepatocellular carcinoma) and portal hypertension. Therefore, an early diagnosis, adequate therapy and genetic screening of family members are of great importance. Medicinal treatment will only effectively prevent deleterious organ involvement and subsequent complications if initiated at an early stage. Furthermore, an overview of the current data is given.

Functional and Structural Changes in a Canine Model of Hereditary Primary Angle-Closure Glaucoma

Science.gov (United States)

Kecova, Helga; Harper, Matthew M.; Nilaweera, Wijitha; Kuehn, Markus H.; Kardon, Randy H.

2010-01-01

Purpose. To characterize functional and structural changes in a canine model of hereditary primary angle-closure glaucoma. Methods. Intraocular pressure (IOP) was evaluated with tonometry in a colony of glaucomatous dogs at 8, 15, 18, 20, and 30 months of age. Retinal function was evaluated using electroretinography (scotopic, photopic, and pattern). Examination of anterior segment structures was performed using gonioscopy and high-frequency ultrasonography (HFU). Results. A gradual rise in IOP was observed with an increase in age: 8 months, 14 mm Hg (median value); 15 months, 15.5 mm Hg; 18 months, 17.5 mm Hg; 20 months, 24 mm Hg; 30 months, 36 mm Hg. Provocative testing with mydriatic agents (tropicamide and atropine 1%) caused significant increases in IOP (35% and 50%, respectively). HFU analysis showed complete collapse of iridocorneal angles by 20 months of age. Scotopic and photopic ERG analysis did not reveal significant deficits, but pattern ERG analysis showed significantly reduced amplitudes in glaucomatous dogs (glaucoma, 3.5 ± 0.4 μV; control, 6.2 ± 0.3 μV; P = 0.004; Student's t-test). Histologic analysis revealed collapse of the iridocorneal angle, posterior bowing of the lamina cribrosa, swelling and loss of large retinal ganglion cells, increased glial reactivity, and increased thickening of the lamina cribrosa. Conclusions. Canine hereditary angle-closure glaucoma is characterized by a progressive increase in intraocular pressure, loss of optic nerve function, and retinal ganglion cell loss. PMID:19661222

Intronic deletions in the SLC34A3 gene: A cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria

OpenAIRE

Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R.; Gray, Amie K.; Baluarte, H. Jorge; Econs, Michael J.

2013-01-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6 ½-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24- hour urine cal...

Hereditary non-polyposis colorectal cancer/Lynch syndrome in three dimensions.

Science.gov (United States)

Kravochuck, Sara E; Church, James M

2017-12-01

Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing. Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry. There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC. Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance. © 2016 Royal Australasian College of Surgeons.

Clinical and genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer families

OpenAIRE

Wang, Xu-Lin; Yuan, Ying; Zhang, Su-Zhan; Cai, Shan-Rong; Huang, Yan-Qin; Jiang, Qiang; Zheng, Shu

2006-01-01

AIM: To analyze the clinical characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to screen the germline mutations of human mismatch repair genes hMLH1 and hMSH2 in the probands.

RB1 mutations and second primary malignancies after hereditary retinoblastoma

NARCIS (Netherlands)

Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

2012-01-01

Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199

RB1 mutations and second primary malignancies after hereditary retinoblastoma

NARCIS (Netherlands)

Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199

Treatment of Hereditary Hemorrhagic Telangiectasia-Related Epistaxis.

Science.gov (United States)

Sautter, Nathan B; Smith, Timothy L

2016-06-01

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an incidence of 1:5000. Recurrent, spontaneous epistaxis is the most common presenting symptom. Severity of epistaxis varies widely, from mild, self-limited nosebleeds to severe, life-threatening nasal hemorrhage. Treatment of HHT-related epistaxis presents a challenge to the otolaryngologist due to the recurrent, persistent nature of epistaxis often requiring multiple treatments. Treatment modalities range from conservative topical therapies to more aggressive surgical treatments. Copyright © 2016 Elsevier Inc. All rights reserved.

Genes for hereditary sensory and autonomic neuropathies : a genotype-phenotype correlation

NARCIS (Netherlands)

Rotthier, Annelies; Baets, Jonathan; De Vriendt, Els; Jacobs, An; Auer-Grumbach, Michaela; Levy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andres; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter; Timmerman, Vincent

2009-01-01

Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven

A role for MLH3 in hereditary nonpolyposis colorectal cancer

NARCIS (Netherlands)

Wu, Y; Berends, MJW; Sijmons, RH; Mensink, RGJ; Verlind, E; Kooi, KA; van der Sluis, T; Kempinga, C; van der Zee, AGJ; Hollema, H; Buys, CHCM; Kleibeuker, JH; Hofstra, RMW

2001-01-01

We investigated a possible role of the mismatch-repair gene MLH3 in hereditary nonpolyposis colorectal cancer by scanning for mutations in 39 HNPCC families and in 288 patients suspected of having HNPCC. We identified ten different germline MLH3 variants, one frameshift and nine missense mutations,

Visual Rehabilitation of Persons with Leber's Hereditary Optic Neuropathy.

Science.gov (United States)

Rudanko, S.-L.

1995-01-01

This article presents results of a noncontrolled clinical study of 20 persons with Leber's hereditary optic neuropathy who were treated from 1976 to 1990 at the Low Vision Centre of the Finnish Federation of the Visually Handicapped. The importance of early functional visual rehabilitation is emphasized, as is the use of low vision aids to help…

Hereditary angioedema by C1 inhibitor-deficit: Diagnostic and therapeutic challenges. Case report

Directory of Open Access Journals (Sweden)

Álvaro José Mayorga

2017-12-01

Conclusion: The delay diagnosis involves considerable risk in these patients; the importance of long-term prophylactic treatment is ratified in the use of androgens, being as an available option in developing countries.

