De novo arteriovenous malformation in a patient with hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant systemic disorder characterized by the enlargement of capillaries, recurrent nosebleeds, and multiple arteriovenous malformations (AVMs). Although cerebral AVMs are traditionally considered to be congenital lesions, some reports have described de novo AVMs, which suggests that the authors believed them to be dynamic conditions. In this article, the authors describe the case of a 5-year-old boy with HHT in whom a de novo cerebral AVM was detected after a negative MRI result at 5 months. To the authors’ knowledge, this is the first report of a de novo AVM in a patient with HHT. In patients with a family history of HHT, de novo AVMs are possible, even when no lesions are detected at the first screening. Therefore, regular screenings need to be performed, and the family should be informed that AVMs could still develop despite normal MRI results.

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Hereditary Hemorrhagic Telangiectasia: A Genetic Disorder with Oral Manifestations

International Journal of Experimental Dental Science ◽

10.5005/jp-journals-10029-1069 ◽

2014 ◽

Vol 3 (1) ◽

pp. 49-52

Author(s):

Apollonia Desiate ◽

Stefania Cantore ◽

Andrea Ballini

Keyword(s):

Family History ◽

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

Autosomal Dominant ◽

Genetic Disorder ◽

Oral Manifestations ◽

Systemic Diseases ◽

Recurrent Epistaxis ◽

History Of ◽

Broad Understanding

ABSTRACT The case of a 74-year-old man who was diagnosed as having hereditary hemorrhagic telangiectasia (HHT), with telangiectasies localized in oral district is presented. This condition is an autosomal dominant mucocutaneous and visceral fibrovascular dysplasia in which telangiectasia, arteriovenous malformations and aneurysms may be widely distributed throughout the cardiovascular system. It is usually recognized as a ‘triad’ of telangiectasia, recurrent epistaxis and a family history of the disorder. The nature of the practice of dentistry necessitates a broad understanding of the systemic diseases reflected in the oral cavity. Hereditary hemorrhagic telangiectasia is one such disease. How to cite this article Ballini A, Cantore S, Desiate A. Hereditary Hemorrhagic Telangiectasia: A Genetic Disorder with Oral Manifestations. Int J Experiment Dent Sci 2014; 3(1): 49-52.

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Genetic testing for hereditary hemorrhagic telangiectasia

The EuroBiotech Journal ◽

10.2478/ebtj-2018-0031 ◽

2018 ◽

Vol 2 (s1) ◽

pp. 32-34

Author(s):

Yeltay Rakhmanov ◽

Paolo Enrico Maltese ◽

Stefano Paolacci ◽

Carla Marinelli ◽

Raul Ettore Mattassi ◽

...

Keyword(s):

Risk Assessment ◽

Clinical Trials ◽

Differential Diagnosis ◽

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

Autosomal Dominant ◽

De Novo ◽

Incomplete Penetrance ◽

Gene Test ◽

Vascular Dysplasia

Abstract Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by telangiectases and arteriovenous malformations. These lesions cause bleeding, particularly in the nose, gastrointestinal tract and brain. HHT has incomplete penetrance, variable expressivity and genetic heterogeneity. De novo mutations associated with the onset of sporadic HHT have been reported. This Utility Gene Test was prepared on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

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Growth and regression of arteriovenous malformations in a patient with hereditary hemorrhagic telangiectasia

Journal of Neurosurgery ◽

10.3171/jns.2007.106.3.470 ◽

2007 ◽

Vol 106 (3) ◽

pp. 470-477 ◽

Cited By ~ 40

Author(s):

Rose Du ◽

Tomoki Hashimoto ◽

Tarik Tihan ◽

William L. Young ◽

Victor Perry ◽

...

Keyword(s):

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

De Novo ◽

Chromosome 9 ◽

Single Patient ◽

Surgical Specimen ◽

Endothelial Proliferation ◽

History Of ◽

Underlying Pathophysiology

✓ Data on the growth, regression, and de novo formation of arteriovenous malformations (AVMs) suggest that some of these lesions are not formed and developed only during embryogenesis. Patients with hereditary hemorrhagic telangiectasia (HHT) have a genetic propensity to form AVMs. The authors report on the growth and regression of AVMs in a single patient with HHT. This 26-day-old boy with a family history of HHT1 and a mutation in ENG on chromosome 9 presented with a generalized seizure. Results of computed tomography revealed a left frontoparietal intra-parenchymal hemorrhage. Cerebral angiography revealed multiple AVMs. Follow-up angiograms obtained 5 months later showed both growth and regression of the AVMs. A craniotomy was performed for complete resection of the left parietal AVM. Histopathological features of the surgical specimen were examined. Active angiogenesis, as indicated by increased endothelial proliferation, might be a part of the underlying pathophysiology of the growth and regression of AVMs.

