Table 2.

A Comprehensive overview of key genes in hereditary thoracic aortic aneurysm and dissection

Clinical grade	HTAAD genes panel	Protein	%-pathogenic varianta	Syndrome
CAT A1/A2 definitive/ strong	ACTA2	Smooth muscle alpha 2 actin	+  +  +	Multiple SMC dysfunction syndrome
	COL3A1	Collagen alpha 1(III) chain	+  +  +	Ehlers-Danlos syndrome type IV
	FBN1	Fibrillin-1	+  +  +	Marfan syndrome
	SMAD3	SMAD family member 3	+  +  +	Loeys-Dietz, aneurysms osteoarthritis syndrome
	TGFβ2	Transforming growth factor beta-2	+  +  +	Loeys-Dietz syndrome
	TGFBR1	Transforming growth factor beta receptor 1	+  +  +	Loeys-Dietz syndrome
	MYH11	Smooth muscle-myosin heavy chain 11	+  +  +	Familial aortic aneurysm
	MYLK	Myosin light chain kinase	+  +  +	Familial aortic aneurysm
	LOX	Lysyl oxidase	+  +	Not yet classified
	PRKG1	Protein kinase, cGMP-dependent 1	+  +	Familial aortic aneurysm
	EFEMP2	Fibulin 4	+  +	Cutis laxa type Ib
CAT B moderate/ limited	ELN	Tropoelastin	+	Cutis laxa, Williams Syndrome
	FBN2	Fibrillin-2	+  +  +	Congenital contractural archnodactyly
	FLNA	Filamin A	+  +	Periventricular nodular heterotopia
	NOTCH1	Notch1	+  +	BAV with aneurysm
	SLC2A10	Glucose transporter protein type 10	+  +  +	Arterial tortuosity syndrome
	SMAD4	SMAD family member 4	+  +	JP/HHT syndrome
	SKI	SKI proto-oncogene	+  +  +	Shprintzen-Goldberg syndrome
	TGFB3	Transforming growth factor beta-3	+  +	Loeys-Dietz syndrome
Undetermined	BGN	Small leucine-rich proteoglycan	+  +	Meester-loeys syndrome
	FOXE3	Forkhead box E3	+  +	Familial aortic aneurysm
	MAT2A	Methionine adenosyltransferase IIA	+  +	Familial aortic aneurysm
	MFAP2	Microfibril-associated protein 2	+  +	Familial aortic aneurysm
	SMAD2	SMAD family member 2	+	Not yet classified

^a%- pathogenic variant: ( +) 1–25%; (+ +) 26–75%; (+ + +) 75–100%