tuberculosis brain scan

Primary steps for primary care: Tuberous sclerosis complex (TSC)

TSC is an autosomal dominant neurocutaneous disorder affecting one in every 6,000-10,000 people. TSC manifests with multi-organ involvement including the skin, central nervous system, heart, lungs, eyes and kidneys. The most common identified cause is a variant in the tumor suppressor genes TSC1 or TSC2, on chromosomes 9p34 and 16p13, respectively. Abnormalities of these genes result in abnormal proteins, hamartin and tuberin, causing a permanent activation of the mTOR pathway which results in the formation of hamartomas in multiple organs. TSC may often come to the attention of primary care providers through recognition of typical skin findings or new onset of seizures.

What are the clinical manifestations of TSC?

Cutaneous manifestations

  •  Ash-leaf spots: Hypopigmented leaf-shaped macules, present at birth. When clinically suspected, a careful Wood’s lamp skin examination may be needed.
  • Facial angiofibromas: Appear within the first decade of life, papules that affect mainly the malar region, nose, forehead and chin.
  • Ungual fibromas.
  • Connective tissue nevi: Shagreen patches, located mainly in the lumbosacral region.
  • Gingival fibromas and enamel pits.

Renal manifestations

  • Renal angiomyolipomas: Extremely common, progressively enlarge in adolescence and early adulthood.
  • Renal cysts.

Pulmonary manifestations

  • Lymphangioleiomyomatosis: May affect pulmonary function and primarily seen in adult females.

Cardiac manifestations

  • Rhabdomyoma: Typically manifest in the fetus and newborn, commonly asymptomatic, and often begin to involute within the first year of life.

Neurological manifestations

  • Epilepsy: Present in 70-90% and may present at any age. Typically, seizures are difficult to treat. Careful attention is needed to monitor for infantile spasms, as 10-25% of people with infantile spasms have TSC and this could be the first presentation of TSC. Urgent evaluation and treatment is needed if infantile spasms occur.
  • Intellectual deficiency, autism spectrum disorder, mood disorders: Children may present with failure to meet developmental milestones.
  • Neuroimaging findings (Figure 1): Cortical dysplasias, cortical and subcortical tubers, subependymal nodules, subependymal giant cell astrocytoma.

Ophthalmologic abnormalities

  • Retinal hamartoma: Present in 30-50%.

How is TSC diagnosed?

TSC can be diagnosed clinically when a combination of major and minor features are present (Table 1). Genetic testing can also be used to support or confirm the diagnosis in the right clinical settings.

Table 1

Major criteriaMinor criteria
Hypomelanotic macules (> 3, > 5mm in diameter)“Confetti” skin lesions
Angiofibromas (> 3)Dental enamel pits (> 3)
Ungual fibromas (> 2)Intraoral fibroma (> 2)
Shagreen patchRetinal achromic patch
Multiple retinal hamartomas (> 2)Multiple renal cysts
Cortical dysplasiaNonrenal hamartomas
Subependymal nodules 
Subependymal giant cell astrocytoma 
Cardiac rhabdomyoma 
Lymphangioleiomyomatosis 
Angiomyolipomas (> 2) 
Adapted from Northrup and Krueger

Definitive diagnosis: Presence of 2 major criteria or 1 major and 2 minor criteria.

Probable diagnosis: Presence of 1 major criterion or 2 or more minor criteria.

What is the initial evaluation and subsequent care for TSC?

The management of TSC typically requires a multidisciplinary approach depending on the manifestations of the disease. Care can be coordinated through a TSC clinic, such as the Genetic Epilepsy Clinic at Cook Children’s[SPM1] . Often the treatment team will include members from Genetics, Neurology, Ophthalmology, Pulmonology, Nephrology and Odontology. Routine monitoring for manifestations of TSC are included in the evaluation guidelines below (Table 2). If a primary care provider suspects TSC, initial workup should include MRI of brain and kidneys, along with cardiac echo.

Table 2

Organ systemRecommendations
BrainBrain MRI every 1-3 years, until age 25, electroencephalogram (EEG) as needed, TSC associated neuropsychiatric disorder (TAND) screen annually
HeartEchocardiogram every 1-3 years, until involution of rhabdomyoma, electrocardiogram (EKG) every 3-5 years
KidneysAnnual blood pressure measurement, annual glomerular filtration rate, abdominal MRI every 1-3 years
LungsPulmonary function tests annually, high-resolution chest computed tomography (CT) scan every 5-10 years
Skin, eyesAnnual clinical examination
TeethBi-annual clinical examination
GeneticsThree-generation family history, consider genetic testing, genetic counseling
Adapted from Carapetian Randle

To refer a patient to the Tuberous Sclerosis/Genetic Epilepsy Clinic at Cook Children’s, call 682-885-2500.

Figure 1:


Contributing staff

Rolla Shbarou, M.D.
Neurology, Cook Children’s

Meet Dr. Shbarou

Related programs

Genetic epilepsy, tuberous sclerosis


Cook Children’s Neurosciences team

Great outcomes begin with great input. Having a medical system where every department, doctor, and care team member works together means that your child can have quick access to testing, diagnosis and treatment, and that means better outcomes now and in the future.

Contact the Jane and John Justin Neuroscience Center at Cook Children’s with your questions at 682-885-2500.

References

1.  Northrup and Krueger; International Tuberous Sclerosis Complex Consensus Group. Tuberous Sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatric Neurol. 2013;49(4):243-254.

2.  Portocarrero, Larissa Karine Leite et al. Tuberous Sclerosis Complex: review based on new diagnostic criteria. An Bras Dermatol. 2018;93(3):323-31.

3. Carapetian Randle, Stephanie. Tuberous Sclerosis Complex: A review. Pediatr Ann. 2017;46(4):e166-e171.

You Might Also Like