Table 8.

Inherited/germline conditions involving arteriovenous malformations.

Associated malformation or syndrome	Inheritance	Clinical phenotype	Candidate gene	Protein function or suspected role (if known)	Clinical work-up	References
Hereditary Hemorrhagic Telangiectasia (HHT) aka Osler-Weber-Rendu Syndrome	AD	• Telangiectasias (lip, tongue, buccal mucosa, face, chest, and fingers) • AVMs throughout multiple sites including cerebral, pulmonary, gastrointestinal, and hepatic • Most common clinic manifestation epistaxis (starting age 12 usually) • Iron deficiency anemia • Heart failure • Stroke • GI bleed 25%, commonly after 50	ENG, ALK1/ACVRL1, GDF2 SMAD4/MADH4	• TGF-β signaling pathway	• CBC/iron studies • Sitting and supine pulse oximetry every 1–2 years during childhood • Contrast echo every 5 years by age 10 • Periodic endoscopy/colonoscopy to rule out GI polyps and malignant change of juvenile polyps • ENT evaluation • Brain MRI/MRA in infancy and after puberty • Liver US • Genetic testing and counseling • Antibiotic prophylaxis for dental and invasive procedure • Filter on IV lines to prevent bubbles if pulmonary AVM is present	(3, 58, 59)
CM-AVM1*	AD or sporadic	• Small, multifocal CMs often accompanied by a pale halo • 30% of cases associated with additional deeper, fast-flow AVMs	RASA1 EPHB4	• Loss of function; encodes Ras GTPase activating protein p120RasGAP	• Brain/Spine imaging • Genetic testing and counseling • Screening echocardiography • X-rays for leg length discrepancy • ENT evaluation if epistaxis • US shows fast-flow lesion	(3, 9, 11, 15, 20, 21)
CM-AVM2*	Unknown, likely AD	• Small telangiectasias around the lips and on upper thorax • Less frequently cerebral AVMs	EPHB4	• Loss of function mutation. Transmembrane receptor preferentially expressed in endothelial cells, acts via RAS/MAPK pathway	• Brain/Spine imaging • Genetic testing and counseling • Screening echocardiography • X-rays for leg length discrepancy • ENT evaluation if epistaxis	(12, 20, 21)

^*Note that CM-AVM is classified under both capillary and arteriovenous malformation.