Pelizeaus-Merzbacher Disease

Clinical Characteristics
Ocular Features: 

Nystagmus is the major ocular feature in this disease and may appear as early as the first weeks of life in severe cases.  However, more mildly affected individuals may never have nystagmus and, further, it can disappear later.  The ocular movements are usually pendular but may have horizontal and rotatory components as well.  The presence of nystagmus is diagnostically important as it is an uncommon finding in other leukodystrophies.

Systemic Features: 

The classic disease is infantile in onset with hypotonia, titubation, weakness, stridor, respiratory problems, and even seizures often noted in the first weeks of life.   Ataxia, spasticity and cognitive delay are soon apparent.  Infants affected early and severely may never achieve normal motor or mental milestones whereas those less severely affected may at some point ambulate and acquire some language skills.  However, acquired skills may be lost by adolescence.  Survival to the sixth decade of life is common but those with the most severe form of disease may not live beyond the second decade. 

This is an X-linked recessive disorder in which only males have the complete syndrome.  However, multiple carrier females have been studied and many have subtle evidence of disease mainly in gait and motor control.


Pelizeaus-Merzbacher disease is the result of mutations in an X-linked gene PLP1 (Xq22).  It is inherited in an X-linked recessive pattern.  Duplication of the PLP1 gene is more common than point mutations.  The signs and symptoms are not diagnostic of PMD as mutations in other genes can cause a similar phenotype. 

Spastic paraplegia-2 (SPG2; 312920)is an allelic disorder in which nystagmus and optic atrophy are also found in some patients.

Treatment Options: 

There is no effective treatment for this disease.  Airway protection and seizure control should be applied in specific situations.  Patients often need a feeding tube for adequate nutrition.

Article Title: 


Inoue K. PLP1-related inherited dysmyelinating disorders: Pelizaeus-Merzbacher disease and spastic paraplegia type 2. Neurogenetics. 2005 Feb;6(1):1-16. Review.

PubMedID: 15627202

Gow A, Lazzarini RA. A cellular mechanism governing the severity of Pelizaeus-Merzbacher disease. Nat Genet. 1996 Aug;13(4):422-8.

PubMedID: 8696336

Boespflug-Tanguy O, Mimault C, Melki J, Cavagna A, Giraud G, Pham Dinh D, Dastugue B, Dautigny A. Genetic homogeneity of Pelizaeus-Merzbacher disease: tight linkage to the proteolipoprotein locus in 16 affected families. PMD Clinical Group. Am J Hum Genet. 1994 Sep;55(3):461-7.

PubMedID: 7915877