Prenatal diagnosis of pulmonary arteriovenous malformations with a postnatal diagnosis of Osler-Weber-Rendu syndrome.

Hereditary Hemorrhagic Telangiectasia (HHT), commonly known as Osler-Weber-Rendu disease, is an autosomal dominant multisystemic vascular disease associated with approximately 70% of cases of pulmonary arteriovenous malformations (PAVMs). Prenatal cases of PAVMs typically present with pulmonary vein dilatation on ultrasonography. This study presents a prenatal diagnosis of PAVMs with enlarged right pulmonary vein, cardiomegaly, cystic-appearing areas in the right lung and subsequent confirmation of Osler-Weber-Rendu syndrome using autopsy and whole exom sequencing.

De Novo Brain Vascular Malformations in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND: Approximately 10% of people with hereditary hemorrhagic telangiectasia (HHT) have brain vascular malformations (VMs). Few reports describe de novo brain VM formation. International HHT Guidelines recommend initial brain VM screening upon HHT diagnosis in children but do not address rescreening. We aimed to confirm whether brain VMs can form de novo in patients with HHT. METHODS: The Brain Vascular Malformation Consortium HHT project is a 17-center longitudinal study enrolling patients since 2010. We analyzed the database for de novo VMs defined as those detected (1) on follow-up neuroimaging in a patient without previous brain VMs or (2) in a location distinct from previously identified brain VMs and reported those in whom a de novo VM could be confirmed on central neuroimaging review. RESULTS: Of 1909 patients enrolled, 409 (21%) had brain VMs. Seven patients were recorded as having de novo brain VMs, and imaging was available for central review in four. We confirmed that three (0.7% of individuals with brain VMs) had de novo brain VMs (two capillary malformations, one brain arteriovenous malformation) with intervals of six, nine, and 13 years from initial imaging. Two with de novo brain VMs were <18 years. The fourth patient, a child, did not have a de novo brain VM but had a radiologically confirmed increase in size of an existing brain arteriovenous malformation. CONCLUSIONS: Brain VMs can, albeit rarely, form de novo in patients with HHT. Given the potential risk of hemorrhage from brain VMs, regular rescreening in patients with HHT may be warranted.

Brain AVM compactness score in children with hereditary hemorrhagic telangiectasia.

OBJECTIVE: The brain arteriovenous malformation (BAVM) nidus compactness score (CS), determined on angiography, predicts BAVM recurrence after surgical resection among children with sporadic BAVMs. We measured the angiographic CS for BAVMs among children with hereditary hemorrhagic telangiectasia (HHT) to determine CS characteristics in this population. METHODS: A pediatric interventional neuroradiologist reviewed angiograms to determine the CS of BAVMs in children with HHT recruited to the BVMC. CS is based on overall nidus and perinidal anomalous vessel compactness. CS categories included 1 = diffuse nidus, 2 = intermediate nidus, and 3 = compact nidus. RESULTS: Forty-eight of 78 children (61.5%) with HHT and brain vascular malformations had a conventional angiogram; 47 (97.9%) angiograms were available. Fifty-four BAVMs were identified in 40 of these 47 children (85.1%). Of 54 BAVMs in children with HHT, CS was 1 in 7 (13%), 2 in 29 (53.7%), and 3 in 18 BAVMs (33.3%) compared with CS of 1 in six (26.1%), 2 in 15 (65.2%), and 3 in 2 BAVMs (8.7%) among 23 previously reported children with sporadic BAVMs, p = 0.045 (Fisher's exact). Seven children with HHT had intracranial hemorrhage: 4 had CS = 3, 1 had CS = 2, and 2 had CS = 1. CONCLUSIONS: A range of CSs exists across HHT BAVMs, suggesting it may be an angiographic measure of interest for future studies of BAVM recurrence and hemorrhage risk. Children with HHT may have more compact niduses compared to children with sporadic BAVMs. Additional research should determine whether CS affects hemorrhage risk or post-surgical recurrence risk in HHT-associated BAVMs, which could be used to direct BAVM treatment.

