Clinical Features,Imaging Characteristics,and Hereditary Analysis Of Two Hereditary Hemorrhagic Telangiectasia Families

Objective:To analyze the clinical features and imaging characteristics of two clinically confirmed hereditary hemorrhagic telangiectasia(HHT)probands and their families.A proband and her family members were screened for pathogenic genes,and the relationship between mutations and the incidence of HHT was further explored,in order to provide a reference for the early diagnosis and treatment of HHT.Finally,the existing clinical diagnostic criteria were discussed based on the two families.Methods:The subjects were two proband patients and their families diagnosed with hereditary hemorrhagic telangiectasia in the First Affiliated Hospital of Dali University from October 2021 to October 2022,there are 35 people in the F1 family and 9 people in the F2 lineage,for a total of 44 people.The study was approved by the Ethics Committee of the First Affiliated Hospital of Dali University,detailed clinical examination and imaging examinations were performed after signing the relevant informed consent forms between the two proband and their family members,peripheral venous blood was drawn from two family prospectors and their family members at the same time for personal total exon testing.According to the results of imaging examinations,9 patients screened for pulmonary arteriovenous malformation(PAVM)in two families were divided into HHT clinical feature group(n=4)and no HHT clinical feature group(n=5)according to the clinical features of HHT,and the imaging features between the two groups were compared and analyzed.The clinical data,imaging data and hereditary characteristics of the two families were reviewed.Results : The proband lineage F1 includes 4 generations with a total of 35 family members,and the family F2 consists of 3 generations with a total of 9 family members.4 cases of family F1 showed the clinical features of HHT,2 women and 2males,each generation had individual onset,conforming to the autosomal dominant inheritance pattern,and 8 cases were screened for pulmonary arteriovenous malformations by imaging examination.3 cases in the family F2 showed the clinical features of HHT,2 women and 1 male,each generation had individual onset,conforming to the autosomal dominant inheritance pattern,1 case showed pulmonary arteriovenous malformation on imaging with splenic involvement,and 1 case had cerebrovascular malformation rupture and bleeding.According to the clinical diagnostic criteria,5 patients of two families who met three or more clinical diagnostic criteria could be diagnosed as HHT,and 7 patients met two diagnostic criteria and were suspected to be HHT.5 cases of confirmed HHT imaging in 2 clinically confirmed families showed visceral vascular malformation,and the sensitivity of imaging diagnosis was 100%.Among the 9 patients with pulmonary arteriovenous malformations,there was no difference in gender and age of the HHT clinical feature group and the patients without HHT clinical features(P=0.357,P=0.720).There was no significant difference in the number of lesions,signs of vascular pedicels,ground-glass changes,and the maximum diameter of the feeding artery and draining vein between two groups(P=0.167,P=0.278,P=0.405,P=0.135,P=0.165).The maximum average diameter of the malformed vascular mass is(2.03±2.58)cm.The maximum diameter of the tumor sac in the group with HHT clinical features was significantly greater than that in the group without HHT clinical features(P<0.05).Family F1 single-gene genetic disease genetic testing-whole exon test,found some insufficient evidence of pathogenic disease,but did not exclude the possible genetic variation of the disease;family F2 underwent single-gene genetic disease genetic testing-whole exon detection,in which F2 prospectors showed the presence of ENG gene c.360+1G>A(chr9:130591965)mutation.Conclusion : There are large inter-individual differences in presentation,system involvement,clinical features,and prognosis of patients with hereditary hemorrhagic telangiectasia within the same family and/or between families,which makes the early clinical diagnosis and treatment of the disease difficult,and the overall prognosis of patients with related complications is not good.Imaging can accurately show visceral involvement,and its high sensitivity and specificity facilitate the early diagnosis of HHT,thereby facilitating further treatment.This study reported the first patient with HHT complicated by splenic littoral cell angioma(LCA),but its relationship with HHT is unclear.The clinically relevant symptoms of PAVM patients with HHT clinical features are related to the size of malformed vascular masses.The evidence of pathogenic disease found in family F1 is insufficient,but genetic variants that may cause disease may not be ruled out,which may further enrich the screening content of HHT,existing clinical diagnostic criteria have limitations in the diagnosis of HHT patients and family members,and when the family history criterion is met,the diagnosis of HHT may be confirmed when vascular lesions appear.