Question

A 21-year-old man comes to the physician complaining of recent onset of vision loss. Neuroimaging studies reveal several small infarcts in the occipital lobes bilaterally. Skeletal muscle biopsy reveals ragged appearing muscle fibers. The patient's 56-year-old mother has chronic intermittent muscle weakness and an elevated serum lactate level. The patient's family history is also significant for a maternal uncle who developed hemiplegia at the age of 35. Assuming each of these family members has the same condition, the variability in their clinical findings is best explained by:

A. Variable penetrance
B. Mosaicism
C. Uniparental disomy
D. Anticipation
E. Heteroplasmy

Answer 1

The clinical variability among the family members described is best explained by heteroplasmy, the presence of a mixture of more than one type of mitochondrial DNA within a cell, which can cause variable expression of mitochondrial disorders.

Step-by-step explanation:

The variability in clinical findings for the patient, his mother, and maternal uncle with the same condition is best explained by heteroplasmy. Heteroplasmy refers to the presence of a mixture of more than one type of mitochondrial DNA within a cell or individual. It can lead to variability in mitochondrial diseases because the distribution of mitochondrial DNA mutations can vary in different tissues and between family members.

The combination of neuroimaging findings showing infarcts in the occipital lobes, a skeletal muscle biopsy revealing ragged appearing muscle fibers, chronic intermittent muscle weakness, elevated serum lactate level, and hemiplegia in various family members points toward a mitochondrial disorder with heteroplasmic inheritance.

Heteroplasmy can lead to differing levels of mitochondrial dysfunction in different tissues, which explains why symptoms can vary widely even among individuals within the same family.