A 42-year-old man develops progressive choreiform movements, personality change, and cognitive decline. His father had similar symptoms beginning at age 45. Genetic testing reveals a trinucleotide repeat expansion. The affected gene is located on the short arm of chromosome 4 and encodes a protein with a polyglutamine tract. The pathological hallmark is selective atrophy of which structure?

• A Caudate nucleus and putamen (striatum) ✓
• B Substantia nigra pars compacta
• C Globus pallidus
• D Subthalamic nucleus

Explanation

This is Huntington disease, an autosomal dominant disorder caused by CAG trinucleotide repeat expansion in the huntingtin (HTT) gene on chromosome 4p. The pathological hallmark is selective atrophy of the caudate nucleus and putamen (striatum), with medium spiny GABAergic neurons being most vulnerable. Substantia nigra atrophy is seen in Parkinson disease. Subthalamic nucleus lesion causes hemiballismus, not atrophy.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.