Cardiac–valvular and vascular Ehlers–Danlos syndrome (EDS) have significant cardiovascular issues. The prevalence and significance of such abnormalities in classical (cEDS) or hypermobile EDS (hEDS) remain unclear. We report the prevalence of cardiac abnormalities in patients with cEDS and hEDS.
We identified 532 pediatric patients with potential EDS evaluated at our institution from January 2014 through April 2019 by retrospective chart review. Ninety-five patients (12 cEDS and 83 hEDS patients) met 2017 EDS diagnostic criteria and had an echocardiogram. One patient was excluded due to complex congenital heart disease, and two were excluded due to lack of images. We reviewed echocardiograms for all structural abnormalities.
Of these 95 patients, 1 had mild aortic root dilation, and 1 had mild ascending aorta dilation in the setting of a bicuspid aortic valve. Eleven patients (11.6%) had a cardiac valve abnormality, all of which were trivial to mild. None of the patients required cardiac intervention.
Our results demonstrate that aortic dilation and valvular anomalies are uncommon in cEDS or hEDS patients. Given the lack of evidence, we do not recommend echocardiographic evaluation and surveillance in patients with cEDS and hEDS in the absence of clinical findings or positive family history.
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Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers–Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175:8–26.
McKusick VA. The Ehlers–Danlos syndrome. Heritable disorders of connective tissue. 4th ed. St. Louis: CV Mosby; 1972. p. 292–371.
Beighton P, de Paepe A, Danks D, et al. International nosology of heritable disorders of connective tissue, Berlin, 1986. Am J Med Genet. 1988;29:581–594.
Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers–Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers–Danlos National Foundation (USA) and Ehlers–Danlos Support Group (UK). Am J Med Genet. 1998;77:31–37.
Cabeen WR Jr, Reza MJ, Kovick RB, Stern MS. Mitral valve prolapse and conduction defects in Ehlers–Danlos syndrome. Arch Intern Med. 1977;137:1227–1231.
Leier CV, Call TD, Fulkerson PK, Wooley CF. The spectrum of cardiac defects in the Ehlers–Danlos syndrome, types I and III. Ann Intern Med. 1980;92 (2 Pt 1):171–178.
Dolan AL, Mishra MB, Chambers JB, Grahame R. Clinical and echocardiographic survey of the Ehlers–Danlos syndrome. Br J Rheumatol. 1997;36:459–462.
McDonnell NB, Gorman BL, Mandel KW, et al. Echocardiographic findings in classical and hypermobile Ehlers–Danlos syndromes. Am J Med Genet A. 2006;140:129–136.
Atzinger CL, Meyer RA, Khoury PR, Gao Z, Tinkle BT. Cross-sectional and longitudinal assessment of aortic root dilation and valvular anomalies in hypermobile and classic Ehlers–Danlos syndrome. J Pediatr. 2011;158:826–830.e1.
Wenstrup RJ, Meyer RA, Lyle JS, et al. Prevalence of aortic root dilation in the Ehlers–Danlos syndrome. Genet Med. 2002;4:112–117.
Lopez L, Colan SD, Frommelt PC, et al. Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr. 2010;23:465–495.
Page Children’s Hospital Boston. Z-score calculator. https://zscore.chboston.org. Accessed 27 August 2019.
Ward RM, Marsh JM, Gossett JM, Rettiganti MR, Collins RT 2nd. Impact of bicuspid aortic valve morphology on aortic valve disease and aortic dilation in pediatric patients. Pediatr Cardiol. 2018;39:509–517.
Tiller GE, Cassidy SB, Wensel C, Wenstrup RJ. Aortic root dilatation in Ehlers–Danlos syndrome types I, II and III. A report of five cases. Clin Genet. 1998;53:460–465.
Ritter A, Atzinger C, Hays B, et al. Natural history of aortic root dilation through young adulthood in a hypermobile Ehlers–Danlos syndrome cohort. Am J Med Genet A. 2017;173:1467–1472.
Asher SB, Chen R, Kallish S. Mitral valve prolapse and aortic root dilation in adults with hypermobile Ehlers–Danlos syndrome and related disorders. Am J Med Genet A. 2018;176:1838–1844.
van Karnebeek CD, Naeff MS, Mulder BJ, Hennekam RC, Offringa M. Natural history of cardiovascular manifestations in Marfan syndrome. Arch Dis Child. 2001;84:129–137.
MacCarrick G, Black JH 3rd, Bowdin S, et al. Loeys–Dietz syndrome: a primer for diagnosis and management. Genet Med. 2014;16:576–587.
Zarate YA, Lepard T, Sellars E, et al. Cardiovascular and genitourinary anomalies in patients with duplications within the Williams syndrome critical region: phenotypic expansion and review of the literature. Am J Med Genet A. 2014;164A:1998–2002.
Judge DP, Dietz HC. Marfan’s syndrome. Lancet. 2005;366:1965–1976.
Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 2006;355:788–798.
Yamada K, Watanabe A, Takeshita H, et al. Measurement of serum Tenascin-X in joint hypermobility syndrome patients. Biol Pharm Bull. 2019;42:1596–1599.
Petersen JW, Douglas JY. Tenascin-X, collagen, and Ehlers–Danlos syndrome: tenascin-X gene defects can protect against adverse cardiovascular events. Med Hypotheses. 2013;81:443–447.
Rauser-Foltz KK, Starr LJ, Yetman AT. Utilization of echocardiography in Ehlers–Danlos syndrome. Congenit Heart Dis. 2019;14:864–867.
Freed LA, Levy D, Levine RA, et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med. 1999;341:1–7.
S.L.P. acknowledges funding from the National Heart, Lung, and Blood Institute (K08HL148553).
The authors declare no conflicts of interest.
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Paige, S.L., Lechich, K.M., Tierney, E.S.S. et al. Cardiac involvement in classical or hypermobile Ehlers–Danlos syndrome is uncommon. Genet Med (2020). https://doi.org/10.1038/s41436-020-0856-8
- Ehlers–Danlos syndrome
- connective tissue disorders
- aortic dilation