English Version
L. Carter · I. Ioannou

Tuberous sclerosis complex

Tuberous sclerosis complex

Schlüsselwörter Tuberous sclerosis complex; ICD 10: Q85.1; Synonyms: Tuberous sclerosis, Bourneville disease, Epiloia
Keywords Tuberous sclerosis complex; ICD 10: Q85.1; Synonyms: Tuberous sclerosis, Bourneville disease, Epiloia
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Tuberous sclerosis complex (TSC) is an uncommon, neurocutaneous multisystem genetic disorder. It was classically described as presenting in childhood with a pathognomonic triad (Vogt triad) of seizures (absent in one-quarter of individuals), intellectual disability (up to half have normal intelligence) and sebaceous adenoma (only present in about three-quarters of the patients) [1]. The full triad is only seen in a minority of patients (~ 30 %).

Therefore, diagnostic criteria have been developed to aid the diagnosis of tuberous sclerosis.
There are 2 genetic loci: TSC1, found on chromosome 9q34; and TSC2, found on chromosome 16p13 [2,3,4] coding for the proteins hamartin and tuberin, respectively. These proteins act as tumour growth suppressors, regulating cell proliferation and differentiation. In
TSC patients, TSC1 or TSC2 mutations give rise to hyperactivation of the mTOR pathway, inducing several abnormalities in numerous cell biochemical processes such as cell cycle regulation and control at transcriptional, translational, and metabolic levels [5]. More recently,
mTOR inhibitor drugs, such as everolimus, have been licensed for use in the treatment of specific clinical manifestations of TSC in certain countries, e.g., subependymal giant cell astrocytomas, renal angiomyolipomas, therapy of refractory epilepsy [6] and in patients with
cardiac or pulmonary involvement. Everolimus can take over the function of the proteins hamartin and tuberin, which are missing due to the genetic defect. Approximately one-third of the patients inherit mutations via the autosomal dominant route with the remaining two-thirds of patients born with new sporadic mutations. The TSC2 gene is more common in both the familial and sporadic forms of the condition. The incidence is approximately 1 in 5,000 – 10,000 live births [7]. The condition is characterised by cellular hyperplasia, tissue dysplasia, and multiple organ hamartomas (benign tumours). TSC shows wide phenotypical variability with patients harbouring the TSC2 gene exhibiting the more severe clinical manifestations. The benign tumours seen in TSC can occur in almost all organ systems, e.g., on the skin, brain, kidneys, heart, lungs, liver, spleen, pancreas, gastrointestinal tract, gingivae and the retinas. Clinical symptoms may include epilepsy, which can be refractory, developmental delay, behavioural problems, and autism. Three types of brain tumour are commonly associated with the condition: giant cell astrocytoma, cortical tubers (after which the disease is named) and subependymal nodules. The growths on the kidneys can be angiomyolipomas (AMLs) or renal cysts. Renal AMLs can produce pain and haemorrhage in adulthood, whereas the cysts are more likely to cause damage to the renal parenchyma causing hypertension and chronic kidney disease which is exhibited in < 5 % of patients overall [8,9]. Cardiac rhabdomyomas are single or multiple and can be seen antenatally. If symptomatic, they present in the neonatal period, but this is rare. They tend to regress in childhood without the need for intervention [2,8]. Lymphangioleiomyomatosis (LAM) of the lungs occurs in 40 % of women with TSC and appears to be hormonally sensitive. It can cause recurrent pneumothoraces [10] and in some cases leads to progressive, irreversible cystic cavitations within the lungs. For certain patients, this can ultimately lead to death without lung transplantation. The main anaesthetic concerns in the treatment of patients with TSC are related to cardiorespiratory complications secondary to progressive damage to the lung parenchyma in adults and the potential for arrhythmias, outflow tract obstruction and venous thromboembolic events in children. Consideration must also be given to anaesthetic drug choices in view of possible renal impairment and medications that the patients may have been prescribed to take long term. Oral lesions on the tongue, palate and less commonly the pharynx and larynx may interfere with anaesthetic airway management [11,12]. In addition, practical difficulties may arise when anaesthetising patients with developmental delay and challenging behaviour. Despite ongoing research into TSC, certain aspects related to its diagnosis and treatment remain unexplained, therefore, the anaesthetist is presented with challenges when planning the perioperative management of these patients.