Prenatal Diagnosis of Cardiac Rhabdomyoma and Cortical Tubers Proven as Tuberous Sclerosis Complex

Abstract

We report a case of multiple fetal cardiac rhabdomyomas and cortical based echogenic masses in a primigravida, detected at 27 weeks of gestation. Prenatal genetic testing revealed a heterozygous 23 base pair deletion of the TSC2 gene. Postnatally, the child presented with seizures and showed multiple bilateral periventricular and subependymal hamartomas with cortical and subcortical tubers on magnetic resonance imaging (MRI). Multiple hypomelanotic macules were seen on the back, chest, and eyelids. Rhabdomyomas are the most common prenatally detected cardiac tumor. They appear as a homogeneous echogenic mass on ultrasound and usually are asymptomatic. In 10% of cases, they can cause complications such as outflow tract obstruction, hydrops, arrhythmia, cardiac failure, and intrauterine death. There is a strong association between cardiac rhabdomyoma and tuberous sclerosis, which has an autosomal dominant inheritance pattern and multisystem involvement. Detection of rhabdomyoma should prompt further evaluation to look for other systemic associations by fetal MRI. Genetic counseling and prenatal testing are advised to confirm the diagnosis, to improve the management of other related symptoms, and to plan future pregnancies.

 

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Keywords

cardiac neoplasm - cortical tubers - fetal ultrasound - heart - prenatal diagnosis - rhabdomyoma - tuberous sclerosis complex

Introduction

Cardiac rhabdomyoma is the most common prenatally detected cardiac tumor and accounts for 50 to 60% of cardiac neoplasms. It is a benign mass and is usually multiple. They are mostly asymptomatic despite being large and multiple. However, they are unpredictable and can present with complications such as hydrops, arrhythmia, and effusions. They are the first findings toward the diagnosis of tuberous sclerosis complex (TSC). Cardiac rhabdomyoma is one of the major criteria for TSC diagnosis. TSC is a rare autosomal dominant neurocutaneous multisystem disorder and presents with hamartomas in the heart, brain, kidneys, and eyes. Early detection helps with conscious decision making by the parents as well as early and appropriate treatment for the infants.

 

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Case Report

A 20 year old primigravida mother with second degree consanguineous marriage came to our fetal care center at 27 weeks for a late anomaly scan. The cardiac evaluation showed three to four homogeneous echogenic masses involving the interventricular septum ([Figs. 1] and [2]) and free walls of both ventricles in four chamber views ([Fig. 3]), the largest measuring 10 × 10 mm. Three vessel view, three vessel and trachea view, left ventricular outflow tract (LVOT) view, and right ventricular outflow tract view were normal with no evidence of outflow tract obstruction. Color Doppler and cardiac velocimetry were within normal limits. No arrhythmia and good ventricular contractility were seen. Head circumference was at the 90th centile and biparietal diameter at the > 99th centile for gestation age. As the fetus was in cephalic presentation, transvaginal sonography (TVS) was done to assess the intracranial structures. TVS showed multiple cortical based echogenic masses in both cerebral hemispheres ([Fig. 4]). The presence of the above two findings raised the suspicion for TSC. A suspicious echogenic focus was noted in the fetal right kidney, likely an angiomyolipoma. The maternal kidneys were evaluated and appeared normal. There was no significant family history of seizures, skin lesions, or genetic disorders.

Fig. 1 Axial ultrasound image at the level of four chamber view showing two homogeneous echogenic masses seen in the right and left ventricles engulfing the interventricular septum.

Fig. 2 Ultrasound image of right ventricular outflow tract view showing thickened and echogenic interventricular septum along its entire extent.

Fig. 3 Axial ultrasound image at four chamber view showing a few nodular echogenic masses arising from the right and left ventricular free walls.

Fig. 4 Ultrasound image of the parasagittal view of fetal brain showing multiple oval shaped echogenic cortical masses in parieto occipital lobe.

The above findings were explained in detail to the couple, and the high chance of genetic association with TSC was explained. Amniocentesis was performed at a higher center and was sent for clinical exome sequencing. Clinical exome sequencing showed a heterozygous 23 base pair deletion in exon 19 of the TSC2 gene that results in a frameshift and premature truncation of the protein 25 amino acids downstream of codon 670. Parents opted to continue the pregnancy due to advanced gestation at the time of diagnosis and delivered a healthy male at 38 weeks of pregnancy with a birth weight of 3.0 kg. Postnatal transthoracic echocardiogram revealed moderate left ventricular hypertrophy, mildly dilated left atrium, and ventricle with no obvious echogenic masses. Ultrasound of the abdomen was normal. The child presented with ∼8 to 10 gray hypomelanotic shaped macules on the back, eyelids, and chest ([Fig. 5]). The child also presented initially with clenching of hands and up rolling of eyes, which progressed to tonic clonic seizures. Magnetic resonance imaging (MRI) of the brain showed multiple T2 hypointense and T1 isointense bilateral periventricular nodular subependymal hamartomas with cortical and subcortical tubers predominantly in bilateral temporal lobes ([Fig. 6]). Parental full gene sequencing genetic testing was advised for the management of future pregnancies which showed an absent pathogenic variant for the TSC2 gene.