A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes

DEFF Research Database (Denmark)

Joseph, Kusumam; Bains, Sonia; Tholanikunnel, Baby G

2015-01-01

. This was evident regardless whether we measured factor XIIa-C1-INH or kallikrein-C1-INH complexes, and the two assays were in close agreement. By contrast, testing the same samples utilizing the commercial method (complex ELISA, Quidel Corp.) revealed levels of C1-INH between 0 and 57% of normal (mean, 38%) and 42...

Misdiagnosis trends in patients with hereditary angioedema from the real-world clinical setting

DEFF Research Database (Denmark)

Zanichelli, Andrea; Longhurst, Hilary J; Maurer, Marcus

2016-01-01

. OBJECTIVE: To evaluate the history of misdiagnosis in patients participating in the Icatibant Outcome Survey (IOS). METHODS: The IOS is an observational study in which safety and effectiveness of icatibant have been evaluated since 2009. As part of the IOS, patients record any misdiagnoses received before...

Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test.

Science.gov (United States)

Nguyen, Kevin A; Syed, Jamil S; Espenschied, Carin R; LaDuca, Holly; Bhagat, Ansh M; Suarez-Sarmiento, Alfredo; O'Rourke, Timothy K; Brierley, Karina L; Hofstatter, Erin W; Shuch, Brian

2017-11-15

Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer. The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test. Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P kidney cancer. Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society. © 2017 American Cancer Society.

Atypical hereditary sensory and autonomic neuropathy type IV with neither mental retardation nor pain insensitivity.

Science.gov (United States)

Jung, Chae Lim; Ki, Chang-Seok; Kim, Byoung Joon; Lee, Jong-Hyuck; Sung, Ki-Sun; Kim, Jong-Won; Park, Youn-Soo

2013-12-01

Hereditary sensory and autonomic neuropathy type IV is an autosomal recessive disorder characterized by severe mental retardation and self-mutilation-related complications. Recently, we investigated a 16-year-old Korean boy with normal intelligence. He had preserved pain sensation but was suspected of having hereditary sensory and autonomic neuropathy type IV because of the recurrent bone fractures and painless joint destruction in the absence of any predisposing medical conditions. Genetic analysis of the NTRK1 gene revealed compound heterozygous mutations including c.851-33T>A and c.2303C>T (p.Pro768Leu) in the NTRK1 gene. The p.Pro768Leu mutation has been identified in 2 Japanese patients with a mild phenotype. Therefore, although it is rare, hereditary sensory and autonomic neuropathy type IV should be considered in patients with recurrent bone fractures and painless joint destruction who do not have any predisposing conditions even when they do not have typical clinical features such as mental retardation or pain insensitivity.

Utilization of the higher plants in a study on hereditary effect of low-dose irradiation

International Nuclear Information System (INIS)

Yamashita, Jun

1976-01-01

Some problems in a study of hereditary effect of low-dose irradiation, which used the higher plants (tradescantia, peas, etc.) as materials, were mentioned. Conditions to be used as materials were mentioned as follows: 1) the materials must have high radio-sensitivity, 2) the natural mutation of the materials must be low, 3) hereditary uniformity and stability of genes in the materials were important, and 4) in case of considering the materials as environmental radiation monitors, the observation period must be long and the duration from exposure to detection of mutation must be short. Tradescantia has most of these conditions, but the greatest fault is that the object of its observation is mutation of somatic cells, and hereditary study is impossible. Therefore, it is necessary to find out other materials in order to solve the problem whether there is a difference in relative frequency of chromosomal abnormalities, which occurrs in germinal cells and is transmitted to posterity, between low and high doses or not. (Serizawa, K.)

Clinical and electromyographic criteria for the diagnosis of hereditary myotonic syndromes

Directory of Open Access Journals (Sweden)

V. P. Fedotov

2012-01-01

Full Text Available Hereditary myotonic syndromes (HMS are a group of genetically heterogeneous diseases of the chlorine and sodium ion channels (channelopathies with evident clinical polymorphism and high prevalence in the population. The differential diagnosis of early‑stage NMS poses a challenge to clinicians to this day. The investigation has attempted to elaborate informative differentiating criteria on the basis of a clinical and electromyographic study of 2 groups of patients with hereditary Thomsen or Becker myotonia (n = 45 and myotonic dystrophy type 1 (n = 39 verified by DNA analysis of the CLCN1 and DMPK genes. Along with the clinical symptoms, there may be the value of M‑response amplitude decrement in rhythmic stimulation of the n. ulnaris and the duration of myotonic discharges at pin electromyography of the m. tibialis anterior.

Hereditary motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough.

Science.gov (United States)

Miura, Shiroh; Shibata, Hiroki; Kida, Hiroshi; Noda, Kazuhito; Tomiyasu, Katsuro; Yamamoto, Ken; Iwaki, Akiko; Ayabe, Mitsuyoshi; Aizawa, Hisamichi; Taniwaki, Takayuki; Fukumaki, Yasuyuki

2008-10-15

We studied a four-generation pedigree of a Japanese family with hereditary neuropathy to elucidate the genetic basis of this disease. Twelve members of the family were enrolled in this study. The clinical features were neurogenic muscle weakness with proximal dominancy in the lower extremities, sensory involvement, areflexia, fine postural tremors, painful muscle cramps, elevated creatine kinase levels, recurrent paroxysmal dry cough, and neurogenic bladder. We performed a genome-wide search using genetic loci spaced at about 13 Mb intervals. Although nine chromosomes (1, 3, 4, 5, 6, 10, 17, 19, and 22) had at least one region in which the logarithm of odds (LOD) score was over 1.0, no loci fulfilled the criteria for significant evidence of linkage. Moreover, we analyzed an extra 14 markers on 3p12-q13 (the locus of hereditary motor and sensory neuropathy, proximal dominant form) and an extra five markers on 3p22-p24 (the locus of hereditary sensory neuropathy with chronic cough) and observed LOD scores of hereditary motor and sensory neuropathy with autosomal dominant inheritance.

