Pleomorphic Parotid Adenoma in a Child Affected with Cri du Chat Syndrome: Clinical, Cytogenetic, and Molecular Analysis.

Salivary gland pleomorphic adenoma (SGPA) is the most common type of benign epithelial tumor; it is observed more commonly in females (with a female-to-male ratio of 1.43:1), and the age at diagnosis ranges between 40 and 59 years, with only 2% of cases diagnosed before age 18. Cri du Chat (CdC) is a rare syndrome caused by deletions of various sizes in the short arm of chromosome 5.

Silicone septal splint for recurrent epistaxis in HHT patients: experience of a national referral centre.

Objective: To report our experience in the use of silicone septal splint for recurrent severe epistaxis in hereditary haemorrhagic telangiectasia patients (HHT).

Methods: This is a descriptive analysis carried out at the Otorhinolaryngology Department of Fondazione IRCCS Policlinico San Matteo in Pavia, a reference centre for the treatment and diagnosis of HHT. We retrospectively evaluated HHT patients who underwent silicone septal splint positioning after the endoscopic surgical treatment of epistaxis from 2000 to 2022.

Hereditary Hemorrhagic Telangiectasia in Pediatric Age: Focus on Genetics and Diagnosis.

Hereditary Hemorrhagic Telangiectasia (HHT) or Rendu-Osler-Weber Syndrome (ROW) is an autosomal dominant vascular disease, with an estimated prevalence of 1:5000. Genes associated with HHT are , , , and , all encoding for proteins involved in the TGFβ/BMPs signaling pathway. The clinical diagnosis of HHT is made according to the "Curaçao Criteria," based on the main features of the disease: recurrent and spontaneous epistaxis, muco-cutaneous telangiectases, arteriovenous malformations in the lungs, liver, and brain, and familiarity.

Endoglin and Systemic Sclerosis: A PRISMA-driven systematic review.

Background: Systemic Sclerosis (SSc) is a rare autoimmune disease whose pathogenesis is still poorly understood. The Transforming Growth Factor β superfamily is considered pivotal and a crucial role has been suggested for the type III receptor, Endoglin (ENG). The aim of this systematic review is to investigate and combine the current clinical and molecular available data, to suggest novel hints for further studies.

Hereditary hemorrhagic telangiectasia: First demonstration of a founder effect in Italy; the ACVRL1 c.289_294del variant originated in the country of Bergamo 200 years ago.

Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder, affecting 1:5000 individuals worldwide. All the genes associated to the disease (ENG, ACVRL1, SMAD4, GDF2) belong to the TGF-β/BMPs signaling pathway. We found 19 HHT unrelated families, coming from a Northern Italy region and sharing the ACVRL1 in-frame deletion c.

BMPR2 mutations and response to inhaled or parenteral prostanoids: a case series.

Whether mutations in the BMPR2 gene may influence the response to PAH-specific therapies has not yet been investigated. In this study, in 13 idiopathic, heritable or anorexigen-associated PAH patients, in whom treatment escalation was performed by adding a prostanoid, a greater haemodynamic improvement was observed in BMPR2-negative than in BMPR2-positive patients.

Endoscopic surgical treatment of epistaxis in hereditary haemorrhagic telangiectasia: our experience.

Objectives: Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease characterised by epistaxis. Surgical procedures for epistaxis vary from diathermocoagulation to nasal closure. The aim of this paper is to report our experience in endoscopic surgical management of epistaxis in HHT patients.

Characterization of a mutation in the zona pellucida module of Endoglin that causes Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a vascular rare disease characterized by nose and gastrointestinal bleeding, skin and mucosa telangiectasias, and arteriovenous malformations in internal organs. HHT shows an autosomal dominant inheritance and a worldwide prevalence of approximately 1:5000 individuals. In >80% of patients, HHT is caused by mutations in either ENG (HHT1) or ACVRL1 (HHT2) genes, which code for the membrane proteins Endoglin and Activin A Receptor Type II-Like Kinase 1 (ALK1), respectively, both belonging to the TGF-β/BMP signaling pathway.

