A 3-year-old boy is being evaluated for recurrent generalized seizures and developmental delay. Physical examination is notable for scattered hypopigmented skin patches. MRI of the head reveals multiple masses, most of which line the ependymal surfaces of the lateral ventricles, and some are calcified, as shown in the below image. Which of the following is the most likely underlying cause of this patient's brain lesions?

Question

A 3-year-old boy is being evaluated for recurrent generalized seizures and developmental delay.  Physical examination is notable for scattered hypopigmented skin patches.  MRI of the head reveals multiple masses, most of which line the ependymal surfaces of the lateral ventricles, and some are calcified, as shown in the below image.  Which of the following is the most likely underlying cause of this patient's brain lesions?

Quizplus · Accepted Answer

11ec160b_39a7_4f43_9249_bbe7e06bb29a_MD0001_00 This patient's findings are consistent with tuberous sclerosis complex (TSC), an autosomal dominant disorder caused by mutations in the genes coding for the tumor suppressor proteins hamartin and tuberin (ie, TSC1 and TSC2). Unrestricted cellular proliferation results in the formation of hamartomas, or benign overgrowths of disorganized tissue. They develop primarily in the skin and CNS but may involve the heart, kidneys, eyes, and gastrointestinal tract. Seizures and developmental delay are often the first presenting signs of TSC. Most patients have characteristic cortical glioneuronal hamartomas (tubers) in the cerebral cortex and subependymal nodules lining the lateral ventricles, as seen on this patient's MRI. These brain hamartomas are composed of atypical glial and neuronal elements and often calcify. The first dermatologic manifestation of TSC is usually ash-leaf spots (ie, hypopigmented macules). Other classic cutaneous findings usually develop later and can include facial angiofibromas (ie, adenoma sebaceum), periungual fibromas, and hamartomatous plaques of connective tissue (ie, shagreen patches). (Choice B) Lysosomal metabolite accumulation occurs with lysosomal storage diseases (eg, Tay-Sachs, Niemann-Pick), which can cause seizures and neurologic decline. However, symmetric areas of demyelination would be expected on MRI rather than the discrete calcifications seen in this case. (Choices C, D, and E) Seizures can be the presenting sign of malignant lymphoid proliferation (ie, CNS lymphoma) or CNS infection (eg, Mycobacterium tuberculosis, tapeworm Taenia solium). However, characteristic MRI findings include ring-enhancing lesions, not subependymal nodules. Moreover, hypopigmented macules are not associated with these conditions. Educational objective: Tuberous sclerosis complex is an autosomal dominant disorder characterized by benign hamartomas of the brain (ie, cortical glioneuronal hamartomas and subependymal nodules) and skin. Seizures and ash-leaf spots are common presenting signs.

A 3-Year-Old Boy Is Being Evaluated for Recurrent Generalized Seizures