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Hereditary hemorrhagic telangiectasia diagnosed by enteroscopy: a case report

Journal of International Medical Research ◽

10.1177/03000605211067391 ◽

2021 ◽

Vol 49 (12) ◽

pp. 030006052110673

Author(s):

Margarita Rey ◽

Johana Milena Salazar ◽

Drixie Dalyla Leal ◽

Fernando Sierra ◽

Erika Pérez ◽

...

Keyword(s):

Case Report ◽

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

Laboratory Tests ◽

Autosomal Dominant ◽

Double Balloon Enteroscopy ◽

Multisystemic Disease ◽

History Of ◽

Patient’S History ◽

Endoscopic Methods

Hereditary hemorrhagic telangiectasia (HHT) is a very rare autosomal dominant multisystemic disease. Patients with this disease usually present with punctate mucocutaneous telangiectasias and arteriovenous malformations. The diagnostic criteria currently in use are the Curaçao criteria. HHT is considered a clinical diagnosis; thus, no imaging or preclinical laboratory is mandatory, and diagnosis and management are performed according to the experience of the treating team. We herein describe a 58-year-old man with no significant medical history who presented with a 15-day history of intermittent hematochezia. He was admitted to the hospital and underwent a series of laboratory tests, including colonoscopy, which showed normal results. Therefore, the patient was discharged with a diagnosis of gastrointestinal bleeding. During his second visit to the emergency room, the doctors requested video capsule endoscopy because of the patient’s history, and a diagnosis of HHT was made. The entire approach and treatment were completed with antegrade double-balloon enteroscopy. This case highlights the importance of endoscopic methods for timely diagnosis and proper management.

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Angioarchitecture of Hereditary Arteriovenous Malformations

Seminars in Interventional Radiology ◽

10.1055/s-0037-1604298 ◽

2017 ◽

Vol 34 (03) ◽

pp. 250-257 ◽

Cited By ~ 5

Author(s):

Patricia Burrows

Keyword(s):

Arteriovenous Malformation ◽

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

Autosomal Dominant ◽

Imaging Biomarkers ◽

Molecular Pathways ◽

Imaging Features ◽

Dominant Inheritance ◽

Appropriate Treatment ◽

Hereditary Conditions

AbstractThis article describes three hereditary conditions known to be associated with arteriovenous malformation (AVM), along with their clinical and imaging features and angiographic angioarchitecture. Hereditary hemorrhagic telangiectasia, capillary malformation–AVM (CM–AVM), and PTEN tumor hamartoma syndrome are conditions with autosomal dominant inheritance, caused by mutations in different molecular pathways, which frequently present with symptomatic AVMs. Imaging biomarkers, including sites of predilection, angioarchitecture, and tissue overgrowth patterns, are helpful in identifying these patients and selecting appropriate treatment.

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SMAD4 juvenile polyposis syndrome and hereditary haemorrhagic telangiectasia presenting in a middle-aged man as a large fungating gastric mass, polyposis in both upper and lower GI tract and iron deficiency anaemia, with no known family history

BMJ Case Reports ◽

10.1136/bcr-2020-236855 ◽

2020 ◽

Vol 13 (12) ◽

pp. e236855

Author(s):

Wendy Chang ◽

Patricia Renaut ◽

Casper Pretorius

Keyword(s):

Family History ◽

Autosomal Dominant ◽

Signs And Symptoms ◽

Juvenile Polyposis ◽

Hereditary Haemorrhagic Telangiectasia ◽

Gi Tract ◽

Juvenile Polyposis Syndrome ◽

Polyposis Syndrome ◽

History Of ◽

Gastric Mass

Juvenile polyposis syndrome (JPS) and hereditary haemorrhagic telangiectasia (HHT) are rare autosomal dominant diseases, where symptoms manifest at childhood. A 32-year-old man with no family history of JPS or HHT with SMAD4 gene mutation who developed signs and symptoms only at the age of 32, when he was an adult. In this article, we highlight the steps taken to diagnose this rare pathology, explain its pathophysiology and management.

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Novel SCN5A p.Val1667Asp Missense Variant Segregation and Characterization in a Family with Severe Brugada Syndrome and Multiple Sudden Deaths

International Journal of Molecular Sciences ◽

10.3390/ijms22094700 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4700

Author(s):

Michelle M. Monasky ◽

Emanuele Micaglio ◽

Giuseppe Ciconte ◽

Ilaria Rivolta ◽

Valeria Borrelli ◽

...

