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.