Hereditary hemorrhagic telangiectasia with hepatic arteriovenous shunt diagnosed due to liver damage.

A 53-year-old woman was diagnosed with liver dysfunction in August 20XX. Computed tomography (CT) revealed multiple hepatic AV shunts, and she was placed under observation. In March 20XX + 3, she developed back pain, and CT performed during an emergency hospital visit showed evidence of intrahepatic bile duct dilatation. She was referred to our gastroenterology department in May 20XX + 3. We conducted investigations on suspicion of hereditary hemorrhagic telangiectasia (HHT) with hepatic AV shunting based on contrast-enhanced CT performed at another hospital. HHT is generally discovered due to epistaxis, but there are also cases where it is diagnosed during examination of liver damage.

Preliminary Experience with a Low-Profile High-Density Braid Occluder for Transcatheter Embolization of Pulmonary Arteriovenous Malformations.

This brief report describes safety, technical feasibility, and early treatment effectiveness of the low-profile braided occluder (LOBO; Okami Medical, San Diego, Caliornia) for embolization of 9 pulmonary arteriovenous malformations (PAVMs) in 4 patients (3 female and 1 male; age range: 33 to 63 years; 3 patients showed positive results for hereditary hemorrhagic telangiectasia genes). A total of 10 occluders were deployed in 10 vessels (median treated vessel diameters, 3 and 4 mm for LOBO-3 and LOBO-5 groups, respectively). All devices were successfully deployed into the feeder pulmonary arteries, achieving complete cessation of flow. There were no severe adverse events or device migrations. Available short-term follow-up computed tomography (6 PAVMs: median, 7 months; range, 1.5-7 months) demonstrated complete occlusion without persistence or recanalization. The early experience of embolization of PAVMs using a low-profile braided occluder showed it to be safe and effective. Further studies with larger cohorts and longer follow-up periods are warranted.

Hepatic Vascular Variants in Hereditary Haemorrhagic Telangiectasia: Imaging findings.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterised by vascular dysplasia. Hepatic vascular malformations (VMs) range from small telangiectases to significant vascular shunting. Here we report two cases of HHT. Case 1 had diffuse ectasia of the hepatic artery along its intrahepatic and extrahepatic course with a hepatic arterial aneurysm. Case 2 presented with ileal and hepatic telangiectases. Knowledge of these vascular variants is indispensable for clinicians and radiologists in aiding diagnosis and surgical and interventional management.

Prevalence and Characteristics of Intracranial Aneurysms in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND AND PURPOSE: The association between hereditary hemorrhagic telangiectasia and intracranial aneurysms remains controversial. This study evaluated the prevalence and characteristics of intracranial aneurysms in patients with hereditary hemorrhagic telangiectasia with brain vascular malformations. MATERIALS AND METHODS: Between 2007 and 2021, patients enrolled in the Brain Vascular Malformation Consortium with definite hereditary hemorrhagic telangiectasia, the presence of brain vascular malformations, and available angiographic studies of the brain were retrospectively reviewed. Angiographic features of intracranial aneurysms and their relationship to coexisting brain vascular malformations were analyzed. We also examined the association between baseline clinical features and the presence of intracranial aneurysms. RESULTS: One hundred eighty patients were included. A total of 14 intracranial aneurysms were found in 9 (5%) patients, and 4 intracranial aneurysms were considered flow-related aneurysms. Patients with intracranial aneurysms were significantly older than patients without intracranial aneurysms (mean, 48.1 [SD, 18.2] years versus 33.5 [SD, 21.0] years; P = .042). If we excluded flow-related intracranial aneurysms, the prevalence of intracranial aneurysms was 3.3%. All intracranial aneurysms were in the anterior circulation, were unruptured, and had an average maximal diameter of 3.9 (SD, 1.5) mm. No intracranial aneurysms were found in pediatric patients with hereditary hemorrhagic telangiectasia. No statistically significant correlation was observed among other baseline demographics, hereditary hemorrhagic telangiectasia features, and the presence of intracranial aneurysms. CONCLUSIONS: The prevalence of intracranial aneurysms in this large cohort study is comparable with that in the general population and might be increased slightly due to hemodynamic factors associated with shunting brain vascular malformations.

