Table 11.

Surgical Thresholds for Prophylactic Aortic Root and Ascending Aortic Replacement in Loeys-Dietz Syndrome Based on Genetic Variant

COR	LOE (references)	Genetic Variant	Presence of High-Risk Features*	Aortic Diameter (cm)
1	C-LD2	TGFBR1	No	≥4.5
1	C-LD2	TGFBR2	No	≥4.5
2b	C-EO2	TGFBR1	Yes	≥4.0
2a	C-LD1,2	TGFBR2	Yes	≥4.0
2a	C-EO13,16	SMAD3	–	≥4.5†
2b	C-EO5–7	TGFB2 ‡	–	≥4.5†
2b	C-EO9,23	TGFB3	–	≥5.0†

^*Aortic surgery may be recommended at smaller aortic diameters in Loeys-Dietz syndrome attributable to TGFBR1 and TGFBR2 pathogenic variants when there are features that associate with a higher risk of aortic dissection, including: certain specific pathogenic variants; women with TGFBR2 and small body size; severe extra-aortic features (ie, craniosynostosis, cleft palate, hypertelorism, bifid uvula, marked arterial tortuosity, widened scars, and translucent skin); family history of aortic dissection (especially at young age or relatively small aortic diameter); and aortic growth rate >0.3 cm/y.

^†Family history, age, and aortic growth rate also inform surgical thresholds.

^‡Pathogenic variants in the TGFB2 gene are different than variants in the TGFBR2 gene.

COR indicates class of recommendation; and LOE, level of evidence.

Colors correspond to COR and LOE in Table 2.