A 28-year-old man is evaluated for abnormal movements of the hands and face. The patient reports that he started experiencing involuntary grimacing a year ago, which has gradually worsened. He is taking a selective serotonin reuptake inhibitor for major depression but has not taken any antipsychotic medications. His 52-year-old father was diagnosed with an inherited movement disorder 2 months ago. Physical examination shows normal strength and normal deep tendon reflexes. No sensory deficits are noted. Which of the following best explains the difference in disease presentation between this patient and his father?

Question

A 28-year-old man is evaluated for abnormal movements of the hands and face.  The patient reports that he started experiencing involuntary grimacing a year ago, which has gradually worsened.  He is taking a selective serotonin reuptake inhibitor for major depression but has not taken any antipsychotic medications.  His 52-year-old father was diagnosed with an inherited movement disorder 2 months ago.  Physical examination shows normal strength and normal deep tendon reflexes.  No sensory deficits are noted.  Which of the following best explains the difference in disease presentation between this patient and his father?

Quizplus · Accepted Answer

11ec160b_376b_422c_9249_99338c03fcab_MD0001_00 This patient presenting with involuntary movements, depression, and a family history of a movement disorder likely has Huntington disease (HD), which typically manifests with the triad of movement disorder (chorea), behavioral abnormalities (aggressiveness, apathy, or depression), and dementia. HD is caused by an expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats. Most patients develop symptoms in their 40s or 50s, but an earlier age of onset and more severe symptoms are associated with a larger number of trinucleotide repeats. During spermatogenesis, CAG repeats in the abnormal HTT gene (chromosome 4p) can rapidly increase (much more than during oogenesis). Therefore, patients who receive an abnormal gene from their fathers tend to develop the disease earlier in life. The tendency for clinical symptoms to worsen and/or occur earlier in subsequent generations is called anticipation. Anticipation is common in disorders associated with trinucleotide repeats, as in Fragile X syndrome, myotonic dystrophy, and Friedreich ataxia. (Choice B) Genomic imprinting is a selective inactivation of the genes of either maternal or paternal origin. It results in Prader-Willi and Angelman syndromes, which involve deletions of the same region on chromosome (15q) but have very different clinical manifestations due to the differential expression of parental genes. When the chromosome with the deleted region comes from the father, the lack of expression of maternally imprinted genes results in Prader-Willi syndrome. Likewise, deletions affecting the maternal chromosome result in Angelman syndrome due to absent expression of paternally imprinted genes. (Choice C) HD is transmitted in an autosomal dominant pattern with complete penetrance, which means that a child who inherits the abnormal gene will inevitably develop Huntington disease. (Choice D) Microdeletion is the loss of genetic material too small to be visible via light microscopy. For example, microdeletion of 22q11 is responsible for DiGeorge syndrome. (Choice E) The presence of 2 populations of cells with different genotypes in one patient resulting in the mixed expression of disease is called mosaicism. Examples of mosaicism include milder forms of Turner (genotype 46XX/45X0), Klinefelter (46XY/47XXY), and Down syndromes. (Choice F) Sometimes, one gene mutation leads to multiple, seemingly unrelated phenotypic abnormalities, a genetic phenomenon termed pleiotropy. Educational objective: An increased number of trinucleotide repeats on the HTT gene is associated with Huntington disease. The larger the number of repeats, the earlier the onset of the disease. Trinucleotide expansion occurs more frequently during paternal transmission, causing a genetic phenomenon called anticipation. __________ References: Genetics and neuropathology of Huntington's disease. (http://www.ncbi.nlm.nih.gov/pubmed/21907094)

A 28-Year-Old Man Is Evaluated for Abnormal Movements of the Hands