Tuberous Sclerosis

History Taking

Chief Complaint

• Seizures, usually starting in childhood

• Skin abnormalities such as hypopigmented patches or facial angiofibromas

• Mental retardation or developmental delay

History of Presenting Complaint

• Recurrent seizures that could be of varying types (infantile spasms, tonic-clonic, absence seizures etc.)

• Skin abnormalities since birth or early childhood, like ash leaf spots, shagreen patches, facial angiofibromas

• Developmental delay or intellectual disabilities, difficulties in school

• Recent changes or difficulties with vision could indicate retinal hamartomas

• Respiratory symptoms like shortness of breath could indicate lymphangioleiomyomatosis in females or angiomyolipomas in the kidney

• Behavioral changes or psychiatric symptoms like autism spectrum disorder, anxiety, depression, or ADHD

System Review

• Neurological: headaches or other neurological symptoms might suggest subependymal giant cell astrocytomas (SEGA)

• Respiratory: pneumothorax or chylous effusion suggesting lymphangioleiomyomatosis in adult women

• Renal: flank pain, hematuria could suggest renal angiomyolipoma

• Cardiac: arrhythmias or history of sudden death in family could suggest rhabdomyomas

Past Medical History

• Early childhood epilepsy

• History of intellectual disabilities or developmental delay

• History of autism spectrum disorder or other psychiatric conditions

Past Surgical History

• Surgery to remove subependymal giant cell astrocytoma

• Nephrectomy for a complicated angiomyolipoma

• Dermatologic procedures for severe skin manifestations

Drug History

• Antiepileptic drugs for seizure management

• mTOR inhibitors like Sirolimus or Everolimus for SEGA or angiomyolipoma

• Any medications for associated conditions, like ADHD or anxiety

Family History

• Family members with tuberous sclerosis, as the condition is autosomal dominant

• Family history of unexplained seizures or mental retardation

Personal History

• Learning difficulties or special educational needs

• Challenges in employment due to intellectual disabilities or other manifestations of the disease

• Difficulties in social interactions due to associated psychiatric conditions

Social History

• Difficulties in school or work due to cognitive impairment or behavioral problems

• Limitations in daily life activities due to seizures or other manifestations of the disease

• Support systems in place for managing the disease

Travel History

• Not typically relevant in the case of tuberous sclerosis

Vaccine History

• Routine vaccinations; no specific implications related to tuberous sclerosis

OBG History

• Pregnancy complications related to tuberous sclerosis manifestations, such as seizures, renal angiomyolipoma, or lymphangioleiomyomatosis

• Transmission risks to offspring, given the genetic nature of the disease

Physical Examination

General Examination

• Facial angiofibromas or fibrous cephalic plaque on skin examination

• Ash-leaf spots or shagreen patches on skin (using Wood's lamp could enhance visibility)

• Café-au-lait spots

• Ungual fibromas on fingers or toes

Examination of the Hands and Arms

• Hypomelanotic macules or ash-leaf spots may be present

• Shagreen patches could be present on the arms

• Ungual fibromas on the fingers

Examination of the Mouth

• Dental enamel pits

• Fibromas on gingival mucosa

Examination of the Neck

• Typically not directly relevant in tuberous sclerosis

Cardiac Examination

• Murmurs or abnormal heart rhythms could suggest cardiac rhabdomyomas

• Listen for arrhythmias which could be associated with cardiac rhabdomyomas

Respiratory Examination

• Decreased breath sounds, dullness to percussion, decreased vocal resonance if chylothorax present (due to lymphangioleiomyomatosis)

Abdominal Examination

• Flank tenderness or palpable mass could suggest angiomyolipoma of the kidney

• Renal bruits could be heard in large angiomyolipomas

Neurological Examination

• Evidence of developmental delay or intellectual disability

• Signs of increased intracranial pressure (papilledema) could suggest a subependymal giant cell astrocytoma (SEGA)

• Focal neurological signs if patient has history of seizures or if SEGA is present

Additional Examination (If Required)

• Fundoscopic examination may reveal retinal hamartomas

• Skin examination with Wood's lamp to better visualize hypopigmented macules

• Detailed neurologic examination for signs of seizures or other neurologic abnormalities

Investigations

Laboratory Investigations

• Complete Blood Count: to check for anemia or signs of infection

• Kidney function tests: to assess for possible renal impairment due to angiomyolipomas

• Liver function tests: as tuberous sclerosis can affect the liver

• Serum electrolytes: important in patients with seizures, may be altered due to anti-epileptic therapy

• Urinalysis: to check for hematuria (indicator of possible angiomyolipoma)

• Genetic testing: for TSC1 and TSC2 mutations confirmatory for tuberous sclerosis

Imaging Investigations

• MRI Brain: to identify subependymal nodules, subependymal giant cell astrocytomas (SEGAs), and cortical tubers

• CT Chest: to identify lymphangioleiomyomatosis

• Ultrasound or CT abdomen: to detect renal angiomyolipomas and renal cysts

• Echocardiography: to detect cardiac rhabdomyomas, if there is suspicion based on clinical examination

• Eye examination with slit lamp or fundoscopy: for retinal hamartomas

Invasive Investigations

• Skin biopsy: to confirm uncertain cutaneous features

• Renal biopsy: if unsure whether renal mass is angiomyolipoma or another form of renal tumour

• Brain biopsy: rarely, if imaging is not definitive for SEGA

Other Tests

• Electroencephalogram (EEG): to assess seizure type and guide treatment

• Neuropsychological testing: to assess for cognitive impairment

• Pulmonary function tests: if lymphangioleiomyomatosis is suspected, to assess severity and monitor progression

• Developmental assessment: in pediatric cases, for early intervention of developmental delays

Management

General Management

• Patient education: about the nature of the disease, treatment options, genetic implications, and need for regular monitoring

• Multidisciplinary team approach: involving neurology, nephrology, dermatology, pulmonology, psychiatry, and other specialties as required

• Genetic counseling: for patients and their families, given the genetic nature of the disease

Medical Management

• Anti-epileptic drugs: for seizure control, choice depends on seizure type

• mTOR inhibitors (Everolimus or Sirolimus): for subependymal giant cell astrocytomas (SEGA) and renal angiomyolipomas

• Bronchodilators and other symptomatic management: for lymphangioleiomyomatosis

Surgical Management

• Nephron-sparing surgery or embolization: for symptomatic or large renal angiomyolipomas

• Neurosurgery: for removal of SEGAs causing symptoms or hydrocephalus

• Dermatological procedures: for severe cutaneous manifestations

• Lung transplantation: in severe cases of lymphangioleiomyomatosis

Other Management

• Therapies for developmental delay or intellectual disability: such as speech, occupational, and physical therapies

• Psychiatric care: for associated psychiatric disorders

• Regular monitoring: including imaging of the brain, kidneys, and lungs, along with skin and eye evaluations

• Clinical trials: participation could be an option for advanced or refractory disease

• Support groups and psychological counseling: to assist with the emotional and social challenges associated with chronic illness