Shwachman-Diamond syndrome with clonal interstitial deletion of the long arm of chromosome 20 in bone marrow: haematological features, prognosis and genomic instability.

In Shwachman-Diamond syndrome (SDS), deletion of the long arm of chromosome 20, del(20)(q), often acquired in bone marrow (BM), may imply a lower risk of developing myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), due to the loss of the EIF6 gene. The genes L3MBTL1 and SGK2, also on chromosome 20, are in a cluster of imprinted genes, and their loss implies dysregulation of BM function. We report here the results of array comparative genomic hybridization (a-CGH) performed on BM DNA of six patients which confirmed the consistent loss of EIF6 gene.

Different forms of pulmonary hypertension in a family with clinical and genetic evidence for hereditary hemorrhagic teleangectasia type 2.

Hereditary hemorrhagic telangiectasia (HTT) is an autosomal dominant disease, most frequently caused by a mutation in either ENG or ACVRL1, which can be associated with pulmonary arterial hypertension (PAH). In this report, we describe a new unpublished ACVRL1 mutation segregating in three members of the same family, showing three different types of pulmonary hypertension (PH) in the absence of BMPR2 mutations. The first patient has a form of heritable PAH (HPAH) in the absence of hepatic arteriovenous malformations (AVMs); the second one has a severe form of portopulmonary hypertension (PoPAH) associated with multiple hepatic AVMs; the third one has hepatopulmonary syndrome (HPS) with numerous hepatic arteriovenous fistulas and a form of post-capillary PH due to high cardiac output.

Functional analysis of a novel ENG variant in a patient with hereditary hemorrhagic telangiectasia (HHT) identifies a new Sp1 binding-site.

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare disease, with an autosomal dominant inheritance and a worldwide incidence of about 1: 5000 individuals. In >80% of patients, HHT is caused by mutations in either ENG or ACVRL1, which code for ENDOGLIN and Activin A Receptor Type II-Like Kinase 1 (ALK1), belonging to the TGF-β/BMP signalling pathway. Typical HHT clinical features are mucocutaneous telangiectases, arteriovenous malformations, spontaneous and recurrent epistaxis, as well as gastrointestinal bleedings.

Fluorescein-guided intraoperative endoscopy in patients with hereditary hemorrhagic telangiectasia: first impressions.

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease that results in mucocutaneous telangiectasias and arteriovenous visceral malformations. Nasal telangiectasias lead to recurrent epistaxis, which affects up to 96% of patients. Different morphologic classifications and methods of visualization of nasal lesions have been described in the literature.

Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary haemorrhagic telangiectasia: results of a non-randomised, single-centre, phase 2 study.

Background: Hereditary haemorrhagic telangiectasia is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anaemia. Several therapeutic approaches have been investigated, but they are mostly palliative and have had variable results.

Increase of circulating endothelial cells in patients with Hereditary Hemorrhagic Telangiectasia.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by vascular malformations. The genes known to be associated with HHT include ENG (HHT1), ACVRL1 (HHT2) and SMAD4 (JPHT). It has been reported that circulating CD34(+) cell subsets repair damaged vessels.

Activin Receptor-like kinase 1: a novel anti-angiogenesis target from TGF-β family.

Anti-angiogenic therapy represents a very promising approach in cancer treatment, as most tumors needs to be supplied by a functional vascular network in order to grow beyond the local boundaries and metastatize. The accessibility of vessels to drug delivery and the broad spectrum of cancers treatable with the same compound have arisen interest in research of suitable molecules, with several, especially targeting the VEGF pathway, entered in clinical trials and approved by the Food and Drug Administration. Despite good results, the major hurdle resides in the limited duration of an effective clinical response before tumors start to grow again.

