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Myxomatous degeneration of cardiac valves in a fetus with 6q25.1 (TAB2) deletion

Published online by Cambridge University Press:  03 January 2024

Balaganesh Karmegaraj Open the ORCID record for Balaganesh Karmegaraj [Opens in a new window]
Balaganesh Karmegaraj*
Affiliation:
Sowmi Fetal heart centre, Tirunelveli, TN, India Fetal cardiology Division, Department of Paediatric Cardiology, Amrita institute of Medical Sciences and research centre, Kochi, KL, India
*
Corresponding author: Balaganesh Karmegaraj; Email: [email protected]
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Abstract

Myxomatous degeneration of one or more cardiac valves has been reported in trisomy 18, Noonan, Marfan, and Ehlers-Danlos syndromes. 6q25.1 (TAB2) deletion is one of the notable causes for myxomatous degeneration of cardiac valves. Whole exome sequencing must be considered in these subsets of cases for effective prenatal counselling. A 23-week fetus presented with cardiomegaly, redundant myxomatous tricuspid, mitral valve leaflets, thickened pulmonary valve, and bicuspid aortic valves detected to have 6q25.1 (TAB2) deletion was presented with literature review.

Keywords

Fetusmyxomatous degeneration of cardiac valves6q25.1 (TAB2) deletion
Type
Brief Report
Information
Cardiology in the Young , Volume 34 , Issue 2 , February 2024 , pp. 459 - 461
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Copyright
© The Author(s), 2024. Published by Cambridge University Press

TGF-beta-activated kinase 1/MAP3K7-binding protein 2 (TAB 2 gene) deletion cause cardiac, especially valvular abnormalities and extracardiac abnormalities (distinctive facial features hypotonia, growth abnormalities, developmental delay, and connective tissue abnormalities). The described facial features include frontal bossing, dental problems, ptosis narrow palpebral fissures, and hypertelorism. Reference Thienpont1–Reference Woods, Marson and Coci5 To best of my knowledge, only couple of cases in fetal literature has been reported so far. Reference Weiss, Applegate, Wang and Batista2,Reference Gao and Li9

Case report

A 23-year-old primigravida was referred at 23 weeks gestation for fetal cardiac evaluation in view of cardiomegaly in routine obstetric scan. Four-chamber view showed cardiomegaly with thickened redundant myxomatous tricuspid and mitral valve leaflets. There was significant mitral and tricuspid valve prolapse with moderate tricuspid and mitral valve regurgitation. (Fig. 1a, b; Videoclip 1 and 2) Three-vessel view showed thickened right pulmonary artery. (Fig. 1c) Right ventricular outflow tract view showed thickened pulmonary valve (Fig. 1d, e) and bicuspid aortic valves (fusion of left and non-coronary leaflets) (Fig. 1f). High short-axis basal view of heart during diastole (Fig. 1g) and systole (Fig. 1h; Videoclip 3) showed densely thickened myxomatous tricuspid (arrow) and mitral valve leaflets (bold arrow). Invasive tests ruled out karyotype and 22q11 abnormalities. Whole exome sequencing detected a 471.5-kb deletion in the chromosome 6q25.1 (TAB2 gene). Considering the overall long-term outcome, the parents opted for termination of pregnancy. Parental whole exome sequencing and fetal autopsy were denied.

Figure 1. a – Grey scale 4-chamber view showing cardiomegaly with densely thickened redundant myxomatous tricuspid (arrows) and mitral valve leaflets (bold arrows). b – Four-chamber view colour Doppler showing moderate tricuspid (arrow) and mitral valve (bold arrow) regurgitation. c – Three-vessel view showing thickened right pulmonary artery. Right ventricular outflow tract view showing ( d & e ) thickened pulmonary (red arrow) and ( f ) bicuspid aortic valves (fusion of left and non-coronary leaflets) (red arrow). High short-axis basal view of heart during diastole ( g ) and systole ( h ) showing thickened redundant myxomatous tricuspid (arrow) and mitral valve leaflets (bold arrow).

Discussion

The gene TAB2 [TGF-beta-activated kinase 1/MAP3K7-binding protein 2] mediates the activation of TAK1 in the IL-1 signal transduction pathway. TAB2 haploinsufficiency was associated with CHD. Reference Thienpont1 Up-regulation of TGF-β expression is thought to have a role in mitral valve degeneration. Variable degrees of heart defects involving the valves, outflow tract, and septum have been reported in the literature. Polyvalvular dysplasia has been reported frequently in 6q25.1 (TAB2) deletion apart from trisomy 18, Noonan, Marfan, and Ehlers-Danlos syndromes. Reference Weiss, Applegate, Wang and Batista2 A detailed literature search of various cardiac and extracardiac features of 6q25.1 (TAB2) deletion has been presented in Table 1. Reference Weiss, Applegate, Wang and Batista2-Reference Gao and Li9

Table 1. Summary of previously published reports of 6q25.1 (TAB2) microdeletion syndrome.

