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Ventricular outflow obstruction, valve aplasia, bradyarrhythmia, pulmonary hypoplasia and non-immune fetal hydrops because of a large rhabdomyoma in a case of unknown tuberous sclerosis: a prenatal diagnosed cardiac rhabdomyoma with multiple symptoms
Department of Obstetrics and Gynaecology, University of Essen, Germany
Cardiac tumours are very rare in intrauterine life and early infancy. Their prenatal incidence in screening examinations is estimated as 9/100,000 in a mixed group of high and low risk pregnancies but increases to 2/1000 in centres for paediatric cardiology.1,2 The most common type of tumour in this group is rhabdomyoma with about 70–80% of all cardiac tumours in clinical series and about 40% in autopsy series.2–4
Von Recklinghausen was the first to describe a cardiac rhabdomyoma in a stillborn in 1862. Bourneville coined the term ‘tuberous sclerosis’ 18 years later. Especially in early infancy and intrauterine life, cardiac rhabdomyomas are associated with tuberous sclerosis in 50%.5 The incidence of rhabdomyoma in patients with tuberous sclerosis differs from 43% to 72%.3
Several case reports as well as clinical studies have described the appearance of rhabdomyoma in different conditions. We report a case of fetal rhabdomyoma accompanied by a combination of multiple fetal symptoms, which led to a new diagnosis of tuberous sclerosis in the mother.
We present the case of a 19 year old primigravida without any previous history of diseases or pregnancy complications. The fetal cardiac tumour was first noticed during an ultrasound screening at 22 + 2 weeks of gestation. At this time, the fetus showed prolonged episodes of bradycardia and had a pericardial effusion. A MRI suggested a cardiac rhabdomyoma and showed the tumour inside the left ventricular wall with a diameter of 19 mm. We first examined the fetus at 28 + 0 weeks of gestation. Ultrasound showed all signs of fetal hydrops. The rhabdomyoma was 40 × 35 × 32 mm in size and was located inside the left ventricular wall. The size of the heart was 55 × 36 × 35 mm. As you can see in the ultrasound figure attached, the left outflow tract was completely obstructed by the tumour protruding into the left ventricle and the atrium. The mitral valve was fully displaced; the aortic valve appeared to be hypoplastic. The structure of the right ventricle was not affected (see Fig. 1). Both lungs seemed hypoplastic. The heart rate was about 130/minute with a few supraventricular extrasystoles. There was reversed blood flow through the foramen ovale. The ductus arteriosus was prominent and showed a regular blood flow. The ascending aorta as well as the aortic arch showed a reversed flow pattern. Doppler measurements of the descending aorta and the umbilical artery showed a normal pattern. The a-wave of the ductus venosus was positive, however, the pulsatility index was elevated. No venous pulsation was observed. We discussed the findings and the prognosis closely with the parents and the paediatric cardiologists. The parents decided to continue pregnancy but not to have close sonographic surveillance. The fetus died four weeks later at 32 weeks of pregnancy. The autopsy and histological examination confirmed the prenatal diagnosis of the suspected rhabdomyoma protruding into the left outflow tract and atrium. The mitral valve was atretic. Macro- and microscopically, both lungs appeared highly immature. The neuropathological examination revealed a subependymal giant cell astrocytoma.
The 19 year old patient showed multiple typical dermatological symptoms such as Adenoma sebaceum, Koenen-Tumour, Shagreen patch and an ash leaf spot. According to the tuberous sclerosis consensus conference, the disease was confirmed in both the mother and the stillborn.6 However, molecular analysis did not reveal one of the two known genes of tuberous sclerosis.
The tuberous sclerosis complex is an autosomal dominant inherited neurocutaneous syndrome characterised by hamartomatous growth in multiple organs. Two gene defects (hamartin on 9q34.3 and tuberin on 16p13.3) are known to produce the phenotype, although 66% are de novo mutations.7 Therefore, prenatal testing is only available on a limited basis in cases of known disease-related mutations. Additionally, the highly variable expression does not allow the prediction of tuberous sclerosis even in affected children.
The diagnostic criteria for tuberous sclerosis rely mainly on the dermatological and neurological symptoms and signs, such as hypomelanotic macules, lumbosacral angiofibromas or periungual fibromas, seizures, mental disorder and behavioural impairment.
