Pelizaeus-Merzbacher disease (PMD) is a rare X-linked leukodystrophy, which means that the mutated gene is on the X chromosome, one of the two sex chromosomes.

Males carry only one copy of the X chromosome, while females carry two copies. Therefore, this disease affects only males, while females are "carriers” and do not show any symptoms of PMD. However, female carriers are at higher risk for developing dementia and stiffness in the lower extremities later in life. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. The affected gene is called PLP1, which provides instructions for producing a protein referred to as proteolipid protein. This protein is an important part of the myelin sheath, and changes in this protein will result in a lack of myelin insulation of axons, the brain’s nerve cables.


The classic form of PMD presents with abnormal eye movements, with onset during the first months of life. Patients show delays in motor skills, develop muscle stiffness and unsteadiness, and deteriorate cognitively before age 2. Involvement of the optic nerve and the vocal cords are common.

The connatal form of PMD presents with abnormal eye movements at birth, severe impairment of vocal cords, and very early onset contractures of joints. Seizures are very common.

Patients with a PLP1 gene mutation may also present later in life with predominant muscle stiffness in lower extremities, a condition called spastic paraplegia type 2 (SPG2). These patients do not show impairment in cognitive function.


Very recently, a phase I exploratory clinical trial of neural stem cell transplantation performed in four boys with PMD showed some mild, but measurable, gains in motor function. A larger clinical trial is needed to determine whether this strategy is beneficial for patients with PMD.

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