DOI: https://doi.org/10.21203/rs.3.rs-2011047/v1
Rhabdomyoma are the most common benign cardiac tumors. These are tumors with favorable prognosis because they frequently do not cause symptoms and they often regress in numbers and size. Due to frequent association with tuberous sclerosis complex and the resulting neurological impairment, the prognosis can be unfavorable (1).
Here we report a case of a 7 months old boy who was diagnosed as cardiac rhabdomyoma during fetal life by fetal echocardiography and later went on to develop seizures as a part of tuberous sclerosis complex at 6 months of age. This report also highlights the difficulties in obtaining a diagnosis and practicing the latest evidence based treatment in low income underdeveloped country like nepal especially in patients belonging to the lower socioeconomic class due to financial shortages and lack of resources.
Tuberous sclerosis (also called tuberous sclerosis complex, or TSC) is a rare, multi-system genetic disease. TSC is usually diagnosed in childhood or infancy, and the affected individuals may present with developmental delay, skin manifestations, or seizures. However, it may also be diagnosed earlier or later, based on a wide array of clinical manifestations (2).
After the advent of echocardiography, but before clinical genetic testing was available, studies estimated that up to 70–90% of children with rhabdomyomas have TSC and at least 50% of children with TSC have rhabdomyomas (3).
The Revised Diagnostic Criteria and Surveillance and Management Recommendations From the International Tuberous Sclerosis Consensus Group provide us a guideline for the diagnosis of TSC (Table 1) based on major and minor criterias.
Echocardiography is around 80 percent sensitive for the diagnosis of Rabdomyoma. Its negative predictive value is not known (4).
Genetic testing for mutations in TSC genes is subject to local resources and availability and is not available readily in a poor low income country like Nepal and even if available is not affordable by most patients since the health system here requires patients to pay out of their own pocket.
The patient, 7 months old infant was brought to the opd by his parents with a history of recent onset jerky movements of the left hand followed by lip smacking movements, blinking of eyes and uprolling of eyes since 2 weeks. These attacks were frequent throughout the day, 10–15 episodes throughout the day and each attack lasted for 15–20 seconds duration.
The patient had been diagnosed as rhabdomyoma during fetal life. Fetal echocardiography had shown multiple bright echogenic masses (Fig. 1) at 37 weeks of gestation.
Echocardiography done in neonatal period confimed the masses, as two bright masses in the LV arising from the interventricular septum, one near the apex and other one at the base. The masses were non mobile and did not cause any obstruction to either of the outflow tracts.
So it was decided to observe the child and follow up since the child did not have any arrhythmia either.
Meanwhile the parents lost to follow up and could not afford to do the Cardiac MRI which was adviced.
The parents upon noticing the focal, secondary generalised seizure activity which started 2 weeks back at the age of 6 months, brought the child again for medical attention after the local paramedics could not cure the symptoms.
On examination the child was lethargic. Neurological examination revealed no focal neurological deficits except the plantar reflex which were equivocal. Cardiovascular, Respiratory system examination were unremarkable. On general examination various skin lesions were found. On the groin and back various hypopigmented macules were seen (Fig. 2).
At the nape of the neck and lower back thickened, pigmented and indented patches of skin was found (Fig. 3).
On questioning the mother remembers the skin lesions as being present from birth and has not seeked medical attention for the same.
Echocardiography showed two bright masses in the LV, the larger one near the apex and smaller one near the base. None of the masses were near either outflow tracts and there was no obstruction (Figs. 4 and 5).
So based upon the history, skin findings and imaging reports the patient was sent for consultation with neurologist with a provisional diagnosis of Tuberous Sclerosis Complex and associated Rhabdomyoma.
After the consultation EEG was done which showed spike and wave pattern, MRI Brain was normal. The patient was started on 2 antiepileptic drugs and is now on regular follow up with the neurologist.
This patient is a perfect example of presentation of patients with tuberous sclerosis complex, most of whom can be diagnosed perinatally by fetal echocardiography. Even if the cardiac lesions are non obstructive and cause no mechanical or electrical complications the patient should be screened for and followed up for the development of subsequent multisystem manifestations.
Epilepsy affects 70–90% of patients and is one of the most devastating comorbidities. Typically patients develop seizures at the age between 4 to 6 months and EEG abnormalities predate clinical seizure activity (5). Techniques like Fetal Brain MRI and early EEG monitoring can possibly diagnose the seizure disorder even before it onset (6).
