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Thursday 6 January 2011

Hereditary hemorrhagic telangiectasia type 2 (HHT2) is caused by mutation in the ACVRL1 gene (MIM.601284 or ALK1) on chromosome 12q.

Visceral findings of HHT2 included pulmonary arteriovenous malformations (PAVMs) (6%), cerebral AVM (7%), spinal AVM (3%), hepatic AVM (17%), gastrointestinal bleeding due to AVMs (11%), and cirrhosis (3%).

Seventy-two percent of patients had onset of nosebleeds by age 15 years; however, there was overlap in frequency of epistaxis between mutation-negative and mutation-positive individuals. The findings illustrated the extreme phenotypic variability of HHT2 even in those with the same mutation.

Pulmonary hypertension that is clinically and histologically indistinguishable from primary pulmonary hypertension (MIM.178600) has been reported in a subset of patients with hereditary hemorrhagic telangiectasia.


- Conjunctival telangiectases
- Spontaneous, recurrent epistaxis (onset in childhood)
- Lip telangiectases
- Tongue telangiectases
- Palate telangiectases
- Nasal mucosa telangiectases
- Right-to-left shunt
Right-to-left shunt
- Cirrhosis
- Liver arteriovenous malformation
- Gastrointestinal hemorrhage (onset usually 5th-6th decade)
- Angiodysplasia
- Arteriovenous malformation
- Telangiectases (stomach, duodenum, small bowel, colon)
- Melena
- Hematochezia
- Hematemesis
- Nail bed telangiectases
- Fingerpad telangiectases
- Clubbin
- Telangiectases (especially on tongue, lips, palate, face, conjunctiva, trunk, nail beds, fingers, and finger pads)
- Migraine headache
- Brian abscess
- Transient ischemic attack
- Ischemic stroke
- Seizure
- Intracerebral hemorrhage
- Subarachnoid hemorrhage
- Cerebral arteriovenous malformation
- Spinal arteriovenous malformation
- Polycythemia
- Definite diagnosis if 3/4 criteria present (epistaxis, telangiectasia, visceral lesion, or family history)
- Genetic heterogeneity. See HHT1 (187300) caused by mutations in endoglin (ENG, 131195)
- PAVM more frequent in HHT1 than HHT2
- Anemia
- Caused by mutations in the activin receptor-like kinase gene (ALK1, 601284.0001)


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