Rhabdomyomas and Tuberous sclerosis complex: our experience in 33 cases

Abstract

BackgroundRhabdomyomas are the most common type of cardiac tumors in children. Anatomically, they can be considered as hamartomas. They are usually randomly diagnosed antenatally or postnatally sometimes presenting in the neonatal period with haemodynamic compromise or severe arrhythmias although most neonatal cases remain asymptomatic. Typically rhabdomyomas are multiple lesions and usually regress spontaneously but are often associated with tuberous sclerosis complex (TSC), an autosomal dominant multisystem disorder caused by mutations in either of the two genes, TSC1 or TSC2. Diagnosis of tuberous sclerosis is usually made on clinical grounds and eventually confirmed by a genetic test by searching for TSC genes mutations.MethodsWe report our experience on 33 cases affected with rhabdomyomas and diagnosed from January 1989 to December 2012, focusing on the cardiac outcome and on association with the signs of tuberous sclerosis complex. We performed echocardiography using initially a Philips Sonos 2500 with a 7,5/5 probe and in the last 4 years a Philips IE33 with a S12-4 probe. We investigated the family history, brain, skin, kidney and retinal lesions, development of seizures, and neuropsychiatric disorders.ResultsAt diagnosis we detected 205 masses, mostly localized in interventricular septum, right ventricle and left ventricle. Only in 4 babies (12%) the presence of a mass caused a significant obstruction. A baby, with an enormous septal rhabdomyoma associated to multiple rhabdomyomas in both right and left ventricular walls died just after birth due to severe heart failure. During follow-up we observed a reduction of rhabdomyomas in terms of both number and size in all 32 surviving patients except in one child. Eight patients (24,2%) had an arrhythmia and in 2 of these cases rhabdomyomas led to Wolf-Parkinson-White Syndrome. For all patients the arrhythmia spontaneously totally disappeared or was reduced gradually. With regarding to association with tuberous sclerosis, we diagnosed tuberous sclerosis clinically in 31 babies (93,9%).ConclusionRhabdobyomas are tumors with favorable prognosis because they frequently do not cause symptoms and they often regress in numbers and size. Nevertheless, due to frequent association with tuberous sclerosis complex and the resulting neurological impairment, the prognosis can result unfavorable.

Causes of mortality in individuals with tuberous sclerosis complex

“…Although not reported from our clinic population, mortality in childhood in TSC may occur secondary to cardiac rhabdomyomas, which are TSC‐related hamartomas that grow in foetal life and can cause a significant problem around the time of birth by such mechanisms as obstruction to blood flow or life‐threatening arrhythmias. The cardiac rhabdomyomas tend to regress in size after the perinatal period and are unlikely to be a cause of death in cases ascertained through a TSC clinic, and this is a factor that would tend to bias downwards estimates of death in childhood in studies such as ours …”

“…The cardiac rhabdomyomas tend to regress in size after the perinatal period and are unlikely to be a cause of death in cases ascertained through a TSC clinic, and this is a factor that would tend to bias downwards estimates of death in childhood in studies such as ours. 16 In the surviving cohort, there was no significant sex imbalance (132 females, 134 males). The mortality in females was higher that of males (10 vs 6) but this difference was not statistically significant (two-tailed Fisher exact test for proportions of females vs males dying, p=0.441).…”

Myocardial Fatty Foci in Adult Patients with Tuberous Sclerosis Complex: Association with Gene Mutation and Multiorgan Involvement

“…They are reported in 47%267% of patients with TSC, but they rarely occur in patients without TSC (1,5). Rhabdomyomas are commonly detected during fetal life or infancy and may be the first sign of TSC; 70% of them regress before the patient reaches 4 years of age (5,6). A prenatal diagnosis of cardiac rhabdomyoma confers a 75%-80% probability for TSC (1).…”

Diagnosis of tuberous sclerosis complex in the fetus

“…Crawford). In the last decades a growing number of case reports have been described in the literature (23,28,(30)(31)(32)(33)(34)(35)(36) along with original case series studies (11,21,24,25,26,22,29) researching the clinical association of cardiac tumors in fetuses with TSC diagnosis. Most studies are small in number and lack long-term follow-up data (22.…”