Conclusion

6q25.1 (TAB2) deletion is one of the notable causes for myxomatous degeneration of cardiac valves. Whole exome sequencing must be considered in these subsets of cases for effective prenatal counselling.

Supplementary material

The supplementary material for this article can be found at https://doi.org/10.1017/S1047951123004419.

Data availability statement

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Financial support

This research received no specific grant from any funding agency, commercial, or not-for-profit sectors.

Competing interests

None.

Informed consent

Informed consent was obtained as per our hospital policy.

References

Thienpont, B, Zhang L, Postma AV, et al. Haploinsufficiency of TAB2 causes congenital heart defects in humans. Am J Hum Genet 2010; 86: 839–849. DOI: 10.1016/j.ajhg.2010.04.011 CrossRefGoogle Scholar
Weiss, K, Applegate, C, Wang, T, Batista, DA. Familial TAB2 microdeletion and congenital heart defects including unusual valve dysplasia and tetralogy of fallot. Am J Med Genet A 2015; 167A: 2702–2706. DOI: 10.1002/ajmg.a.37210.CrossRefGoogle ScholarPubMed
Cheng, A, Dinulos, MBP, Neufeld-Kaiser, W, et al. 6q25.1 (TAB2) microdeletion syndrome: congenital heart defects and cardiomyopathy. Am J Med Genet A 2017; 173: 1848–1857. DOI: 10.1002/ajmg.a.38254.CrossRefGoogle ScholarPubMed
Cheng, A, Neufeld-Kaiser, W, Byers, PH, Liu, YJ. 6q25.1 (TAB2) microdeletion is a risk factor for hypoplastic left heart: a case report that expands the phenotype. BMC Cardiovasc Disord 2020; 20: 137. DOI: 10.1186/s12872-020-01404-5.CrossRefGoogle ScholarPubMed
Woods, E, Marson, I, Coci, E, et al. Expanding the phenotype of TAB2 variants and literature review. Am J Med Genet A 2022; 188: 3331–3342. DOI: 10.1002/ajmg.a.62949.CrossRefGoogle ScholarPubMed
Engwerda, A, Leenders, EKSM, Frentz, B, et al. TAB2 deletions and variants cause a highly recognisable syndrome with mitral valve disease, cardiomyopathy, short stature and hypermobility. Eur J Hum Genet 2021; 29: 1669–1676. DOI: 10.1038/s41431-021-00948-0.CrossRefGoogle Scholar
Deng, Q, Wang, X, Gao, J, et al. Growth restriction and congenital heart disease caused by a novel TAB2mutation: a case report. Exp Ther Med 2023; 25: 258. DOI: 10.3892/etm.2023.11957.CrossRefGoogle ScholarPubMed
Salpietro, V, Ruggieri, M, Mankad, K, et al. A de novo 0.63 Mb 6q25.1 deletion associated with growth failure, congenital heart defect, underdeveloped cerebellar vermis, abnormal cutaneous elasticity and joint laxity. Am J Med Genet A 2015; 167A: 2042–2051. DOI: 10.1002/ajmg.a.37118.CrossRefGoogle Scholar
Gao, WJ, Li, XN. Prenatal ultrasound diagnosis of primary myxomatous degeneration of cardiac valves in a fetus: case report. J Obstet Gynaecol Res 2022; 48: 2620–2623. DOI: 10.1111/jog.15331.CrossRefGoogle Scholar
Figure 0

Figure 1. a – Grey scale 4-chamber view showing cardiomegaly with densely thickened redundant myxomatous tricuspid (arrows) and mitral valve leaflets (bold arrows). b – Four-chamber view colour Doppler showing moderate tricuspid (arrow) and mitral valve (bold arrow) regurgitation. c – Three-vessel view showing thickened right pulmonary artery. Right ventricular outflow tract view showing (d&e) thickened pulmonary (red arrow) and (f) bicuspid aortic valves (fusion of left and non-coronary leaflets) (red arrow). High short-axis basal view of heart during diastole (g) and systole (h) showing thickened redundant myxomatous tricuspid (arrow) and mitral valve leaflets (bold arrow).

Figure 1

Table 1. Summary of previously published reports of 6q25.1 (TAB2) microdeletion syndrome.

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