What other abnormal findings are likely to be discovered in a 5-month-old boy with abnormal movements, global developmental delay, and dermatologic findings consistent with Tuberous Sclerosis Complex (TSC)?

Hamartomas in Brain, Heart, and Kidneys

This 5-month-old boy with tuberous sclerosis complex (TSC) will most likely have hamartomas discovered in the brain, heart, and kidneys upon further evaluation.

Clinical Presentation Confirms TSC Diagnosis

The clinical picture is diagnostic for TSC based on multiple major and minor criteria 1:

• Infantile spasms (brief stiffening of arms and legs) are the characteristic seizure type in TSC infants 1
• Hypopigmented macules (ash-leaf spots) visible under Wood's lamp are a major diagnostic criterion 1
• Ungual fibromas at the nail cuticles are pathognomonic skin findings 1
• Shagreen patch (the irregular non-erythematous plaque on the back) is another major criterion 1
• Global developmental delay reflects underlying cortical tubers and neurological involvement 1

Expected Hamartomatous Lesions in TSC

Brain Hamartomas

Cortical tubers, subependymal nodules, and potential subependymal giant cell astrocytomas (SEGAs) will be present in the brain 2. These brain lesions are characterized by:

• Cortical/subcortical tubers with disorganized cortical lamination and dysplastic neuronal elements 3
• Subependymal nodules consisting of large abnormal glial cells 3
• SEGAs that can develop from subependymal nodules over time 2

All patients with suspected TSC should undergo noncontrast brain MRI at diagnosis to assess for these lesions 2. The brain lesions directly cause the seizures and developmental delays seen in this patient 1.

Cardiac Hamartomas

Cardiac rhabdomyomas are highly likely in this infant 2. Key features include:

• Two-thirds of newborns with TSC have one or more cardiac rhabdomyomas 1
• These are largest during the neonatal period and typically regress with time 1
• Echocardiogram should be performed at diagnosis, especially in children <3 years old 2
• If positive and the patient is asymptomatic, follow-up echocardiograms every 1-3 years until regression 2

Renal Hamartomas

Angiomyolipomas (AMLs) and/or renal cysts will likely be discovered 2. Important considerations:

• 70-80% of TSC patients develop angiomyolipomas, though median age of detection is 8-13 years 1
• Approximately 50% develop cystic kidney disease, with median detection age of 3 years 1
• Both can develop in the first months of life, justifying early screening 2, 1
• Baseline renal MRI should be performed at diagnosis, ideally concurrent with brain MRI 2
• Follow-up with abdominal ultrasound every 1-3 years until age 12, then transition to MRI 2

Why Other Options Are Incorrect

Bilateral Vestibular Schwannomas

These are pathognomonic for neurofibromatosis type 2 (NF2), not TSC 1. NF2 presents with different cutaneous findings (café-au-lait macules, not hypopigmented macules) and lacks the cardiac and renal hamartomas characteristic of TSC.

Cerebellar Hemangioblastoma

This is associated with von Hippel-Lindau (VHL) syndrome, not TSC 1. VHL patients develop retinal and CNS hemangioblastomas, renal cell carcinomas, and pheochromocytomas, but not the cortical tubers or cardiac rhabdomyomas seen in TSC.

Facial Port-Wine Stain (V1/V2 Distribution)

This finding is characteristic of Sturge-Weber syndrome, not TSC 2. Sturge-Weber involves leptomeningeal angiomatosis and glaucoma, but lacks the systemic hamartomas of TSC.

Optic Glioma

While retinal astrocytomas occur in 30-50% of TSC patients 2, optic gliomas are more characteristic of neurofibromatosis type 1 (NF1) 1. TSC patients require annual dilated fundoscopic examination to detect retinal hamartomas 2.

Critical Management Pitfalls

• Normal kidney imaging in infancy does not exclude future development of renal lesions—all TSC patients require lifelong kidney surveillance 2, 1
• Cardiac rhabdomyomas can cause neonatal heart failure if large or multiple, requiring urgent echocardiography 2
• Brain MRI surveillance every 1-3 years until age 25 is essential to monitor for SEGA development, which can cause obstructive hydrocephalus 2
• Refer to a TSC specialty center for coordinated multidisciplinary management 2