Pulmonary Hypertension Due to High-Output Heart Failure: Hereditary Hemorrhagic Telangiectasia.

Pulmonary hypertension (PH) is a complex disorder that should be managed with a multidisciplinary approach. Although most of the underlying causes of left heart disease can be easily diagnosed with cardiac imaging, some pathologies might necessitate careful investigation to go beyond the obvious. High-output heart failure (HF) due to arteriovenous malformation (AVMs) is an unnoticeable cause for HF and PH. Patients with hepatic AVMs should always be carefully evaluated with regard to hereditary hemorrhagic telangiectasia (HHT) since they can have multiple signs related to the other systems without any symptoms. In this case report, we discussed a patient who was initially diagnosed as PH associated with HF with preserved ejection fraction but eventually was found to have PH associated with high-output HF due to hereditary hemorrhagic telangiectasia (HHT, or Osler Weber Rendu syndrome) after detailed evaluation.

Risk factors and clinical features associated with basal ganglia manganese deposition in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: T1-hyperintensity of the basal ganglia (BG) due to manganese deposition is a known radiologic finding in patients with hereditary hemorrhagic telangiectasia (HHT), but risk factors and associated clinical manifestations are unclear. This study conducted a quantitative analysis of the association of T1-hyperintensity in HHT patients with specific risk factors, signs, and symptoms. METHODS: Patients seen at our center between 2005 and 2020 with a definitive diagnosis of HHT who had an available non-contrast T1-weighted brain MRI were included. Hyperintensity was evaluated using oval regions of interest measurements. The BG: thalamus intensity ratio was used to quantitatively evaluate T1-hyperintensity. Patient laboratory values and clinical findings were collected from electronic medical records. Hyperintensity was analyzed for its association with laboratory values, and clinical findings. Variables were analyzed through regression analysis. RESULTS: A total of 239 patients were included in this study. On 1.5 T scanners, values that were significant on multivariable regression analysis were age (p < .001), hepatic AVMs (p < .001), iron deficiency anemia (p = .0021), and cirrhosis (p = .016). On 3 T scanners, values that were significant on multivariable analysis were hepatic AVMs (p = .0024) and cirrhosis (p = .0056). On 3 T scanners, hyperintensity was significantly associated with tremor (OR = 1.17, p = .033), restless leg syndrome (OR = 1.22, p = .0086), and memory problems (OR = 1.17, p = .046). CONCLUSIONS: BG hyperintensity due to manganese deposition is significantly associated with hepatic risk factors on 1.5 T and 3 T scanners and iron deficiency anemia on 1.5 T scanners. On 3 T scanners, T1-hyperintensity is associated with neuropsychiatric signs and symptoms, such as tremor, restless leg syndrome, and memory problems.

The role of interventional radiology in treatment of patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) also known as Osler-Weber-Rendu disease is a rare autosomal dominant, multi-organ disorder that leads to formation of abnormal vascular connections resulting in devastating and life-threatening complications. Due to its multisystem character, wide range of clinical manifestations and variable expressivity, HHT remains a diagnostic challenge and requires close cooperation of specialists from various medical fields. Interventional radiology plays a key role in the management of this disease, helping maintain the health of HHT patients and minimize the risk of fatal complications. The aim of this article is to review clinical manifestations, diagnostic guidelines and criteria of HHT as well as to present the means of endovascular therapy in the management of HHT patients.

Manifestations of hepatic vascular malformations in hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia is a genetic disease, causing abnormal formations of blood vessels in skin, mucus membranes, lungs, liver, and brain. In the liver, the disease results in shunting of blood, bypassing the capillary bed. Recent studies have shown that the prevalence of liver shunts are more frequent than previously suggested. The patients present with symptoms related to high-output cardiac failure causing dyspnoea and oedema. Liver shunts can be shown using CT-scans and ultrasonography. The only curable treatment is a liver transplant; however, it is the last treatment option, as argued in this review.

