An 18-year-old man comes to the emergency department due to sudden-onset left-sided weakness. The patient has a seizure disorder but reports no seizures prior to current symptom onset. Neurological examination shows left-sided hemiparesis and hemianopia. On further questioning, the patient says that several of his family members also have a history of epilepsy and stroke, as shown in the pedigree diagram below (red arrow represents the patient). Which of the following is the most likely inheritance pattern of this patient's condition?

Question

An 18-year-old man comes to the emergency department due to sudden-onset left-sided weakness.  The patient has a seizure disorder but reports no seizures prior to current symptom onset.  Neurological examination shows left-sided hemiparesis and hemianopia.  On further questioning, the patient says that several of his family members also have a history of epilepsy and stroke, as shown in the pedigree diagram below (red arrow represents the patient).  Which of the following is the most likely inheritance pattern of this patient's condition?

Quizplus · Accepted Answer

Explanation: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), one of the most common mitochondrial myopathies, typically affects patients age <40 and presents with stroke-like episodes (eg, hemiparesis, vision abnormalities), seizures, muscle weakness, hearing loss, and lactic acidosis (due to mitochondrial dysfunction). Brain lesions, which are the result of defective mitochondrial energy production, are termed "stroke-like" as they do not correspond to vascular territories.Many mitochondrial myopathies are maternally inherited, with the condition being passed from the affected mother to male and female offspring (although heteroplasmy can result in variable clinical expression); however, male offspring do not further transmit the condition. This corresponds to the depicted pedigree: The grandmother of the patient had MELAS and transmitted it to all her children, but only her daughters (ie, the patient's aunt and mother) transmitted the disease to their offspring. heteroplasmy (Choice A) Autosomal dominant disorders affect 50% of all children born to an affected parent. The disease appears in consecutive generations, and father-to-son transmission is common. Although the depicted pedigree could occur with an autosomal dominant disorder, the clinical features consistent with MELAS and the fact that affected women passed the condition to all their offspring with no observable paternal transmission makes mitochondrial inheritance more likely. Autosomal dominant (Choice B) Autosomal recessive conditions affect about 25% of all children with 2 carrier parents. Offspring of a single affected parent are carriers for, but do not have, the disorder. As a result, the disease frequently skips generations. Autosomal recessive (Choice D) In X-linked dominant disorders, all female children of affected males have the condition, which is not consistent with this patient's pedigree findings for the second generation. X-linked dominant (Choice E) In X-linked recessive disorders, male offspring of a female carrier typically have a 50% chance of being affected, whereas female offspring typically have a 50% chance of being carriers. X-linked recessive Educational objective: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes is one of the most common mitochondrial myopathies and presents with stroke-like episodes, seizures, muscle weakness, hearing loss, and lactic acidosis. It is maternally inherited. As such, transmission occurs only through affected females and never through males.

An 18-Year-Old Man Comes to the Emergency Department Due to Sudden-Onset