International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency

DEFF Research Database (Denmark)

Caballero, Teresa; Farkas, Henriette; Bouillet, Laurence

2012-01-01

devices, and progestins can be used. Pregnancy: Attenuated androgens are contraindicated and should be discontinued before attempting conception. Plasma-derived human C1 inhibitor concentrate (pdhC1INH) is preferred for acute treatment, short-term prophylaxis, or long-term prophylaxis. Tranexamic acid...

Evaluation of an online family history tool for identifying hereditary and familial colorectal cancer.

Science.gov (United States)

Kallenberg, F G J; Aalfs, C M; The, F O; Wientjes, C A; Depla, A C; Mundt, M W; Bossuyt, P M M; Dekker, E

2017-09-21

Identifying a hereditary colorectal cancer (CRC) syndrome or familial CRC (FCC) in a CRC patient may enable the patient and relatives to enroll in surveillance protocols. As these individuals are insufficiently recognized, we evaluated an online family history tool, consisting of a patient-administered family history questionnaire and an automated genetic referral recommendation, to facilitate the identification of patients with hereditary CRC or FCC. Between 2015 and 2016, all newly diagnosed CRC patients in five Dutch outpatient clinics, were included in a trial with a stepped-wedge design, when first visiting the clinic. Each hospital continued standard procedures for identifying patients at risk (control strategy) and then, after a predetermined period, switched to offering the family history tool to included patients (intervention strategy). After considering the tool-based recommendation, the health care provider could decide on and arrange the referral. Primary outcome was the relative number of CRC patients who received screening or surveillance recommendations for themselves or relatives because of hereditary CRC or FCC, provided by genetic counseling. The intervention effect was evaluated using a logit-linear model. With the tool, 46/489 (9.4%) patients received a screening or surveillance recommendation, compared to 35/292 (12.0%) in the control group. In the intention-to-treat-analysis, accounting for time trends and hospital effects, this difference was not statistically significant (p = 0.58). A family history tool does not necessarily assist in increasing the number of CRC patients and relatives enrolled in screening or surveillance recommendations for hereditary CRC or FCC. Other interventions should be considered.

Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in metabolism and epigenome regulation.

Science.gov (United States)

Hasumi, Hisashi; Yao, Masahiro

2018-03-01

Although hereditary kidney cancer syndrome accounts for approximately five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, USA and the first kidney cancer-associated gene, VHL, was identified through kindred analysis of von Hippel-Lindau (VHL) syndrome in 1993. Subsequent molecular studies on VHL function have elucidated that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia-inducible factor (HIF), which provided the basis for the development of tyrosine kinase inhibitors targeting the HIF-VEGF/PDGF pathway. Recent whole-exome sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations in chromatin remodeling genes and the later study has revealed that several chromatin remodeling genes are altered in kidney cancer kindred at the germline level. To date, more than 10 hereditary kidney cancer syndromes together with each responsible gene have been characterized and most of the causative genes for these genetic disorders are associated with either metabolism or epigenome regulation. In this review article, we describe the molecular mechanisms of how an alteration of each kidney cancer-associated gene leads to renal tumorigenesis as well as denote therapeutic targets elicited by studies on hereditary kidney cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.

Science.gov (United States)

Robinson, Bruce G; Paz-Ares, Luis; Krebs, Annetta; Vasselli, James; Haddad, Robert

2010-06-01

Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC. Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors. The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies. Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.

A mountain among molehills: removing an impinging large femoral neck osteochondroma in a man with hereditary multiple exostoses.

LENUS (Irish Health Repository)

Fitzgerald, Conall W R

2014-01-01

A 31-year-old man with a history of hereditary multiple exostoses (HME) presented with persistent right groin pain and reduced hip range of movement. Examination demonstrated a positive FADIR (flexion, adduction and internal rotation) test suggesting femoroacetabular impingement (FAI). Investigations showed multiple sessile osteochondromata of the right femur with a dominant anterolateral femoral neck osteochondroma causing flexion block. The patient underwent an uncomplicated proximal femoral exostectomy. Six-week postoperative pain, range of movement and daily activity had greatly improved. This case highlights that even in the setting of multiple osteochondromata, excellent impingement relief can be achieved following selective proximal femoral exostectomy.

Hereditary melanoma and predictive genetic testing: why not?

Science.gov (United States)

Riedijk, S R; de Snoo, F A; van Dijk, S; Bergman, W; van Haeringen, A; Silberg, S; van Elderen, T M T; Tibben, A

2005-09-01

Since p16-Leiden presymptomatic testing for hereditary melanoma has become available in the Netherlands, the benefits and risks of offering such testing are evaluated. The current paper investigated why the non-participants were reluctant to participate in genetic testing. Sixty six eligible individuals, who were knowledgeable about the test but had not participated in genetic testing by January 2003, completed a self-report questionnaire assessing motivation, anxiety, family dynamics, risk knowledge and causal attributions. Non-participants reported anxiety levels below clinical significance. A principal components analysis on reasons for non-participation distinguished two underlying motives: emotional and rational motivation. Rational motivation for non-participation was associated with more accurate risk knowledge, the inclination to preselect mutation carriers within the family and lower scores on anxiety. Emotional motivation for non-participation was associated with disease misperceptions, hesitation to communicate unfavourable test results within the family and higher scores on anxiety. Rational and emotional motivation for non-participation in the genetic test for hereditary melanoma was found. Emotionally motivated individuals may be reluctant to disseminate genetic risk information. Rationally motivated individuals were better informed than emotionally motivated individuals. It is suggested that a leaflet is added to the invitation letter to enhance informed decision-making about genetic testing.

