Pelizaeus-Merzbacher disease (PMD) is an X-linked leukodystrophy which is characterized by an arrest in myelin development. 

Clinical presentation

Male patients who may present with 

• pendular eye movements (nystagmus)

• hypotonia

• pyramidal disease

• ataxia

Pathology

Genetics

Pelizaeus-Merzbacher disease is the result of abnormalities of the proteolipidprotein (PLP1) gene locus at Xq22. This can be either a mutation, deletion or duplication (most common) ⁴.

Subtypes

Traditionally Pelizaeus-Merzbacher disease has divided into two subtypes:

• classic 

• connatal: more rare and severe ⁵

Radiographic features

CT

CT features, as is the case with many leukodystrophies, are non-specific and may show hypoattenuating white matter with progressive white matter atrophy.

MRI

Features include:

• T1: lack of myelination, often seen as low T1 signal regions typically involving internal capsule, proximal corona radiata and the optic radiation

• T2: near complete absence of expected low signal in the supratentorial region

  • abnormal signal can either be diffuse or patchy

  • if there is patchy involvement, a characteristic tigroid appearance may be seen ⁵

  • may also show cortical sulcal prominence due to atrophy ⁴

  • white matter volume may be decreased ⁴

  • may also involve cerebellum and brainstem ⁴

• MR spectroscopy

  • affected areas often show a reduction in the NAA peak ⁴

  • decreased choline (due to hypomyelination) ⁴

History and etymology 

Named after Friedrich Christoph Pelizaeus (1851-1942), a German neurologist, and Ludwig Merzbacher (1875-1942), an Italian neuropathologist and psychiatrist. 

Differential diagnosis

Although numerous other leukodystrophies are in the general differentials, specific entities to be considered include: 

• Pelizaeus-Merzbacher-like disease (mutations of GJA12 at 1q41-q42 or MCT8 at Xq13.2)

• 18q- deletion (18q22.3 q23)

• Salla disease (SLC17A5 gene at 6q14-q15).