In general, cardiac tumours are diagnosed in the second half of pregnancy. The typical ultrasound examination of rhabdomyomas shows multiple, hyperechogenic, well-defined homogenous masses in the ventricular wall or the interventricular septum. Rhabdomyomas tend to grow until 32–40 weeks of gestation to a variable size of some millimetres up to centimetres.3 They decrease during the first year of life, possibly as a result of hormonal changes after birth.8
Other intracardiac tumours that need to be considered in the differential diagnosis include: fibromas (11–12% of all cardiac tumours), which are usually solitary and are located inside the ventricular wall. They usually show a homogenous echogenity, almost indistinguishable from rhabdomyoma, but in contrast to rhabdomyoma, sometimes show central necrosis with calcification and cystic degeneration.2,9 Fibromas usually do not regress in early infancy.9 Teratomas, which represent 2–25% of all cardiac tumours, appear as extracardiac tumours with mixed echogenity. They can cause serosanguineous pericardial effusion as well as non-immune fetal hydrops and respiratory distress by tumour compression.2,9 Other cardiac tumours are extremely rare.4,9 Myxomas, the most common tumours among adults, have not been reported in intrauterine life yet.
Morbidity and mortality of rhabdomyomas are low. The overwhelming majority of patients are asymptomatic at birth, the tumours remain silent and regress spontaneously without relapse.3 However, if symptoms manifest in intrauterine life and infancy, the prognosis is much worse. Fenoglio et al.10 reported a mortality of 78% in symptomatic children within one year after delivery.
The clinical appearance in the presented case is typical for the variety of manifestations of cardiac rhabdomyoma:
Arrhythmic cardiac disorders. Tachy- and bradyarrhythmia, especially of supraventricular origin, pre-excitation syndromes, particularly Wolff–Parkinson–White syndrome and sudden cardiac arrest are common.3,11 They are caused by local compression of the heart conduction system by the growing tumour, especially on the sinus node and on its providing arteries.12 Additionally, tumour cells, structurally identical to Purkinje cells, can act as atrioventricular junctions and possible accessory conductive pathways.11 Such dysrhythmias can lead to fetal death.
Obstruction. The growing tumour can protrude into the cardiac chambers, displace their valves and even cause a complete in- and outflow obstruction.12 As seen in our case, blood flow was intermittently reversed at the foramen ovale. The right ventricle is able to maintain the systemic circulation through the Ductus Botalli.12 The left outflow obstruction results in reversed blood flow in the ascending aorta and the aortic arch and therefore the arteries of the neck are supplied by the right ventricle. This might cause congestive heart disease.12 Continued blood flow through the foramen ovale is the key to intrauterine survival in this situation. If the growing tumour obstructs the foramen ovale and interrupts the necessary left-to-right shunt, fetal circulation cannot be sustained. This probably happened in our case.
Myocardial hypoperfusion and loss of functional myocardium. The growing tumour can lead to cardiac artery compression with consequent myocardial hypoperfusion and a replacement of functional myocardium. Both factors result in a reduction of contractility and cardiac output.12
Pulmonary hypoplasia. Rhabdomyomas can prevent the normal pulmonary development most probably by an extrinsic compression of the lungs combined with pleural effusion.13,14 A second approach is a possible alteration of the fetal swallowing mechanism caused by central tumour growth in cases of tuberous sclerosis.13,14
The prenatal management of tuberous sclerosis and cardiac rhabdomyoma is difficult. First, the fetal heart has to be examined thoroughly in patients with tuberous sclerosis as rhabdomyomas are generally much smaller than in our case. A prenatally found cardiac rhabdomyoma should lead to closer maternal examinations concerning tuberous sclerosis.
The prognosis of symptomatic rhabdomyomas is poor and the numerous impairing manifestations of tuberous sclerosis have to be considered as well. In these cases, termination of pregnancy is one option which should be clearly discussed. Surgical resection after delivery is reserved only for children with severe blood flow obstruction or life-threatening rhythm disorders,3 as a complete removal of the tumour is difficult.15 Other groups refuse any aggressive intervention and emphasise the conservative approach because of the tumour's tendency to regression after birth.2
The authors would like to thank Dr B. Albrecht (Department of Human Genetics) and Dr S. Y. Sheu (Department of Pathology) for their support and Dr S. Tinschert (Charité University of Berlin) for the diagnosis of tuberous sclerosis.