Aortic Root and Ghent Experimental

Aortic Z scores

PHN:     Z = (D[cm] / BSA^0.5 − mean) / SD,   BSA = Haycock
                       mean    SD
  Annulus (ANN)        1.48   0.14
  Sinuses (ROOT)       2.06   0.18
  STJ                  1.69   0.16
  Ascending aorta      1.79   0.18
Detroit [unverified]: Z = (ln D[cm] − (b0 + b1 BSA + b2 BSA² + b3 BSA³)) / √MSE,  BSA = DuBois
  Annulus   −0.874  2.708  −1.841  0.452   MSE 0.010
  Sinuses   −0.500  2.537  −1.707  0.420   MSE 0.012
  STJ       −0.759  2.643  −1.797  0.442   MSE 0.018

PHN coefficients are verbatim from Lopez 2017 Table 2 (PMC5812349); α is 0.50 for all four sites. The tests match ParameterZ’s PHN calculator to 10⁻⁶ for three patients. PHN population: healthy, non-obese, term children aged 18 years or younger. Detroit coefficients were reconstructed from ParameterZ’s Pettersen calculator because the paper’s table could not be retrieved, so they are [unverified]; see the Echo Z-Scores page for details. Detroit is not shown above BSA 2.0 m² and has no ascending aorta equation.

Revised Ghent nosology (Loeys 2010)

The journal full text was not retrievable. The rules below follow The Marfan Foundation’s transcription (marfan.org/dx/rules), checked against GeneReviews (Dietz, NBK1335).

• Without family history: (1) aortic root Z ≥ 2 and ectopia lentis; (2) Z ≥ 2 and a bona fide FBN1 variant; (3) Z ≥ 2 and systemic score ≥ 7*; (4) ectopia lentis and an FBN1 variant previously associated with aortic root dilatation.
• With family history (relative diagnosed by the above): (5) ectopia lentis; (6) systemic score ≥ 7*; (7) aortic root Z ≥ 2 at 20 years or older, ≥ 3 under 20*. This page treats exactly 20 years as “20 or older”.
• *Only without discriminating features of Shprintzen-Goldberg, Loeys-Dietz or vascular Ehlers-Danlos syndrome, and after TGFBR1/2, SMAD3, TGFB2, TGFB3, collagen biochemistry or COL3A1 testing when indicated.
• Under 20 years (GeneReviews): “nonspecific connective tissue disorder” when the systemic score is below 7 and/or the aortic root Z is borderline (below 3) without an FBN1 variant; “potential Marfan syndrome” for a sporadic case with an FBN1 variant not previously associated with aortic enlargement and an aortic root Z below 3.

Systemic score (maximum 20; ≥ 7 is positive): wrist AND thumb sign 3 (wrist OR thumb 1); pectus carinatum 2 (pectus excavatum or chest asymmetry 1); hindfoot deformity 2 (plain flat foot 1); pneumothorax 2; dural ectasia 2; protrusio acetabuli 2; reduced US/LS with increased arm span/height and no severe scoliosis 1; scoliosis or thoracolumbar kyphosis 1; reduced elbow extension 1; 3 of 5 facial features 1; skin striae 1; myopia above 3 diopters 1; mitral valve prolapse 1. Items and points match both the Marfan Foundation and GeneReviews lists.

Loeys 2010 calls for an aortic root Z “standardized to age and body size”. The nomogram behind the original thresholds was not verified for this page, and using PHN Z here is an assumption. The page lists which rules the entries satisfy; it does not make a diagnosis, and the alternative diagnoses (ectopia lentis syndrome, MASS phenotype, MVP syndrome, Loeys-Dietz and others) need clinical and genetic evaluation.

References

• Lopez L, Colan S, Stylianou M, et al. Circ Cardiovasc Imaging 2017;10(11):e006979. doi:10.1161/CIRCIMAGING.117.006979
• Pettersen MD, Du W, Skeens ME, Humes RA. J Am Soc Echocardiogr 2008;21(8):922-934. doi:10.1016/j.echo.2008.02.006
• Lopez L, et al. Pediatric Heart Network echocardiographic Z scores: comparison to other published models. J Am Soc Echocardiogr 2021;34(2):185-192. doi:10.1016/j.echo.2020.09.019
• Loeys BL, Dietz HC, Braverman AC, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet 2010;47(7):476-485. doi:10.1136/jmg.2009.072785
• Dietz H. FBN1-related Marfan syndrome. GeneReviews (NCBI Bookshelf NBK1335). ncbi.nlm.nih.gov/books/NBK1335
• Haycock GB, Schwartz GJ, Wisotsky DH. J Pediatr 1978;93(1):62-66. doi:10.1016/S0022-3476(78)80601-5