In the context of Charcot-Marie-Tooth disease, which region is most commonly affected initially?

In Charcot-Marie-Tooth disease (CMT), the lower leg muscles are most commonly affected initially due to the nature of the disease, which primarily targets peripheral nerves. CMT is a hereditary neuropathy that leads to the degeneration of the peripheral nerves, primarily affecting the motor and sensory nerves.

The initial symptoms often manifest in the muscles below the knee, leading to weakness and atrophy in the lower extremities. This can result in challenges such as foot drop, which is characterized by difficulty in lifting the front of the foot during walking. The lower leg muscles, particularly the anterior tibialis and peroneal muscles, experience the effects of nerve damage, and patients may exhibit high-steppage gait and other manifestations of lower extremity weakness.

In contrast, the upper arm muscles, hand and forearm, as well as abdominal muscles can also be involved as the disease progresses but are not typically the first regions affected. This progressive nature of CMT highlights the underlying genetic and neuropathological factors that preferentially impact the lower extremities at the onset of the disease.