Macroorchidism in FMR1 knockout mice is caused by increased Sertoli cell proliferation during testicular development

NARCIS (Netherlands)

K.E. Slegtenhorst-Eegdeman; D.G. de Rooij; M. Verhoef-Post (Miriam); H.J.G. van de Kant (Henk); C.E. Bakker (Cathy); B.A. Oostra (Ben); J.A. Grootegoed (Anton); A.P.N. Themmen (Axel)

1998-01-01

textabstractThe fragile X syndrome is the most frequent hereditary form of mental retardation. This X-linked disorder is, in most cases, caused by an unstable and expanding trinucleotide CGG repeat located in the 5'-untranslated region of the gene involved, the fragile

Platelet fibrinogen binding in Basset Hound Hereditary Thrombopathy

International Nuclear Information System (INIS)

Patterson, W.; Estry, D.; Schwartz, K.; Bell, T.

1986-01-01

Platelets from dogs with Basset Hound Hereditary Thrombopathy (BHT) display a thrombasthenia-like aggregation defect but have been shown to have normal amounts of platelet membrane glycoproteins IIb and IIIa (GP IIb-IIIa). In order to investigate the possibility of a functionally abnormal GPIIb-IIIa complex, which might be unable to bind fibrinogen after stimulation, fibrinogen binding in BHT was evaluated. Two canine fibrinogen preparations were used, one from BHT dogs and one from normal control dogs, as well as a human fibrinogen preparation. Platelets from BHT and normal dogs were activated with 1 x 10 -5 M ADP in the presence of 125 I-labeled fibrinogen and the surface bound radioactivity quantitated. For all fibrinogen preparations, the amount of fibrinogen bound by BHT platelets was not significantly different than that bound by normal dog platelets. BHT platelets bound 23,972 +/- 3612 and normal dog platelets bound 23,033 +/- 3971 molecules of fibrinogen per platelet. The BHT platelet aggregation defect does not seem to be caused by a functionally abnormal GP IIb-IIIa complex, since BHT platelets bind normal amounts of fibrinogen. The results suggest that fibrinogen binding is not sufficient for platelet aggregation, and other factors, perhaps receptor mobility and membrane phospholipid content should be investigated in BHT

HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (LYNCH SYNDROME PADA WANITA UMUR 16 TAHUN

Directory of Open Access Journals (Sweden)

Asril Zahari

2011-09-01

Full Text Available AbstrakKanker kolorektal menduduki peringkat ketiga jenis kanker yang paling sering terjadi di dunia. Sekitar 3% kasus kanker kolorektal merupakan jenis hereditary non polyposis colorectal cancer (HNPCC/Lynch syndrome, yang sering muncul pada usia muda. Dilaporkan satu kasus di rumah sakit Dr. M. Djamil Padang, wanita berumur 16 tahun dengan keluhan nyeri perut kanan bawah. Didapatkan riwayat penyakit serupa pada kakek, bibi pasien dan enam anggota keluarga yang lain. Pada pemeriksaan fisik abdomen teraba massa dengan konsistensi keras dan terfiksir. Pada kolonoskopi dan biopsi ditemukan tumor jenis adenocarcinoma colon moderatly differentiated di fleksura hepatika dan polip di kolon sigmoid. Berdasarkan kriteria Amsterdam pasien didiagnosa Lynch syndrome. Pada Pasien dilakukan subtotal kolektomi, anastomose ileorectal dan kemoterapi ajuvan. Identifikasi genetik sedang dikerjakan untuk melihat adanya kelainan genetik pada pasien. Pasien melakukan skrining berkala untuk mencegah kanker HNPCC jenis yang lain.Kata kunci : Hereditary non polyposis colorectal cancer, Lynch syndrome, Microsatellite instability, skrining.AbstractCarcinoma colorectal is the third most common type of cancer that occurs in the world. About 2% -3% of cases of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC/Lynch syndrome, which often appear at a young age. Amsterdam and Bethesda criteria have been used to identify patients with Lynch syndrome.one case was reported at the Dr. M. Djamil Padang hospital, a 16-year-old girl with right lower abdominal pain. Obtained a history of similar disease in grandparents, aunts and six other family members. On physical examination found palpable fixed abdominal mass with hard consistency in the lower right abdomen. At colonoscopy and biopsy found a moderatly differentiated adenocarcinoma colon type at the hepatic flexure and the sigmoid colon polyp. Based on the Amsterdam criteria, patients diagnosed with HNPCC

Frequency of breast cancer with hereditary risk features in Spain: Analysis from GEICAM "El Álamo III" retrospective study.

Science.gov (United States)

Márquez-Rodas, Iván; Pollán, Marina; Escudero, María José; Ruiz, Amparo; Martín, Miguel; Santaballa, Ana; Martínez Del Prado, Purificación; Batista, Norberto; Andrés, Raquel; Antón, Antonio; Llombart, Antonio; Fernandez Aramburu, Antonio; Adrover, Encarnación; González, Sonia; Seguí, Miguel Angel; Calvo, Lourdes; Lizón, José; Rodríguez Lescure, Álvaro; Ramón Y Cajal, Teresa; Llort, Gemma; Jara, Carlos; Carrasco, Eva; López-Tarruella, Sara

