CC Cardiol Croat Cardiologia Croatica Cardiol. Croat. 1848-543X 1848-5448 Croatian Cardiac Society CC 2023 18_5-6_145-6 10.15836/ccar2023.145 Extended Abstract Aortic dilatation and miscarriages as a main presentation of FLNA mutation in a Croatian family – case report, part two https://orcid.org/0000-0003-4257-0178Tomac StojmenovićMarija1* https://orcid.org/0000-0002-4721-3236Rešković LukšićVlatka2 https://orcid.org/0000-0002-6910-9720Ivanac VranešićIrena2 https://orcid.org/0000-0002-0137-8254RadoševićVelena2 https://orcid.org/0000-0003-1184-8798ŽigmanTamara2 https://orcid.org/0000-0002-0390-8466Hrabak PaarMaja2 https://orcid.org/0000-0002-3437-6407Šeparović HanževačkiJadranka2 Insula County Hospital, Rab, Croatia University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia ADDRESS FOR CORRESPONDENCE: Marija Tomac Stojmenović, Županijska specijalna bolnica Insula, Kampor 224, HR-51280 Rab, Croatia. / Phone: +385-51-750-675 / Fax +38551-772-538 / E-mail: marija.tomac.mts@gmail.com 042023 18 5-6 145 146 13032023 29032023 2023 Croatian Cardiac Society KEYWORDS: FLNA mutationpregnancymiscarriageaortic dilatationaortic dissection

Introduction: FLNA gene provides instructions for producing protein filamin A. It plays a role in regulating skeletal and brain development, formation of heart tissue and blood vessels, maintenance of lung tissue, function of digestive system, etc. It is found on the X chromosome and has X linked dominant inheritance (Table 1). Pregnancy with aortic aneurysm is rare but potentially fatal. Aortic dissection in pregnancy accounts for 0,1-0,4% of all dissections. Maternal mortality is high. (1-4) Currently there are no guidelines for the management of vascular, cardiac, and connective tissue problems during pregnancy with FLNA mutation.

Clinical findings in patients with FLNA mutation.
CARDIOVASCULAR CENTRAL NERVOUS SYSTEM GASTROINTESTINAL OTHER
-Aortic dilatation-Outflow tract malformation-Patent ductus arteriosus-Atrial/ventricular septal defect-Vascular malformation -Periventricular nodular hyperplasia-Seizures-Mental retardation-Cerebellar hypoplasia-Early hypotonia-Spasticity-Polymicrogyria -Intestinal malrotation-Congenital short small intestine-Pseudo-obstruction/severe chronicconstipation-Anal stenosis -Joint hypermobility-Thrombocytopenia-Dysmorphic facies-Respiratory infections-Hypospadias

Case report: We present a family (Figure 1) with heterozygous pathogenic variant of FLNA (c.2191-2192insGT (p.Tyr731Cysfs *12)) and aortic aneurism.

Genetic tree.

Mother: double miscarriages (16th week), two deliveries (vaginal), died at age 60, due to aortic dissection. Last known size of ascendent aorta was 43-45mm. She had mild/moderate aortic regurgitation, mild mitral and tricuspid regurgitation, coronary artery disease and underwent percutaneous coronary intervention at the age of 56.

Sister: one miscarriage (8th week), moderate aortic regurgitation, dilatation of ascending aorta (42mm), pulmonary artery dilatation (40mm), mild pulmonary regurgitation, bilateral periventricular heterotopia, hypoplastic body of corpus calosum. In 2021. gave birth (C-section) to a baby girl GA 34+4 weeks. Baby girl is FLNA mutation positive and has subependymal heterotopia, echocardiography is normal.

Sister: double miscarriage (13th, 8th week), mild mitral and aortic regurgitation, aortic dilatation (2020/2022. 46mm/48mm), joint hyperlaxity, hypoplastic back third of corpus callosum, and bilateral periventricular heterotopia. In 2022 she gave birth (C-section) to a healthy boy GA 34+3 weeks (genetic results pending).

Grandmother: one delivery, three miscarriages, died at the age of 64. We don’t have genetic confirmation of mutation. She had sister who has a healthy son, further details are unknown.

Father has dilatation of ascending aorta (41mm), he is not a carrier of FLNA mutation.

Conclusion: Both sisters were advised against pregnancy, because there is still no exact data on this mutation and its influence on aneurism progression and childbirth. The pregnancies were high-risk and required team approach - frequent monitoring by cardiologist and gynecologist (during pregnancy and 6 months after delivery).

Patient consent: Obtained from family.

 LITERATURE FLNA gene: MedlinePlus Genetics [Internet]. [cited 2021 Aug 14]. Available from: https://medlineplus.gov/genetics/gene/flna/ MorisakiTMorisakiH. Genetics of hereditary large vessel diseases. J Hum Genet. 2016 January;61(1):21–6. 10.1038/jhg.2015.11926446364 European Society of Gynecology (ESG); Association for European Paediatric Cardiology (AEPC); German Society for Gender Medicine (DGesGM); Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, Cifkova R, Ferreira R, Foidart JM, et al. ESC Committee for Practice Guidelines. ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J. 2011 December;32(24):3147–97. 10.1093/eurheartj/ehr21821873418 de WitMCde CooIFLequinMHHalleyDJRoos-HesselinkJWManciniGM. Combined cardiological and neurological abnormalities due to filamin A gene mutation. Clin Res Cardiol. 2011 January;100(1):45–50. 10.1007/s00392-010-0206-y20730588