A 26-year-old woman is being evaluated for a possible inherited disorder. She has a 6-year history of generalized tonic-clonic seizures, and a year ago, she had partial loss of vision due to an occipital infarction. Her mother has chronic intermittent muscle weakness and lactic acidosis, and her maternal uncle has hemiplegia. Skeletal muscle biopsy of the patient shows ragged-appearing muscle fibers. After further evaluation, all the affected family members are found to suffer from the same inherited disease. Pedigree analysis is shown in the image below. Which of the following is the most likely explanation for the variability of clinical manifestations in the affected family members?

Question

A 26-year-old woman is being evaluated for a possible inherited disorder.  She has a 6-year history of generalized tonic-clonic seizures, and a year ago, she had partial loss of vision due to an occipital infarction.  Her mother has chronic intermittent muscle weakness and lactic acidosis, and her maternal uncle has hemiplegia.  Skeletal muscle biopsy of the patient shows ragged-appearing muscle fibers.  After further evaluation, all the affected family members are found to suffer from the same inherited disease.  Pedigree analysis is shown in the image below.  Which of the following is the most likely explanation for the variability of clinical manifestations in the affected family members?

Quizplus · Accepted Answer

Eductional Objective: The presence of lactic acidosis and ragged skeletal muscle fibers histologically suggests a mitochondrial myopathy.  Variable clinical expressions in affected family members can occur due to heteroplasmy, which is the coexistence of distinct versions of mitochondrial genomes in an individual cell.

A 26-Year-Old Woman Is Being Evaluated for a Possible Inherited