2017-01-01

To determine the frequency of breast cancer (BC) patients with hereditary risk features in a wide retrospective cohort of patients in Spain. a retrospective analysis was conducted from 10,638 BC patients diagnosed between 1998 and 2001 in the GEICAM registry "El Álamo III", dividing them into four groups according to modified ESMO and SEOM hereditary cancer risk criteria: Sporadic breast cancer group (R0); Individual risk group (IR); Familial risk group (FR); Individual and familial risk group (IFR) with both individual and familial risk criteria. 7,641 patients were evaluable. Of them, 2,252 patients (29.5%) had at least one hereditary risk criteria, being subclassified in: FR 1.105 (14.5%), IR 970 (12.7%), IFR 177 (2.3%). There was a higher frequency of newly diagnosed metastatic patients in the IR group (5.1% vs 3.2%, p = 0.02). In contrast, in RO were lower proportion of big tumors (> T2) (43.8% vs 47.4%, p = 0.023), nodal involvement (43.4% vs 48.1%, p = 0.004) and lower histological grades (20.9% G3 for the R0 vs 29.8%) when compared to patients with any risk criteria. Almost three out of ten BC patients have at least one hereditary risk cancer feature that would warrant further genetic counseling. Patients with hereditary cancer risk seems to be diagnosed with worse prognosis factors.

The influence of coping styles and perceived control on emotional distress in persons at risk for a hereditary heart disease

NARCIS (Netherlands)

Hoedemaekers, Ehy; Jaspers, Jan P. C.; Van Tintelen, J. Peter

2007-01-01

This prospective study investigates the influence of two coping styles (monitoring and blunting) and perceived control (health loci-is of control and mastery) on emotional distress in persons at risk of a hereditary cardiac disease. Emotional distress in people at risk for a hereditary cardiac

The Prevention of Hereditary Breast and Ovarian Cancer: A Personal View

Directory of Open Access Journals (Sweden)

Narod Steven

2004-02-01

Full Text Available Abstract Options for the prevention of hereditary breast and ovarian cancer include screening, preventive surgery and chemoprevention. Screening studies with magnetic resonance imaging of the breast are promising but the technology is not widespread and MRI is unlikely to be available as a screening tool in the near future. Prophylactic oophorectomy and mastectomy are effective preventive measures and are gaining in acceptance by patients and physicians. Preventive mastectomy is effective against both primary and contralateral breast cancer. Oophorectomy prevents ovarian cancer, and if done prior to menopause, will prevent breast cancer as well. Tamoxifen has been shown to prevent contralateral breast cancers in BRCA1 and BRCA2 carriers but is not widely accepted as a means of primary prevention. Oral contraceptives and tubal ligation will reduce the risk of hereditary ovarian cancer and should be considered in women who wish to retain ovarian function.

Age-dependent cognitive dysfunction in untreated hereditary transthyretin amyloidosis.

Science.gov (United States)

Martins da Silva, Ana; Cavaco, Sara; Fernandes, Joana; Samões, Raquel; Alves, Cristina; Cardoso, Márcio; Kelly, Jeffery W; Monteiro, Cecília; Coelho, Teresa

2018-02-01

Central nervous system (CNS) involvement in hereditary transthyretin (TTR) amyloidosis has been described in patients whose disease course was modified by liver transplant. However, cognitive dysfunction has yet to be investigated in those patients. Moreover, CNS involvement in untreated patients or asymptomatic mutation carriers remains to be studied. A series of 340 carriers of the TTRVal30Met mutation (180 symptomatic and 160 asymptomatic) underwent a neuropsychological assessment, which included the Dementia Rating Scale-2 (DRS-2), auditory verbal learning test, semantic fluency, phonemic fluency, and trail making test. Cognitive deficits were identified at the individual level, after adjusting the neuropsychological test scores for demographic characteristics (sex, age, and education), based on large national normative data. The presence of cognitive dysfunction was determined by deficit in DRS-2 and/or multiple cognitive domains. Participants were also screened for depression based on a self-report questionnaire. The frequency of cognitive dysfunction was higher (p = 0.003) in symptomatic (9%) than in asymptomatic (2%) carriers. Among older carriers (≥ 50 years), the frequency of cognitive dysfunction was higher (p hereditary TTR amyloidosis patients with peripheral polyneuropathy, even in the early stages of the disease.

Diagnosis of Lynch Syndrome: Genetic Testing Identifies a Potentially Deadly Hereditary Disease

Science.gov (United States)

... of Lynch Syndrome Follow us A Diagnosis of Lynch Syndrome Genetic testing identifies a potentially deadly hereditary disease ... helped Jack learn what was wrong. Jack had Lynch Syndrome—an inherited disorder. Lynch Syndrome increases the risk ...

ACOUSTIC WAVES EMISSION IN THE TWO-COMPONENT HEREDITARY-ELASTIC MEDIUM

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V. S. Polenov

2014-01-01

Full Text Available Summary. On the dynamics of two-component media a number of papers, which address the elastic waves in a homogeneous, unbounded fluid-saturated porous medium. In other studies address issues of dissipative processes in harmonic deformation hereditary elastic medium. In the article the dissipative processes of the viscoelastic porous medium, which hereditary properties are described by the core relaxation fractional exponential function U.N. Rabotnova integro-differential Boltzmann-Volterr ratio, harmonic deformation by the straining saturated incompressible liquid are investigated. Speed of wave propagation, absorption coefficient, mechanical loss tangent, logarithmic decrement, depending on fractional parameter γ, determining formulas received. The frequency logarithm and temperature graph dependences with the goal fractional parameter are constructed. Shows the dependences velocity and attenuation coefficient of the tangent of the phase angle of the logarithm of the temperature, and the dependence of the attenuation coefficient of the logarithm of the frequency. Dependencies the speed and the tangent of the phase angle of the frequency identical function of the logarithm of temperature.

