At the clinic, 32 year old mary comes with her 6 year old son thomas, after noticing he’s often clumsy, weak, and has trouble climbing the stairs of their house. Mary is worried because she had a brother who presented the same symptoms as a child, and developed progressive weakness, until he passed away at 23 years old due to respiratory problems. Upon physical examination, the physician notices that thomas has scoliosis and thick calves. Later that day, 29 year old sarah comes to the clinic with her 10 year old son mike because of progressive muscle weakness and fatigue, as well as vomiting and loss of appetite. In addition, she mentions that he has experienced seizures.
Based on the clinical findings, the physician concludes that both children have some form of inherited muscular disorder, and orders genetic testing to confirm the diagnosis. Now, let’s go over the two main groups: muscular dystrophies and mitochondrial myopathies.
Muscular dystrophies are a group of genetic disorders characterized by muscle degeneration and weakness. Within that group, dystrophinopathies are the most common, and this includes duchenne muscular dystrophy, or dmd for short, and becker muscular dystrophy, or bmd.
Both duchenne and becker result from mutations in the dystrophin gene, which is found on the x chromosome. For your exams, remember that these are x-linked recessive disorders, which means that all carrier males develop the disease, because they only have one x chromosome and thus one dystrophin gene available. On the other hand, females have two x chromosomes, so even if they have a defective dystrophin gene on one x chromosome, they still have another functional one. However, only one x chromosome gets expressed and the other is inactivated through a process called x-inactivation or lyonization. This inactivation is random which means that every cell could have a chance of having the mutated x chromosome be the active copy. If this is the case for more than half of the muscle cells, they will be a manifesting carrier who will develop symptoms. People with more cells with the active mutated x chromosome will have more severe symptoms and quicker disease progression. If less than half of their cells have the active mutated x chromosome, they’ll be an asymptomatic carrier and won’t develop symptoms.