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https://doi.org/10.15836/ccar2021.188

Aortic dilatation and miscarriages as a main presentation of FLNA mutation in a Croatian family: a case report

Marija Tomac Stojmenović orcid id orcid.org/0000-0003-4257-0178 ; Psychiatric Hospital Rab, Rab
Vlatka Rešković Lukšić orcid id orcid.org/0000-0002-4721-3236 ; University of Zagreb School of Medicine
Irena Ivanac Vranešić orcid id orcid.org/0000-0002-6910-9720 ; University of Zagreb School of Medicine
Velena Radošević ; University of Zagreb School of Medicine
Tamara Žigman ; University of Zagreb School of Medicine
Maja Hrabak Paar orcid id orcid.org/0000-0002-0390-8466 ; University of Zagreb School of Medicine
Jadranka Šeparović Hanževački orcid id orcid.org/0000-0002-3437-6407 ; University of Zagreb School of Medicine


Puni tekst: engleski pdf 430 Kb

str. 188-188

preuzimanja: 327

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Sažetak

Ključne riječi

FLNA mutation; miscarriage; aortic dilatation; aortic dissection

Hrčak ID:

257032

URI

https://hrcak.srce.hr/257032

Datum izdavanja:

4.5.2021.

Posjeta: 856 *



Introduction: The FLNA gene provides instructions for producing protein filamin A. It is found on the X chromosome and has X linked inheritance. The dysfunction of this gene is associated with congenital malformation of the cerebral cortex, cardiac abnormalities, thoracic aneurism and joint hypermobility. (1-4)

Case report: We present a family with heterozygous pathogenic variant of FLNA. Disease was discovered during workup of older daughter’s miscarriages. She had a double miscarriage in the first trimester. She knew for mild mitral and aortic regurgitation from youth. From family history: mother had two miscarriages and two successful deliveries, pulmonary hypertension, coronary artery disease and percutaneous coronary intervention at the age of 56, grandmother from mother side had one successful delivery and three miscarriages, died at the age of 64 from diabetic coma. Sister has moderate aortic regurgitation, dilatation of ascending aorta (42mm), one miscarriage. Father has dilatation of ascending aorta. In 2020. echocardiography revealed dilatation of the ascending aorta (43mm) with mild central aortic regurgitation, and a trace of mitral regurgitation. The cardiologist recommended CT aortography and genetic testing. On CT aortography aorta was measured at a maximum of 46mm (Figure 1). Genetic testing identified one pathogenic variant in FLNA. After this discovery, genetic testing was performed on all family members (Figure 2), and mutation was identified in the mother and sister. During this workup, the younger sister found out that she was pregnant. Soon, the mother suddenly died at the age of 60. Autopsy revealed a dissection of the thoracic aorta. With this finding, the younger sister went from category three to category four in classification of maternal cardiovascular risk score and was advised to abort. At the time of writing this paper she is 10 weeks pregnant and, knowing all the risks, does not want an abortion.

FIGURE 1 CT scan, dilatation of the ascending aorta.
CC202116_5-6_188-f1
FIGURE 2 Genetic tree.
CC202116_5-6_188-f2

Conclusion: In young women with dilatation of ascending aorta, connective tissue disease should be considered. Today we have possibility for family screening, so we can discover pathogenic mutation in families. In FLNA mutation, safe size of ascending aorta dilatation is smaller than in healthy population, which should be considered during pregnancy planning. In case of pregnancy multidisciplinary approach is mandatory.

LITERATURE

1 

Chin JM, Bartholomew ML. Aortic aneurysm and dissection in pregnancy: A case report. Case Rep Womens Health. 2020 October 2;28:e00261. https://doi.org/10.1016/j.crwh.2020.e00261 PubMed: http://www.ncbi.nlm.nih.gov/pubmed/33083238

2 

Reinstein E, Frentz S, Morgan T, García-Miñaúr S, Leventer RJ, McGillivray G, et al. Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in Filamin A. Eur J Hum Genet. 2013 May;21(5):494–502. https://doi.org/10.1038/ejhg.2012.209 PubMed: http://www.ncbi.nlm.nih.gov/pubmed/23032111

3 

Clarke CM, Fok VT, Gustafson JA, Smyth MD, Timms AE, Frazar CD, et al. Single suture craniosynostosis: Identification of rare variants in genes associated with syndromic forms. Am J Med Genet A. 2018 February;176(2):290–300. https://doi.org/10.1002/ajmg.a.38540 PubMed: http://www.ncbi.nlm.nih.gov/pubmed/29168297

4 

de Wit MC, de Coo IF, Lequin MH, Halley DJ, Roos-Hesselink JW, Mancini GM. Combined cardiological and neurological abnormalities due to filamin A gene mutation. Clin Res Cardiol. 2011 January;100(1):45–50. https://doi.org/10.1007/s00392-010-0206-y PubMed: http://www.ncbi.nlm.nih.gov/pubmed/20730588


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