De-novo mutation in hereditary motor and sensory neuropathy type I

NARCIS (Netherlands)

Hoogendijk, J. E.; Hensels, G. W.; Gabreëls-Festen, A. A.; Gabreëls, F. J.; Janssen, E. A.; de Jonghe, P.; Martin, J. J.; van Broeckhoven, C.; Valentijn, L. J.; Baas, F.

1992-01-01

Isolated cases of hereditary motor and sensory neuropathy type I (HMSN I, Charcot-Marie-Tooth disease type 1) have been thought to be most frequently autosomal recessive. We have found that a recently discovered duplication in chromosome 17, responsible for most cases of autosomal dominant HMSN I,

Genes for Hereditary Sensory and Autonomic Neuropathies: A Genotype-Phenotype Correlation

Science.gov (United States)

Rotthier, Annelies; Baets, Jonathan; De Vriendt, Els; Jacobs, An; Auer-Grumbach, Michaela; Levy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andres; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter; Timmerman, Vincent

2009-01-01

Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven genes: two genes for autosomal dominant ("SPTLC1"…

A mouse model of hereditary coproporphyria identified in an ENU mutagenesis screen

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Ashlee J. Conway

2017-08-01

Full Text Available A genome-wide ethyl-N-nitrosourea (ENU mutagenesis screen in mice was performed to identify novel regulators of erythropoiesis. Here, we describe a mouse line, RBC16, which harbours a dominantly inherited mutation in the Cpox gene, responsible for production of the haem biosynthesis enzyme, coproporphyrinogen III oxidase (CPOX. A premature stop codon in place of a tryptophan at amino acid 373 results in reduced mRNA expression and diminished protein levels, yielding a microcytic red blood cell phenotype in heterozygous mice. Urinary and faecal porphyrins in female RBC16 heterozygotes were significantly elevated compared with that of wild-type littermates, particularly coproporphyrinogen III, whereas males were biochemically normal. Attempts to induce acute porphyric crises were made using fasting and phenobarbital treatment on females. While fasting had no biochemical effect on RBC16 mice, phenobarbital caused significant elevation of faecal coproporphyrinogen III in heterozygous mice. This is the first known investigation of a mutagenesis mouse model with genetic and biochemical parallels to hereditary coproporphyria.

A Case of Apparent Contact Dermatitis Caused by Toxocara Infection

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Rosanna Qualizza

2014-01-01

Full Text Available Infection from Toxocara species may give rise to a large array of clinical symptoms, including apparent manifestations of allergy such as asthma, urticaria/angioedema, and dermatitis. We report a case, thus far not described, of contact dermatitis attributed to nickel allergy but caused by Toxocara infection. The patient was a 53-year-old woman presenting from 10 years a dermatitis affecting head, neck, and thorax. Patch tests initially performed gave a positive result to nickel, but avoidance of contact with nickel did not result in recovery. The patient referred to our Allergy Service in 2010 because of dermatitis to feet. Patch testing confirmed the positive result for nickel, but expanding the investigation a positive result for IgG antibodies to Toxocara was detected by Western blotting and ELISA. Treatment with mebendazole achieved immediate efficacy on feet dermatitis. Then, two courses of treatment with albendazole resulted in complete regression of dermatitis accompanied by development of negative ELISA and Western blotting for Toxocara antibodies. This report adds another misleading presentation of Toxocara infection as apparent contact dermatitis caused by nickel and suggests bearing in mind, in cases of contact dermatitis not responding to avoidance of the responsible hapten and to medical treatment, the possible causative role of Toxocara.

Hereditary nonpolyposis colorectal cancer: not just a barium enema{exclamation_point} Radiographic manifestations and screening tools

Energy Technology Data Exchange (ETDEWEB)

Foster, L.; Jeon, P. [Health Sciences Center, Diagnostic Imaging, St. John' s, Newfoundland (Canada)]. E-mail: u43dlb@mun.ca; Green, J. [Health Sciences Center, Discipline of Genetics, Faculty of Medicine, St. John' s, Newfoundland (Canada)

2007-10-15

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant trait characterized by presentation of colorectal cancer (CRC) at an early age and by an increased risk of other primary malignancies, including those of the endometrium. ovaries, stomach, small bowel, upper biliary tract, skin, and brain, as well as by transitional cell carcinoma (TCC) that especially involves the renal pelvis and ureter. Because specific genetic mutations causing HNPCC have been recently discovered, genetic screening options have been developed for some families. Subsequently, radiology has an increasing role in surveillance for and management of these HNPCC-associated tumours. Although colonoscopy is the mainstay of a screening regimen for colon cancer, the barium enema has been a standard radiologic investigation. Further, computed tomography (CT) colonography (now practised in various centres) will, with further refinement, prove to be of increasing value. Ultrasonography is a standard investigation for endometrial and ovarian cancer, with CT and magnetic resonance (MR) imaging often playing a central role. As for TCC, intravenous urography (IVU) had been a standard investigation tool. However, with continued evolution of multidetector row CT with postprocessing manipulation (CT urography [CTU]), the role of IVU is diminishing in most centres. Newfoundland has a high prevalence of HNPCC exhibiting a broad range of manifestations. In this article, radiologic images of various tumours from individuals with HNPCC demonstrate a radiologic spectrum of this fascinating hereditary disease. Screening implications and specific screening methods are reviewed. (author)

Hereditary Breast Cancer: Mutations Within BRCA1 and BRCA2 with Phenotypic Responses

National Research Council Canada - National Science Library

Lynch, Henry T

2000-01-01

To date we have seventy-three Hereditary Breast/Ovarian Cancer families with identified BRCA1 or BRCA2 genetic mutations, wherein 24 additional cases of slides and tissue blocks have been retrieved...

