- Tuberous sclerosis complex (TSC) is rare genetic disorder mainly characterized by the progressive development of internal growths and tumors in body organs.
- Although a majority of reported TSC cases begin in the brain, growths may also manifest on the skin, eyes, kidneys and vital organs such as the heart and lungs.
- Today, the Centers for Disease Control and Prevention (CDC) reports that empirical statistical data on the exact number of individuals with TSC in the United States alone still remains unknown due to its rarity. However, current estimates of confirmed cases stand at 40,000 (National Organization for Rare Disorders, 2020).
Tuberous sclerosis complex is a debilitating disorder affecting cellular differentiation and migration during the formative stages of development. As a consequence, numerous hamartomatopus lesions develop across different sites in the body and are now characteristically known to affect every organ system (Kirollos et al., 2019). Adomasabaceum is the best-known display of the condition and usually remains dormant; only becoming apparent between late child hood and early adolescence (Ehninger & Silva, 2013). Furthermore, TSC causes the development of scarlet muscular lesions as a common early sign among patients, and often mistaken for acne or freckles.
Pathophysiology Of Tuberous Sclerosis Complex
- Tuberous sclerosis complex is primarily caused by a genetic defect of the TSC1 or TSC2 genes (National Organization for Rare Disorders, 2020).
- As an autosomal dominant disorder, TSC first affects the brain and commonly associated with the development epileptic seizures.
- TSC is also concomitant with focal developmental malformations within the cerebral cortex region of the brain among persons with the condition.
- The development of tubers then follows, and normally recognized by a sudden permeation of giant cells, astrocytes, and dysmorphic neurons (Kwiatkowski et al., 2017).
- Understated neuropathologic variations within the brain may also be present.
Tuberous sclerosis complex is an autosomal dominant disorder primarily caused by prominent inherited defects within the TSC1 or TSC2 genes (Lhatoo et al., 2019). It initially starts in the brain, but later spreads to all organ systems; affecting the eyes, skin, lungs, kidneys, and heart. Developmental malformations, in the form of tubers, then advance in the cerebral cortex, and are commonly discernable by the proliferation giant cells, astrocytes, and dysmorphic neurons. The resulting unregulated cell growth causes spontaneous seizures as a direct consequence of changes in cortical lamination.
Major Defining Features
- Periungual fibroma.
- Hypomelanotic macules.
- Connective tissue nevus.
- Multiple retinal nodular hamartoma.
- Cortical tuber.
- Subependymal nodule.
- Subependymal giant cell astrocytoma.
- Renal AML.
A primary defining feature of Tuberous sclerosis complex is the presence of forehead plaque typically accompanied by Periungual fibroma. Furthermore, the presence of a nontraumatic ungula and shagreen patch also signify the preliminary development of multiple retinal nodular hamartoma, common in most TSC cases. Cerebellar cortical dysplasia, punctuated by the migration of white matter is also one of the early signs of TSC (Ehninger & Silva, 2013). Additionally, the presence of renal AMLs and lymphangioleiomyomatosis (LAM) also signify tuberous sclerosis.
- Abnormal neurological findings.
- Cutaneous manifestations, chief among them being adoma sabaceum.
- Cardiac involvement in the development of rhabdomyomas.
- Ocular abnormalities.
- Cystic pulmonary abnormalities.
- Autosomal dominant polycystic lesions as a consequence of kidney disease.
- Pitting of the dental enamel.
- Hamartomas and polyposis in gastrointestinal area.
- Sclerotic and hypertrophic lesions.
Several clinical manifestations are also associated with the initial advance of TSC. Since the condition is known to originate in the brain, preliminary neurological results usually reveal the proliferation of subependymal giant cell astrocytomas (SEGAs) and subependymal nodules (SENs) (Jones, 2016). Adomasabaceumbegins developing, and becomes apparent during late childhood. TSCs impact during early infancy also results in the development of rhabdomyomas as the most common indication of cardiac disease. The pitting of the teeth is rare in children, but common among TSC patients. Evidence of pitting of the enamel in primary teeth and Sclerotic and hypertrophic lesions on the bones further signify TSC.
- Laboratory studies: Computed Tomography Scanning (CT scans), Renal Ultrasonography, and a routine Echocardiography.
- Assessment tests: Electroencephalography and Electrocardiography.
Tuberous sclerosis complex diagnoses are typically guided by laboratory studies conducted to detect the presence of common genetic alterations associated with the condition. CT scans are performed to detect SEGAs prior to the development of obstructive hydrocephalus play a major role in diagnosis (Learning, 2019). Renal ultrasonography, on the other hand, evaluates variations in cysts, paving the way for operative intervention while a routine echocardiography serves as a major baseline diagnosis test (Kwiatkowski et al., 2017). An electroencephalography is typically conducted as a follow on clinical indications of TSC, while a baseline electrocardiography identifies cardiac arrhythmias in suspected cases.
Treatment And Management
- TSC is a complex medical condition, often requiring specialized care and treatment. The following are some of the most common TSC management practices in use today:
- Pharmacologic treatment: By prescribing antiepileptic medications (AEDs) and medication to manage kidney tumors.
- Surgery: Thermal ablation, stimulation of the vagus nerve, and Corpus callosotomy.
Both surgery and pharmacologic treatment options are recommended in managing TSC. However, the latter is more commonly used today. Antiepileptic medications (AEDs) pharmacologic treatment options for TSC target patient’s epileptic syndrome as a major clinical manifestation of the condition (Jones, 2016, p. 32). Furthermore, kidney medications such as Everolimus (Afinitor) are commonly prescribed to manage lesions and tumors which emerge shortly after affecting the urinary system. Surgical option such as thermal ablation, stimulation of the vagus nerve, and Corpus callosotomy may also be employed.
- Treatment for TSC starts with AEDs to manage epileptic seizures evident among patients.
- The worsening of seizures normally results in inpatient care for TSC patients.
- Inpatient care may also be recommended for patients presenting with retroperitoneal hemorrhage, and pneumothorax or dyspnea as a consequence of TSC-related LAM.
The initial treatment for Tuberous sclerosis complex does not typically require hospitalization and only involves prescribing AEDs to manage epileptic features. However, a further worsening of the condition may result in inpatient care to allow the patient to adjust to AEDs. Cases of hematurias may also cause embolization and a primary reason why evidence of AML and LAM normally results in hospitalization for supportive care.