Sign Up for a Free Account
  • Updated 08.22.2022
  • Released 04.07.1995
  • Expires For CME 08.22.2025

Pelizaeus-Merzbacher disease



Pelizaeus-Merzbacher disease is an X-linked recessive leukodystrophy caused by mutations of the proteolipid protein 1 (PLP1) gene. Pelizaeus-Merzbacher disease typically presents at a young age with congenital hypotonia, nystagmus, and ataxia. There are a few different forms of Pelizaeus-Merzbacher disease, depending on the type of mutation. They range on a clinical spectrum of disease from the severe connatal form to the uncomplicated spastic paraparesis syndrome. In this article, the authors describe the clinical features, pathophysiology, differential diagnosis, diagnostic workup, and current management of Pelizaeus-Merzbacher disease and its various forms.

Key points

• Pelizaeus-Merzbacher disease is caused by a variety of mutations in the PLP1 gene that lead to oligodendrocyte dysfunction and a reduction or absence of myelin in the central nervous system.

• The clinical presentation is on a spectrum, from the severe connatal form to an uncomplicated spastic paraparesis syndrome.

• Common clinical manifestations include nystagmus, hypotonia, ataxia, stridor, and, eventually, spastic paraplegia.

• As Pelizaeus-Merzbacher disease has X-linked inheritance, males are affected, and females are typically asymptomatic carriers.

• MRI shows diffuse and symmetric T2 hyperintensity of the white matter in the cerebrum and cerebellum, but diagnosis is confirmed with genetic testing for mutations in the PLP1 gene.

• Treatment is mostly symptomatic, but emerging gene therapies are being investigated.

Historical note and terminology

Pelizaeus-Merzbacher disease has historically been subdivided into clinical variants based on the age of onset and severity of clinical signs. "Classical" Pelizaeus-Merzbacher disease is the most common presentation and was first described by Friederich Pelizaeus, a physician (36). He discovered the disease when he came across a family with several males with nystagmus, spastic paraparesis, ataxia, and developmental delay. A few years later, Ludwig Merzbacher, a pathologist, proved the X-linked recessive inheritance pattern of Pelizaeus-Merzbacher disease (27). The "connatal" form of Pelizaeus-Merzbacher disease was described later and denotes clinically evident onset within the first few weeks of life and a more severe syndrome (41). Seitelberger described a “transitional” form of Pelizaeus-Merzbacher disease that was intermediate in clinical severity between connatal and classical disease (42). In 1964, Zeman and colleagues pointed out that Pelizaeus-Merzbacher disease is a dysmyelinating, rather than a demyelinating, entity and stressed the importance of clinical observation and the familial nature of the disorder rather than strict pathological criteria to define the condition (61). They also hypothesized that the defect in Pelizaeus-Merzbacher disease affected a myelin proteolipid. Saugier-Veber and colleagues discovered that some families with X-linked spastic paraparesis have PLP1 mutations (39). It must be noted that the phenotypes of Pelizaeus-Merzbacher disease and X-linked spastic paraparesis syndrome overlap.

This is an article preview.
Start a Free Account
to access the full version.

  • Nearly 3,000 illustrations, including video clips of neurologic disorders.

  • Every article is reviewed by our esteemed Editorial Board for accuracy and currency.

  • Full spectrum of neurology in 1,200 comprehensive articles.

  • Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660



ISSN: 2831-9125