Parent Beliefs about the Causes of Learning and Developmental Problems among Children with Autism Spectrum Disorder: Results from a National Survey

Science.gov (United States)

Zuckerman, Katharine E.; Lindly, Olivia J.; Sinche, Brianna

2016-01-01

This study aimed to assess variation in parent beliefs about causes of learning and developmental problems in U.S. children with autism spectrum disorder, using data from a nationally representative survey. Results showed that beliefs about a genetic/hereditary cause of learning/developmental problems were most common, but nearly as many parents…

Urinary tract cancer and hereditary nonpolyposis colorectal cancer : Risks and screening options

NARCIS (Netherlands)

Sijmons, RH; Kiemeney, LALM; Witjes, JA; Vasen, HFA

Purpose: We investigate the risk of the different types of urinary tract cancer in hereditary nonpolyposis colorectal cancer families and review screening options. Materials and Methods: We retrospectively calculated the relative and cumulative risks of developing urinary tract cancer by comparing

Family history record and hereditary cancer risk perception according to National Cancer Institute criteria in a Spanish medical oncology service: a retrospective study.

Science.gov (United States)

Márquez-Rodas, Iván; López-Trabada, Daniel; Rupérez Blanco, Ana Belén; Custodio Cabello, Sara; Peligros Gómez, María Isabel; Orera Clemente, María; Calvo, Felipe A; Martín, Miguel

2012-01-01

Identification of patients at risk of hereditary cancer is an essential component of oncology practice, since it enables clinicians to offer early detection and prevention programs. However, the large number of hereditary syndromes makes it difficult to take them all into account in daily practice. Consequently, the National Cancer Institute (NCI) has suggested a series of criteria to guide initial suspicion. It was the aim of this study to assess the perception of the risk of hereditary cancer according to the NCI criteria in our medical oncology service. We retrospectively analyzed the recordings of the family history in new cancer patients seen in our medical oncology service from January to November 2009, only 1 year before the implementation of our multidisciplinary hereditary cancer program. The family history was recorded in only 175/621 (28%) patients. A total of 119 (19%) patients met 1 or more NCI criteria (1 criterion, n = 91; 2 criteria, n = 23; 3 criteria, n = 4; and 4 criteria, n = 1), and only 14 (11.4%) patients were referred to genetic counseling. This study shows that few clinicians record the family history. The perception of the risk of hereditary cancer is low according to the NCI criteria in our medical oncology service. These findings can be explained by the lack of a multidisciplinary hereditary cancer program when the study was performed. Copyright © 2012 S. Karger AG, Basel.

Ethical dilemmas in genetic testing: examples from the Cuban program for predictive diagnosis of hereditary ataxias.

Science.gov (United States)

Mariño, Tania Cruz; Armiñán, Rubén Reynaldo; Cedeño, Humberto Jorge; Mesa, José Miguel Laffita; Zaldivar, Yanetza González; Rodríguez, Raúl Aguilera; Santos, Miguel Velázquez; Mederos, Luis Enrique Almaguer; Herrera, Milena Paneque; Pérez, Luis Velázquez

2011-06-01

Predictive testing protocols are intended to help patients affected with hereditary conditions understand their condition and make informed reproductive choices. However, predictive protocols may expose clinicians and patients to ethical dilemmas that interfere with genetic counseling and the decision making process. This paper describes ethical dilemmas in a series of five cases involving predictive testing for hereditary ataxias in Cuba. The examples herein present evidence of the deeply controversial situations faced by both individuals at risk and professionals in charge of these predictive studies, suggesting a need for expanded guidelines to address such complexities.

Skin deposits in hereditary cystatin C amyloidosis

DEFF Research Database (Denmark)

Benedikz, Eirikur; Blöndal, H; Gudmundsson, G

1990-01-01

Clinically normal skin from 47 individuals aged 9-70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic...... individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17-46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker...

Hereditary sensory and autosomal peripheral neuropathy-type IV: case series and review of literature.

Science.gov (United States)

Ashwin, D P; Chandan, G D; Jasleen, Handa Kaur; Rajkumar, G C; Rudresh, K B; Prashanth, R

2015-06-01

Hereditary sensory and autonomic neuropathy (HSAN) IV is a rare autosomal recessive disorder which is characterized by a decrease in the number of myelinated and non-myelinated nerve fibers of peripheral nerves which causes diminished or absent pain sensation leading to increase in self-mutilative habits. A retrospective study of eight cases ranging from age group of 4 to 17 years for oral and digital signs and symptoms is presented. All the patients showed congenital insensitivity to pain and anhidrosis. Oral self-mutilations, such as autoextraction of teeth and severe bite injuries (with resultant scarring) of the finger tips and oral soft tissues (tongue, lip, and buccal mucosa) were found in most patients. Our study suggests that early diagnosis and specific treatment plan are important for prevention of characteristic of the oral as well as digital trauma associated with this disorder.

[Hereditary colorectal cancer : An update on genetics and entities in terms of differential diagnosis].

Science.gov (United States)

Rau, T T; Dawson, H; Hartmann, A; Rüschoff, J

2017-05-01

The pathologist can contribute to recognizing hereditary causes of colorectal cancer via morphology. By identifying so-called index patients, it is possible to take preventive measures in affected families. The precise definition of the clinical presentation and the histopathological phenotype help to narrow the spectrum of expected genetic alterations. Novelties within Lynch syndrome include the recognition of EPCAM as a fifth gene locus, as well as the newly defined Lynch-like syndrome with evidence of somatic mismatch repair (MMR) mutations. With regard to polyposis-associated syndromes, the spectrum of polyps, whether serrated, hamartomatous or classic adenoma, is of crucial importance. The resulting differential diagnosis includes (attenuated) familial adenomatous polyposis ([a]FAP), MUTYH-associated polyposis (MAP), polymerase proofreading-associated polyposis (PPAP), phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS), Peutz-Jeghers syndrome and juvenile polyposis, each with a specific genetic background.