A GDF2 missense mutation potentially involved in the pathogenesis of hereditary hemorrhagic telangiectasia: a case report.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disease. ENG and ACVRL1 gene variants account for up to 96% of all cases, while the remaining cases are caused by SMAD4 or GDF2 variants, or by currently undiscovered mutations in coding or non-coding regions. Here, we report a 47-year-old man who presented with duodenal bulb bleeding and chronic anemia. Physical examination also revealed bleeding from the skin and gingiva. His parents were cousins and one brother and one sister died in infancy from anemia and bleeding. Head computed tomography angiography (CTA) revealed a complete fetal posterior cerebral artery located in the left side, and pulmonary CTA showed pulmonary arterial hypertension. The patient was diagnosed with HHT. Peripheral blood was collected for whole-exome sequencing. Sequencing revealed a mutation in the GDF2 gene, which encodes bone morphogenetic protein-9 (BMP-9). The detected variant, c.352A > T(p.Ile118Phe), was predicted to be a neutral polymorphism; however, the patient's plasma BMP-9 levels were greatly reduced; we predicted that this might be caused by the GDF2 variant and might be involved in the HHT pathogenesis. Further research in cell lines and animal models is needed to verify the correlation between this GDF2 variant and the pathogenesis of HHT.

Systemic artery to pulmonary artery aneurysm malformations associated with variants at MCF2L.

Arteriovenous malformations (AVM) are characterized by abnormal vessels connecting arteries and veins resulting in a disruption of normal blood flow. Hereditary hemorrhagic telangiectasia (HHT) is the most common cause of pulmonary AVM characterized by a right to left shunt. Here we describe a distinct malformation where the flow of blood was from a systemic artery to the pulmonary artery (PA) resulting in a left to right shunt instead of the right to left shunt seen in individuals with HHT. This distinct malformation was identified in seven probands, one from a multiplex family containing 10 affected individuals from five generations. To identify the molecular basis of this distinct malformation, we performed exome sequencing (ES) on the seven probands and the affected paternal female cousin from the multiplex family. PhenoDB was used to prioritize candidate causative variants along with burden analysis. We describe the clinical and radiological details of the new systemic artery to PA malformation with or without pulmonary artery aneurysm (SA-PA(A)) and recommend distinct treatment techniques. Moreover, ES analysis revealed possible causative variants identified in three families with variants in a novel candidate disease gene, MCF2L. Further functional studies will be necessary to better understand the molecular mechanisms involved on SA-PA(A) malformation, however our findings suggest that MCF2L is a novel disease gene associated with SA-PA(A).

Application of contrast-enhanced ultrasound in hemothorax of hereditary hemorrhagic telangiectasia: A case report and literature review.

Hereditary hemorrhagic telangiectasis (HHT) is an autosomal dominant hereditary disease, which can lead to abnormal angiogenesis. We performed contrast-enhanced ultrasound (CEUS) in a patient with HHT represented with hemothorax. After targeted embolization, the condition of hemothorax improved. In this case, we explore the use of CEUS to locate the responsible vessel of hemothorax, and found that CEUS could be used as a complementary preoperative method of localization with computed tomography angiography (CTA).

Hepatic involvement in hereditary hemorrhagic telangiectasia mimicking focal nodular hyperplasia.

Accurate diagnosis of hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is important for reducing the risk of complications. Hepatic involvement in HHT is usually asymptomatic, but when present can cause noted morbidity and mortality. A 62-year-old woman presented with moderate upper-abdominal pain and tachycardia. A diagnosis of HHT was made based on the findings of hepatic involvement in a contrast-enhanced abdominal computed tomography (CT) scan, the presence of arteriovenous malformations (AVMs; a.k.a. telangiectasias) on mucocutaneous surfaces, and a history of recurrent epistaxis. Imaging methods are important diagnostic tools in patients suspected of having HHT.