HHT diagnosis by Mid-infrared spectroscopy and artificial neural network analysis.

Background: The vascular disorder Hereditary Hemorrhagic Telangiectasia (HHT) is in general an inherited disease caused by mutations in the TGF-β/BMP receptors endoglin or ALK1 or in rare cases by mutations of the TGF-β signal transducer protein Smad4 leading to the combined syndrome of juvenile polyposis and HHT. HHT is characterized by several clinical symptoms like spontaneous and recurrent epistaxis, multiple telangiectases at sites like lips, oral cavity, fingers, nose, and visceral lesions like gastrointestinal telangiectasia, pulmonary, hepatic, cerebral or spinal arteriovenous malformations. The disease shows an inter- and intra-family variability in penetrance as well as symptoms from mild to life threatening.

Endoscopic evaluation of gastrointestinal tract in patients with hereditary hemorrhagic telangiectasia and correlation with their genotypes.

Purpose: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular dysplasia characterized by telangiectases and arteriovenous malformations. Three causative genes are known: ENG (HHT-1), ACVRL1 (HHT-2), and SMAD4 (mutated in HHT in association with juvenile polyposis). Gastrointestinal bleeding is the most common symptom after epistaxis.

Hereditary Hemorrhagic Telangiectasia: Breakpoint Characterization of a Novel Large Deletion in ACVRL1 Suggests the Causing Mechanism.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia. Mutations in either ENG or ACVRL1 account for around 85% of cases, and 10% are large deletions and duplications. Here we present a large novel deletion in ACVRL1 gene and its molecular characterization in a 3 generation Italian family.

Argon plasma coagulation is an effective treatment for hereditary hemorrhagic telangiectasia patients with severe nosebleeds.

Conclusions: In contrast to the current trend according to which the treatment of hereditary hemorrhagic telangiectasia (HHT) epistaxis depends on clinical severity, argon plasma coagulation (APC) has also proven to be effective as a first-line procedure in patients with severe nosebleeds. Furthermore, with this approach patients are free from requirements for blood transfusions for a long time in the vast majority of cases.

Objective: The aim of this study was to test the efficacy of APC treatment as a first-line procedure in HHT patients affected by severe epistaxis.

Bioinformatic analysis of pathogenic missense mutations of activin receptor like kinase 1 ectodomain.

Activin A receptor, type II-like kinase 1 (also called ALK1), is a serine-threonine kinase predominantly expressed on endothelial cells surface. Mutations in its ACVRL1 encoding gene (12q11-14) cause type 2 Hereditary Haemorrhagic Telangiectasia (HHT2), an autosomal dominant multisystem vascular dysplasia. The study of the structural effects of mutations is crucial to understand their pathogenic mechanism.

Natural history and outcome of hepatic vascular malformations in a large cohort of patients with hereditary hemorrhagic teleangiectasia.

Background: Hereditary hemorrhagic telangiectasia is a genetic disease characterized by teleangiectasias involving virtually every organ. There are limited data in the literature regarding the natural history of liver vascular malformations in hemorrhagic telangiectasia and their associated morbidity and mortality.

Aim: This prospective cohort study sought to assess the outcome of liver involvement in hereditary hemorrhagic telangiectasia patients.

Overlapping spectra of SMAD4 mutations in juvenile polyposis (JP) and JP-HHT syndrome.

Juvenile polyposis (JP) and hereditary hemorrhagic telangiectasia (HHT) are clinically distinct diseases caused by mutations in SMAD4 and BMPR1A (for JP) and endoglin and ALK1 (for HHT). Recently, a combined syndrome of JP-HHT was described that is also caused by mutations in SMAD4. Although both JP and JP-HHT are caused by SMAD4 mutations, a possible genotype:phenotype correlation was noted as all of the SMAD4 mutations in the JP-HHT patients were clustered in the COOH-terminal MH2 domain of the protein.