The brain in hereditary hemorrhagic telangiectasia with pulmonary AVM: The clinical importance of paradoxical embolism

International Nuclear Information System (INIS)

Kim, W.S.; Kinnison, M.L.; Charnas, L.; Rosenbaum, A.E.; White, R.I. Jr.

1986-01-01

Despite the literature's emphasis on the presence of intracerebral vascular malformations in hereditary hemorrhagic telangiectasia (HHT), few cases have been documented. The authors prospectively evaluated brain CT scans in 29 consecutive patients with pulmonary arteriovenous malformations (AVMs) and known HHT. Fifty-five percent of the CT scans revealed the signs of embolic phenomena: infarctions (n=11) and intracerebral abscesses (n=5). In only one patient was a small enhancing vascular lesion seen. They conclude that embolic phenomena rather than vascular malformations cause the majority of abnormal CT findings in patients with HHT and pulmonary AVMs. Infarctions and intracerebral abscesses probably result from paradoxical embolization through the AVMs in the lungs. The therapeutic implications seem clear, since 55% of these patients are potentially treatable by balloon occlusion of the pulmonary AVMs

[Hereditary motor and sensory neuropathy type 4A].

Science.gov (United States)

Shagina, O A; Dadali, E L; Fedotov, V P; Tiburkova, T B; Poliakov, A V

2010-01-01

The first in the Russian Federation clinical cases of patients with autosomal-recessive type of hereditary motor and sensory neuropathy, type 4A, (HMSN 4A) are presented. In all cases, the diagnosis has been verified using molecular-genetic methods (DNA diagnostics). An analysis of features of clinical manifestations was performed in patients, aged from 5 to 34 years, with different disease duration (from 3-to 29 years). Criteria of selection of patients for DNA diagnostics for searching mutations in the GDAP1 gene are specified.

Serial CT Findings of Resolving Extramedullary Hematopoiesis as Unilateral Posterior Mediastinal Mass after Splenectomy in Hereditary Spherocytosis: A Case Report

International Nuclear Information System (INIS)

Nam, Mi Yeon; Lee, Ju Won; Kim, Yeo Ju; Kim, Youn Jeong; Kang, Young Hye; Lee, Kyung Hee

2012-01-01

Intrathoracic extramedullary hematopoiesis (EMH) is a rare condition of the hereditary spherocytosis. EMH usually regresses or disappears after treatment; such as splenectomy in the case of spherocytosis. We report a case of hereditary spherocytosis. It is presented with an unilateral paravertebral posterior mediastinal mass. After splenectomy, it revealed shrinkage and fatty replacement on serial CT scans.

Serial CT Findings of Resolving Extramedullary Hematopoiesis as Unilateral Posterior Mediastinal Mass after Splenectomy in Hereditary Spherocytosis: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Nam, Mi Yeon; Lee, Ju Won; Kim, Yeo Ju; Kim, Youn Jeong; Kang, Young Hye; Lee, Kyung Hee [Dept. of Radiology, Inha University Hospital, Incheon (Korea, Republic of)

2012-03-15

Intrathoracic extramedullary hematopoiesis (EMH) is a rare condition of the hereditary spherocytosis. EMH usually regresses or disappears after treatment; such as splenectomy in the case of spherocytosis. We report a case of hereditary spherocytosis. It is presented with an unilateral paravertebral posterior mediastinal mass. After splenectomy, it revealed shrinkage and fatty replacement on serial CT scans.

Analysis of Hereditary Elliptocytosis with Decreased Binding of Eosin-5-maleimide to Red Blood Cells

Directory of Open Access Journals (Sweden)

Shin-ichiro Suemori

2015-01-01

Full Text Available Flow cytometric test for analyzing the eosin-5-maleimide (EMA binding to red blood cells has been believed to be a specific method for diagnosing hereditary spherocytosis (HS. However, it has been reported that diseases other than HS, such as hereditary pyropoikilocytosis (HPP and Southeast Asian ovalocytosis (SAO, which are forms in the category of hereditary elliptocytosis (HE, show decreased EMA binding to red blood cells. We analyzed EMA binding to red blood cells in 101 healthy control subjects and 42 HS patients and obtained a mean channel fluorescence (MCF cut-off value of 36.4 (sensitivity 0.97, specificity 0.95. Using this method, we also analyzed 12 HE patients. Among them, four HE patients showed the MCF at or below the cut-off value. It indicates that some HE patients have decreased EMA binding to red blood cells. Two of these four HE patients were classified as common HE, and two were spherocytic HE with reduced spectrin. This study demonstrates that, in addition to patients with HPP or SAO, some HE patients have decreased EMA binding to red blood cells.

Genetics Home Reference: hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis

Science.gov (United States)

... Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis Printable PDF Open All Close All Enable Javascript ... Fibrosing Poikiloderma with Tendon Contractures, Myopathy, and Pulmonary ... Lung, and Blood Institute (NHLBI): Pulmonary Function Tests National ...

Hereditary hypohidrotic ectodermal dysplasia: report of a rare case.

Science.gov (United States)

Paramkusam, Geetha; Meduri, Venkateswarlu; Nadendla, Lakshmi Kavitha; Shetty, Namratha

2013-09-01

Hereditary Hypohidrotic Ectodermal Dysplasia (HHED), an X-linked, recessive, Mendelian character, is seen usually in males and it is inherited through female carriers. It is characterised by congenital dysplasia of one or more ectodermal structures and it is manifested by hypohidrosis, hypotrichosis and hypodontia. It results from abnormal morphogenesis of cutaneous and oral embryonic ectoderm. Here, we are presenting a rare case of HHED in a 19 year female with classic features of this condition.