A 37 year old man is referred to a psychiatrist because of erratic behavior. The man had been adopted in infancy, so his family history is not known. Over the next year, he develops uncontrollable erratic movements, such that attempts to pick up a cup or use a pencil produce sudden uncontrolled lurches. When he tries to walk, he staggers, thrusts, and abruptly changes direction. Eventually, with disease progression, he develops increasing rigidity and is unable to move, and finally dies ten years after the onset of symptoms. Which of the following changes would most likely be seen on examination of his brain at autopsy?
A. Depigmentation of the substantia nigra and locus ceruleus
B. Diffuse cortical atrophy with relative sparing of primary motor and sensory areas
C. Selective frontal and temporal lobe atrophy
D. Striking degeneration of the caudate nucleus
E. Widespread neuronal loss and gliosis in subcortical sites
The correct answer is D. The disease is autosomal dominant Huntington’s chorea. The question stem describes a typical clinical progression (the family history is usually strikingly positive). Pathological findings include severe atrophy of the caudate nucleus (with loss of medium-sized spiny neurons), less severe involvement of the putamen and cerebral cortex, and dilation of the lateral ventricles apparent on CT and MRI studies. The disorder is known to be caused by expansion of a CAG trinucleotide repeat in a gene on the short arm of chromosome 4 coding for a protein called huntingtin. There is no effective therapy.
The wife of a 49 year old male patient brings him to the emergency room and says that his memory has progressively gotten worse over the last several years. She also says his personality has been changing. The physician notes abnormal writhing movements of the man’s limbs and hyperreactive reflexes. MRI reveals a loss of volume in the neostriatum and cortex. This disease
is inherited via an
A. autosomal dominant trait
B. autosomal recessive trait
C. x-linked dominant trait
D. x-linked recessive trait
The correct answer is A. This patient has Huntington’s disease, which has autosomal dominant inheritance. It is characterized by severe degeneration of the caudate nucleus along with degenerative changes in the putamen and cortex. In addition to chorea, these patients frequently suffer from athetoid (writhing) movements, progressive dementia, and behavioral disorders.