A 23-year-old man is being evaluated for myoclonic epilepsy of recent onset. The episodes are short-lived and triggered by startle. Physical examination reveals proximal muscle weakness. Gomori trichrome stain of a muscle biopsy specimen shows muscle fibers with a blotchy red appearance. No family history is available because the patient is adopted. What is the probability that this patient's one offspring will inherit the disease?
Blotchy red muscle fibers on Gomori trichrome stain are characteristic of the mitochondrial myopathies. In these conditions, abnormal mitochondria accumulate under the sarcolemma of muscle fibers. The fibers have an irregular shape and size on cross section. For this reason, the mitochondrial myopathies are also known as the "red ragged fiber" diseases. Electron microscopy of the affected muscle reveals an increased number of enlarged, abnormally shaped mitochondria.
The most important mitochondrial myopathies are myoclonic epilepsy with ragged red fibers (MERRF, described in this vignette), Leber optic neuropathy (blindness), and mitochondrial encephalopathy with stroke-like episodes and lactic acidosis (MELAS). Each of these diseases is the result of a mitochondrial gene mutation.
The mitochondrial diseases are caused by mutations, deletions or duplications of mtDNA. Because sperm mitochondria do not pass into the ovum during fertilization, only maternal mitochondria are transmitted to the fetus. Mitochondrial diseases, therefore, have maternal inheritance. For this reason the male patient described in this vignette will not transmit the disease to his progeny.
(Choice B) No pure single-gene inherited disease shows 75% transmission. There may be 75% transmission for a disease with variable penetrance.
Individuals affected by a disease with autosomal dominant inheritance receive one copy of the abnormal gene from one parent. The chance that an affected person will transmit the disease to his/her child is 50% (Choice C) if the parent is heterozygous for the given disease. If the parent is homozygous, there is a 100% chance (Choice A) of transmission.
(Choice D) Autosomal recessive diseases occur when the individual inherits two copies of the mutated gene (one from each parent). If both parents are carriers, there is a 25% chance that the child will be affected.
Educational Objective:
"Red ragged" muscle fibers are seen in mitochondrial diseases. Muscle fibers have this appearance because abnormal mitochondria accumulate under the sarcolemma. Mitochondrial diseases show maternal inheritance.