Department of Pathology, University of Oklahoma Health Sciences Center

NeuroTest Question #74 Next question Previous question

Answer: Chromosome 9q34, 17p13.3, 16p13.3. Level of difficulty: 3 NeuroTest NeuroLearn NeuroHelp

Discussion: 

• Pathology of the case: The large cell (Þ) in the field is the key pathologic findings. This type of large, ballooned cells can be seen in several clinical setting. In the pediatric age group, the most probable situation is a cortical tuber obtained from patients with tuberous sclerosis. [Additional information on tuberous sclerosis]
• Tuberous sclerosis: tuberous sclerosis is a systemic disease with the brain as the most frequently affected organ. Clinically it is characterized by seizures, mental retardation and adenoma sebaceum. Pathologically, there is cortical tuber, subependymal nodules, and heterotopia in white matter of the brain. Subependymal giant cell astrocytoma (SEGA) is almost always associated with tuberous sclerosis.
• Skin lesions in tuberous sclerosis: Although skin lesion is not mentioned in the question, they are the most common findings outside the central nervous system. The classic skin lesion is adenoma sebacum (facial angiofibroma) which usually appears in between 2 and 5 years of age. Other skin lesions including hypomelanotic macule (occurs in 90% of patients, sometimes discovered at birth), peri- or subuncal fibroma, shagreen patches (fibrous hamartomas of dorsal surfaces, rarely seen before puberty), poliosis and leukotrichia.

• Genetics of tuberous sclerosis: Autosomal dominant with very high penetrance. Occurrence of affected siblings with apparently unaffected parents is extremely rare. TSC1 gene on chromosome 9q34 (gene product is hamartin) and TSC2 gene (gene product is tuberin) on chromosome 16p13.3 are involved. Sporadic cases were first thought of resulted from mutation but CT scans of asymptomatic family members revealed a significant numbers with abnormalities.

Comment: KarMing-Fung@ouhsc.edu