Fig. 5 Two hypopigmented macules to patches present over trunk indicating ash leaf macules.

Fig. 6 Magnetic resonance images: (A) T1-weighted axial image of the brain shows nodular lateral ventricular wall appearance due to isointense subependymal nodules. (B) T2-weighted coronal image shows a hypointense subcortical tuber in the right parietal lobe. (C) T2-weighted coronal image at the level of lateral ventricular atria shows nodular T2 hypointense subependymal hamartomas.

 

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Discussion

Primary cardiac tumors are a rare prenatal finding. Rhabdomyoma is the most common prenatally detected cardiac tumor, accounting for 60 to 70% of cardiac tumors.[1] Incidence of rhabdomyoma is reported as 0.17% in prenatal fetal life.[2] They are usually multiple rather than single. The most common locations involved are the left ventricle and the interventricular septum. Incidence in the subepicardial region and atria is low.[3] Even in the presence of multiple rhabdomyomas, they can be asymptomatic. However, in 10% of the cases, outflow tract obstruction may occur leading to cardiac failure, hydrops, and intrauterine death.[2] Twenty three percent of the children may present with arrhythmia,[4] which occurs due to abnormal conduction and electrical excitement in the tumor at the level of the atrioventricular junction. The size of the tumor increases gradually peaking at the second to third trimester and gradually reduces in size near term and after birth in more than half of the cases.[5] The size of the tumor decreases due to a fall in maternal estrogen levels.[6] Therefore, surgical intervention is deferred unless the tumor causes significant outflow tract obstruction or arrhythmia.

On ultrasound, rhabdomyoma appears as a homogeneous echogenic lesion. Major risk factors that can impact the outcome are number, size, location, progression, and other associated abnormalities or malformations.[7] However, prenatal MRI may be beneficial to demonstrate the presence of cerebral and renal lesions better.

A major concern of rhabdomyoma is its association with TSC in 50 to 80% of the cases and is usually the first manifestation that can be detected antenatally.[8] TSC is a multisystemic autosomal dominant disease that manifests with the growth of benign hamartomas in various organ systems.[9] It occurs due to a mutation in tumor suppressor genes TSC1 on chr9q34 (coding for hamartin) and TSC2 on chr16p13.3 (coding for tuberin). These genes are mostly seen in neural, retinal, epithelial, renal, and cardiac cells.[7]

Prenatal MRI can demonstrate cortical subcortical tubers and subependymal nodules. These are benign lesions but can trigger seizures by acting as an epileptic focus. They appear T1 isointense and T2 isointense to mildly hyperintense.[9] The number and location of cortical tubers correlate with the risk of epilepsy and neurodevelopmental outcomes in children with TSC. Ultrasound is not sensitive enough to evaluate cerebral lesions, except for large subependymal tumors and cannot easily differentiate subependymal nodules from subependymal hemorrhage.[10]

Detection of rhabdomyoma should warrant genetic counseling to detect TSC mutation in at risk families by either chorionic villous sampling or amniocentesis. Genetic test suggested when suspecting TSC is next generation sequencing (NGS), which identifies pathogenic variants in TSC1/TSC2. If large deletions or duplications are detected on NGS, multiplex ligation dependent probe amplification (MLPA) is done for confirmation. Whole exome sequencing can be suggested if NGS and MLPA are normal, to look for other pathogenic genes that can present with TS-like manifestation. Parental exome sequencing is also advised to know if it is a dominant or a de novo mutation.[11] Treatment options with mTOR inhibitors such as sirolimus and everolimus have been tried and shown promising results in a reduction of the size of the tumor, especially in symptomatic patients presenting with LVOT obstruction, heart failure, or large rhabdomyomas as an alternative to surgical treatment.[8]

 

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Conclusion

Rhabdomyoma is a benign hamartoma that has a strong association with TSC. It is the earliest predictor for TSC. Ultrasound should be complemented with prenatal MRI to assess the multisystemic involvement. Most of the rhabdomyomas are asymptomatic. However, follow up is needed to monitor their progression and the development of complications. Genetic counseling and invasive testing are recommended to help with decision making and early management of affected fetuses requiring prompt treatment.

 

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Conflict of Interest

None declared.

Note

Work attributed to: Konnect Fetal medicine and Diagnostic center, Boduppal, Hyderabad.

Consent for Publication

Informed consent was obtained from the patient prior to the study.

Grants and Support

None.

• References

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Publication History

Article published online:
22 July 2025