Clinicoradiological and Genetic Analyses of Three Thai
Families with Hereditary Hemorrhagic Telangiectasia in
Ramathibodi Hospital
Sirintara (Pongpech) Singhara Na Ayudhaya MD1, Thipwimol Tim-Aroon MD2, Chaiyos Khongkhatithum MD2,
Duangrurdee Wattanasirichaigoon MD2, Ekachat Chanthanaphak MD1, Chai Kobkitsuksakul MD1,
Kittiphop Somboonnithiphol MD3
Affiliation :
1 Department of Radiology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
2 Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
3 Department of Radiology, Faculty of Medicine, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand
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 con(cid:976)irmed 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 (cid:976)ive 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 (cid:976)istula [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 (cid:976)irst 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
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