Question

A 32-year-old man presents to the primary care clinic to establish care. He reports worsening stiffness in his hands over the past three years, noting particular difficulty releasing his grip after turning a doorknob or shaking hands. He also complains of excessive daytime sleepiness and recent-onset blurry vision. Physical examination reveals frontal baldness, bilateral ptosis, and wasting of the temporalis muscles. Slit-lamp examination confirms bilateral posterior subcapsular cataracts. An electrocardiogram demonstrates a first-degree atrioventricular block. Family history is significant for a mother who developed mild distal muscle weakness in her late 50s. Furthermore, the patient's sister recently gave birth to a male infant who has severe generalized hypotonia and requires mechanical ventilation. Which of the following genetic principles best explains the generational differences in disease severity and age of onset observed in this family?