ENG and hereditary hemorrhagic telangiectasia: Furthermore, as HHT1 patients carry one wild-type copy of the ENG gene, the current premise is that a second hit (somatic loss of function mutation in normal ENG allele) is required to generate a vascular location that is at risk for detrimental remodeling to generate AVMs.13,39 In addition, the vascular lesions in HHT patients generally develop in tissues exposed to environmental or inflammatory insults (lung, skin, and gastrointestinal tract) and liver (responsible for removing toxins of environmental origin).