Dermatology MCQ - Genetic Disorders - Tuberous Sclerosis

A 6-month-old infant presents with a new-onset seizure characterized by infantile spasms. On physical examination, you note three hypomelanotic macules on the trunk that are leaf-shaped ("ash-leaf spots"). A Wood's lamp examination enhances their visibility. What is the most likely diagnosis and the most critical initial diagnostic test to evaluate for a life-threatening complication?

A. Neurofibromatosis type 1; MRI brain to evaluate for optic pathway glioma.
B. Tuberous Sclerosis Complex; echocardiogram to evaluate for cardiac rhabdomyomas.
C. Incontinentia Pigmenti; skin biopsy to confirm the inflammatory vesicular stage.
D. Hypomelanosis of Ito; EEG to characterize seizure type.
E. Sturge-Weber syndrome; MRI brain with contrast to look for leptomeningeal angioma.

Correct Answer: B. Tuberous Sclerosis Complex; echocardiogram to evaluate for cardiac rhabdomyomas.

Answer and Explanation

The correct answer is B. This question describes the classic early presentation of Tuberous Sclerosis Complex (TSC). The key clues are the infantile spasms (a common and often initial neurological manifestation) and the presence of multiple hypomelanotic macules (ash-leaf spots), which are often the first cutaneous sign and are best seen with a Wood's lamp. While brain imaging is crucial, in a newly diagnosed infant, the most critical initial test is an echocardiogram. This is to evaluate for cardiac rhabdomyomas, which are benign tumors present in up to 80% of infants with TSC. Although often asymptomatic, they can cause arrhythmias, outflow obstruction, or heart failure, and their presence can be a major diagnostic clue.

Why the Other Options are Incorrect:

• A. Neurofibromatosis type 1: NF1 causes café-au-lait macules (hyperpigmented), not hypopigmented macules. Seizures can occur but are not typically infantile spasms as a presenting sign.

• C. Incontinentia Pigmenti: This X-linked disorder presents in female infants with a vesicular/blistering stage followed by verrucous and then hyperpigmented stages, not stable hypopigmented macules.

• D. Hypomelanosis of Ito: This is a diagnosis of exclusion characterized by linear or whorled hypopigmentation along Blaschko's lines, often associated with neurological and skeletal issues. However, the classic triad of infantile spasms + hypomelanotic macules + cardiac tumors is pathognomonic for TSC.

• E. Sturge-Weber syndrome: This presents with a port-wine stain (capillary malformation), not hypopigmented macules, and seizures are typically focal, not infantile spasms.

Additional High-Yield Information for Exams:

• Diagnostic Criteria: Requires 2 major features or 1 major + 2 minor features.

  • Major Features: Hypomelanotic macules (≥3, >5mm), facial angiofibromas or forehead plaque, shagreen patch (connective tissue nevus), ungual fibromas, retinal hamartomas, cortical tubers, subependymal nodules (SEN), subependymal giant cell astrocytoma (SEGA), cardiac rhabdomyoma, lymphangioleiomyomatosis (LAM), renal angiomyolipomas.

  • Minor Features: "Confetti" skin lesions, dental enamel pits, intraoral fibromas, etc.

• Genetics: Autosomal dominant, but ~2/3 are de novo. Caused by mutations in TSC1 (hamartin) or TSC2 (tuberin) genes, which are tumor suppressors in the mTOR pathway.

• Clinical Features:

  • Neurologic: Infantile spasms, other seizure types, intellectual disability, autism spectrum disorder, SEGAs (can cause obstructive hydrocephalus).

  • Cutaneous: Ash-leaf spots (present at birth), facial angiofibromas (appear in childhood), shagreen patch, periungual fibromas.

  • Renal: Angiomyolipomas (common, can bleed) and renal cysts.

  • Cardiac: Rhabdomyomas (often regress spontaneously).

  • Pulmonary: LAM (almost exclusively in women, causes cystic lung disease).

• Differential Diagnosis: The combination of seizures and hypopigmented macules is highly specific for TSC. Other causes of infantile spasms (metabolic, structural) lack the skin findings.

• Associated Conditions & Prognosis:

  • Prognosis: Variable. Seizure control and prevention of SEGA/LAM/renal complications are major determinants of morbidity. Lifespan can be normal with good management.

• Management & Rationale:

  • Rationale: Lifelong, multidisciplinary surveillance to detect and treat complications early.

  • First-line/Obligatory Baseline & Surveillance:

    1. Cardiac: Echocardiogram at diagnosis in infants/children.

    2. Neurologic: MRI brain at diagnosis and every 1-3 years in children to monitor for SEGA. EEG if seizures are suspected.

    3. Renal: Renal ultrasound every 1-3 years to monitor angiomyolipomas.

    4. Dermatologic: Annual skin exam.

  • Targeted Therapy: mTOR inhibitors (e.g., everolimus, sirolimus) are revolutionary. They are approved for: SEGA (shrinks tumors), renal angiomyolipoma, and LAM. They can also reduce seizure frequency.

  • Specific Treatments: Vigabatrin for infantile spasms, epilepsy surgery for refractory seizures, embolization/nephron-sparing surgery for large angiomyolipomas.