Objective: To study the clinical manifestations, radiological imaging, and genetic mutations of Hereditary Hemorrhagic Telangiectasia [HHT] patients in Ramathibodi Hospital.

Materials and Methods: Clinical phenotypes and radiological imaging of patients and family members were reviewed. Mutation analyses were initially performed in the probands by next generation sequencing, focusing on four known genes causing HHT, endoglin (ENG), activin A receptor type II like 1 (ACVRL1; ALK1), SMAD family member 4 (SMAD4), and growth/differentiation factor 2 (GDF2). Pathogenic variants were confirmed by conventional sequencing.

Results: Seven symptomatic HHT patients in three families were studied. Spontaneous recurrent epistaxis was noted in all patients with an average age of onset of about 13 years. Mucocutaneous telangiectasia was observed in six patients. Pulmonary arteriovenous malformations [AVMs] were noted in five patients. One symptomatic case had a large pulmonary AVM that needed embolization. Brain AVMs were detected in four patients. All types of HHT associated brain AVMs were observed and included capillary vascular malformations/micro-AVMs in two cases, nidal type brain AVMs in two cases, and pial arteriovenous fistula [AVF] in one case. Osteodural AVF at clivus was detected in one patient. Spinal cord AVM at thoracic level was found in one patient during screening for pulmonary AVMs. The pial AVF, osteodural AVF, and spinal cord AVM were successfully treated by endovascular approaches without complications. All three families were found to have mutations in ENG gene and included one known mutation (c.1311+5G>A) and two noval mutations (c.1429-5T>G and c.1533_1534 delGGinsC).

Conclusion: This presented study is the first HHT series in Thailand with comprehensive clinicoradiological and genetic analyses. Various clinical manifestations among family members were observed. Pulmonary AVMs and central nervous system [CNS] AVMs are the major causes of morbidity in these patients. Only ENG gene was found to be a cause of HHT in the presented study.

Keywords: Hereditary hemorrhagic telangiectasia, HHT, ENG gene, Mutation