Keyword(s):

Genetic Testing ◽

Family History ◽

Risk Stratification ◽

Brugada Syndrome ◽

Electrophysiological Study ◽

Functional Characterization ◽

The Family ◽

Novel Variant ◽

History Of ◽

Scn5a Gene

Genetic testing in Brugada syndrome (BrS) is still not considered to be useful for clinical management of patients in the majority of cases, due to the current lack of understanding about the effect of specific variants. Additionally, family history of sudden death is generally not considered useful for arrhythmic risk stratification. We sought to demonstrate the usefulness of genetic testing and family history in diagnosis and risk stratification. The family history was collected for a proband who presented with a personal history of aborted cardiac arrest and in whom a novel variant in the SCN5A gene was found. Living family members underwent ajmaline testing, electrophysiological study, and genetic testing to determine genotype-phenotype segregation, if any. Patch-clamp experiments on transfected human embryonic kidney 293 cells enabled the functional characterization of the SCN5A novel variant in vitro. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.5000T>A (p.Val1667Asp) in the SCN5A gene, and demonstrate its segregation with a severe form of BrS and multiple sudden deaths. Functional data revealed a loss of function of the protein affected by the variant. These results provide the first disease association with this variant and demonstrate the usefulness of genetic testing for diagnosis and risk stratification in certain patients. This study also demonstrates the usefulness of collecting the family history, which can assist in understanding the severity of the disease in certain situations and confirm the importance of the functional studies to distinguish between pathogenic mutations and harmless genetic variants.

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Prevalence and characteristics of brain arteriovenous malformations in hereditary hemorrhagic telangiectasia: a systematic review and meta-analysis

Journal of Neurosurgery ◽

10.3171/2016.7.jns16847 ◽

2017 ◽

Vol 127 (2) ◽

pp. 302-310 ◽

Cited By ~ 20

Author(s):

Waleed Brinjikji ◽

Vivek N. Iyer ◽

Christopher P. Wood ◽

Giuseppe Lanzino

Keyword(s):

Systematic Review ◽

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

Clinical Presentation ◽

Meta Analysis ◽

Prevalence Rates ◽

Brain Avm ◽

Martin Grade ◽

Cerebral Avms ◽

Brain Avms

OBJECTIVEPatients with hereditary hemorrhagic telangiectasia (HHT) are known to suffer from high rates of cerebral arteriovenous malformations (AVMs). The authors performed a systematic review and meta-analysis of the literature examining prevalence rates, characteristics, and clinical presentation of cerebral AVMs in the HHT population.METHODSTo identify studies on AVM prevalence and characteristics in the HHT population, 4 databases (MEDLINE, EMBASE, Scopus and Web of Science) were searched by a reference librarian with over 30 years experience in systematic reviews and meta-analysis. The search period was January 1, 1990–March 2016. The following search terms were used: hereditary hemorrhagic telangiectasia, Osler-Weber-Rendu syndrome, AVM, brain AVM, arteriovenous malformation, arteriovenous fistula, prevalence, and epidemiology. The authors identified studies that examined the prevalence rates, characteristics, and clinical presentation of cerebral AVMs in patients with HHT. They assessed overall AVM prevalence rates as well as prevalence rates by age, sex, HHT type, and country/region. They also systematically reviewed the characteristics of AVMs, including rupture status, location, clinical presentation, angioarchitecture, and Spetzler-Martin grade. Data were analyzed using a random-effects meta-analysis model.RESULTSThirty-nine studies were included in this meta-analysis. Thirty studies examined brain AVM prevalence rates in various HHT patient populations, and 18 studies examined AVM clinical and angiographic characteristics (9 studies examined both prevalence rates and AVM characteristics). The prevalence of brain AVMs in HHT patients was 10.4% (95% CI 7.9%–13.0%) with no significant difference between males (8.5%, 95% CI 4.9%–12.0%) and females (11.0%, 95% CI 5.9%–16.1%). Patients with HHT Type 1 (HHT1) had a significantly higher brain AVM prevalence (13.4%, 95% CI 9.5%–17.4%) compared with those with HHT Type 2 (HHT2) (2.4%, 95% CI 1.0%–3.8%) (p < 0.0001). In 55.2% (95% CI 38.3%–72.1%) of cases, the AVMs were symptomatic. Spetzler-Martin grade was 2 or less in 86.9% (95% CI 67.5%–95.2%) of patients.CONCLUSIONSThe prevalence of brain AVMs in the HHT population is about 10%. HHT1 patients are significantly more likely to have brain AVMs than HHT2 patients. Most AVMs in the HHT population are symptomatic. The Spetzler-Martin grade for these lesions is 2 or less in nearly 90% of patients.

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