Due to the unavailability of fetal brain MRI and lost to follow up of the patient the seizure could not be diagnosed in our patient, and the patient came to medical attention 2 weeks after seizure onset.
The diagnosis of Rhabdomyoma in fetal life should prompt for further investigations and follow up for Tuberous Sclerosis given the high association in between the two.
Generally all types of seizures are associated with TSC, particularly infantile spasms have been associated with mental retardation and a grim prognosis (7).
Renal lesions represent the second most significant cause of morbidity and mortality in patients with tuberous sclerosis complex (TSC) (8). CKD and renal failure represent a major burden in these patients and are the leading cause of death in adult patients with TSC (9).
In one study out of 40 deaths in TSC patients 10 deaths were due to brain tumours, four patients (who were 40 years of age or older) died of lymphangiomyomatosis of the lung. Thirteen patients with severe mental handicaps died of either status epilepticus or bronchopneumonia. One baby died of cardiac failure due to cardiac rhabdomyomas, and one child died of rupture of an aneurysm of the thoracic aorta (10).
Cardiac lesions in TSC mostly regress after birth. They may compromise ventricular function, interfere with valve movement or result in outflow obstruction, and they are also associated with cardiac arrhythmias (11). In such cases they may require surgical resection.
Skin manifestations are the hallmark of TSC, detected in almost 100% of patients, include hypomelanotic macules (87–100% of individuals, formerly known as ash-leaf spots), facial angiofibromas (47–90%, formerly called adenoma sebaceum), shagreen patches (20–80%), fibrous cephalic plaques (25%), and ungual fibromas (17–87%). Confetti skin lesions (3–58%), dental enamel pits (up to 100% in adults), and intraoral fibromas (20–50%) are described as minor features (11).
Retinal hamartomas are observed in 30–50% of TSC patients, and retinal achromic (hypopigmented) patches in 39%. Unless they involve the macula or optic nerve, ophthalmic lesions are usually asymptomatic (8).
Hepatic angiomyolipomas are described in 10–25% of TSC patients (12).
Details on diagnostic criteria and diagnosis have been provided in the supplementary appendix and also available at www.tsalliance.org/consensus .
TSC is a multisystem disorder and for management a great deal of liaison between multiple sub specialities and departments is needed for patient management.
mTORi have become a very promising treatment option for TSC patients, although their place is yet to be determined as the first-line treatment. Currently, an individualized approach is recommended, and patients treated with mTORi should be followed carefully with particular attention to potential toxicities (8).
The management of seizures in TSC patients is challenging even for the most experienced neurologists and especially in a poor country like Nepal. Lennox-Gastaut syndrome (LGS) is considered an epileptic encephalopathy and is defined by a triad of multiple drug-resistant seizure types, a specific EEG pattern showing bursts of slow spike-wave complexes or generalized paroxysmal fast activity, and intellectual disability. It is frequently associated with tuberous sclerosis complex (13).
This case report highlights the importance of early diagnosis and referral of patients with tuberous sclerosis and also emphasizes the importance of proper history taking and clinical examination which is becoming a dying art nowadays for patient management in our daily busy day to day opd’s and echo room especially in a resource limited setting and a low income country like Nepal where all the latest diagnostic and referral facilities especially genetic and imaging studies might not be readable or be economically feasible.
Acknowledgements
The authors would like to acknowledge the staff and members of the department of cardiology of SGNHC and National Neuro Centre for their support and encouragement.
Author contributions
AM was involved in the study design, its analysis, the writing of manuscript and its editing. LT was involved in the collection of data and editing of manuscript, LT was extensively involved in the final editing of manuscript. The author(s) read and approved the final manuscript.
Funding
The authors of the study received no funding during the duration of the study.
Availability of data and materials
Available on request
Ethics approval and consent to participate
Not applicable
Consent for publication
Not applicable.
Competing interests
The authors of the report declare there is no affiliation with companies that has a financial interest and there is no conflict of interest to declare.
Patient’s consent
Written informed consent for the publication of this case report was obtained from the patient’s parents.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal
relationships that could have appeared to influence the work reported in this paper.
Guidelines
We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. This case report has been prepared in accordance with the 2013 CARE guidelines.