Prenatal diagnosis and outcomes of fetal cardiac rhabdomyomas: evaluation of seven cases

Introduction

Prenatal diagnosis of cardiac tumors was reported for the first time in 1982 [1]. Since the time imaging technologies, such as MRI and fetal echocardiography, were used the number of reported cases has increased. Reports that shows its coexistence with tuberous sclerosis (TS) are also surfacing [2]. In these cases, alongside the coexistence with TS, their mortality rates have been reported differently in different case series (0–100%) [3]. In our own clinic, we have done prenatal and postnatal evaluation of seven cases of fetal cardiac rhabdomyoma that was diagnosed prenatally. We also showed that these cases stand a chance for medical treatment independent of tumor size and number.

Case presentations

A retrospective study was conducted in Division of Maternal Fetal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey. We reviewed the prenatal sonographic data and postnatal medical records of fetuses diagnosed for fetal cardiac tumor between January 2001 and March 2014. Patient demographics, gestational age at the point of diagnosis (weeks), sonographic findings (tumor localizations, sizes, cardiac functions, the outflow patterns of the heart, the presence of pericardial effusion, and the presence of hydrops fetalis), pregnancy outcome, and pathological findings were also recorded. Postnatal final diagnoses and treatment modalities (medical or surgical) were also recorded. Between January 2001 and March 2014, 49,255 ultrasound scans were performed on pregnant women at various gestational ages in our maternal fetal medicine unit. This study was approved by the institutional ethics review board (reference number: GO 15/310). During this period, we diagnosed seven fetuses with fetal cardiac rhabdomyoma. All the patients were referred to our clinic with the suspicion of a cardiac mass from different centers. The patient demographics and clinical courses of the seven cases with cardiac rhabdomyoma are shown in Table 1. The mean age of the pregnant women was 32.14±4.29 years (range: 27–41 years). The mean gravida of the pregnant women was 1.85±0.69, and of these 28.57% were primiparous. The mean gestational age at the time of initial diagnosis was 32.0±4.86 weeks. Only one case was identified at 23^rd gestational week, whereas the other six were determined at 3^rd trimester. Five cases had multiple tumors (Figure 1) and two cases had single tumor. The mean size of the tumors was 21.00±12.1 mm (range: 7–36 mm). Termination of pregnancy was performed on fetuses due to hydrops fetalis at 23^rd gestational weeks. The underlying factor for fetal hydrops in this case was hemodynamic cardiac decompensation caused by tumor and there was no additional fetal anomaly. Serial sonography follow-up was carried out to all survivor infants. Some therapeutic modalities everolimus (an mTOR inhibitor that can be administered orally, is well tolerated) and etoposide+carboplatin were used at postpartum follow-up period. Propranolol was used for cardiac dysrhythmias and sodium valproate and clobazam were used for prophylaxis of epileptic seizures for infant with TS (case 2). Surgical treatment was performed on two cases whose tumor sizes were slightly larger than other cases (case 5=30 mm and case 7=32 mm). The histopathological diagnoses were obtained from case 5, 6, and 7.

Figure 1:

Sonographic image shows a case with multiple rhabdomyomas (case no=7).

Discussion

Fetal cardiac rhabdomyomas are the most common cardiac tumors at fetal stage which accounted for 60 to 86% primary cardiac tumors, and the frequency in liveborn infants is around 0.08% [3]. The other cardiac tumors such as fibroma, myxoma, teratoma, and hemangioma are also present. Rhabdomyomas are hyperechoic, homogenic masses with clear-cut borders and variable sizes generally located in the ventricular or septal walls [3]. In our series, there is an exceptional case which had an atrial localization. Small intracardiac echogenic foci being the most frequently encountered finding at the early 2^nd trimester, fetal echocardiography must be repeated at the late 2^nd trimester for excluding rhabdomyoma [2]. Large or growing multifocal masses have more importance due to the fact that they strongly support rhabdomyomas.

The earliest tumor ever determined in the intrauterine life was reportedly identified at the 15^th gestational week [4]. Mean diagnosis time in our series was 33^rd gestational week and our finding is consistent with literature [5]. The smallest tumor ever identified and reported is 4 mm [6], the largest is 52 mm [7] as yet. In our series, mean tumor size (mm) was at this range. Increased possibility of fetal death due to >20 mm tumors were not encountered in our series [5].

The diagnostic week of the single hydropic fetus was smaller and the tumor size was slightly larger than the reported average tumor size [5]. None of the identified tumors grew in size in the intrauterine life but rather reduced in size in the postnatal period. Large tumors are strongly associated with hemodynamic disorders, dysrhythmia, and poor outcome [5].

Arrhythmias that continued in the postnatal period could be associated with increased neonatal and infant mortality [5]. In our series, dysrhythmia was present in two fetuses in the intrauterine period; one of these was hydropic and terminated due to poorer prognosis. The other dysrhythmic fetus was diagnosed as TS and started propranolol as medical treatment.

Previous reports described several accompanying structural cardiac malformations such as hypoplastic left heart, Tetralogy of Fallot, and endocardial fibroelastosis [8]. In our series there was no structural cardiac malformations. It is quite difficult to say that the cause of the hemodynamic outcome in the cases with accompanying anomalies is an obstruction in the outflow tracks or a structural anomaly. Some extracardiac malformations (cleft lip and palate, polycystic kidney, and clubfoot, etc.) were reported previously [9]. However, we did not detect additional anomaly in our series. The coexistence of rhabdomyoma and trisomy 21, 13, and 18 has been reported [4]. As the diagnostic week in our series was advanced, karyotyping was not recommended for the patients.

The fetal cardiac rhabdomyomas found in multisystem disease TS case is thought to be caused by a mutation in the tumor suppressor genes TSC1 and TSC2 which are inherited in an autosomal dominant fashion. Even though a normal fetal MRI in the prenatal period guarantees a better postnatal outcome [10], 1 year after birth, a neurologic evaluation including an MRI to eliminate TS is mandatory. Families determined to be at risk of fetal cardiac rhabdomyoma were given information about TS.

If the limitation of small number of patients is ignored, then from our series, the presence of risk factors for TS in a family and the tumors being multifocal or big, appear to be the most important factors affecting neonatal outcomes. Besides, the tumors being big, the presence of hydrops fetalis and fetal dysrhythmia are all indicators of a hemodynamic disorder.