Pelizaeus-Merzbacher-Like Disease (PMLD) FAQS

 

What is PMLD and what are its symptoms?

Pelizaeus-Merzbacher-Like Disease, or PMLD, is a slowly progressive disease of myelin, which is the white matter of the central nervous system (brain and spinal cord).

In patients with PMLD, the myelin does not form properly. Myelin insulates the nerves for proper conduction of nerve impulses. When the myelin does not form properly, nerve impulses do not travel properly in the central nervous system

The symptoms of PMLD are: weak muscle tone (hypotonia), involuntary movements of the eyes (nystagmus), and delayed development of speech and motor skills, such as sitting or grasping objects, and muscle stiffness (spasticity), which replaces hypotonia as children get older.

For more informationon PMLD, see PubMed.gov - Pelizaeus-Merzbacher-Like Disease 1 and NIH National Library of Medicine - Genetics Home Reference.

 

What is Myelin?

 

Myelin is the fatty substance that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses are passed along the axon.

 

How is PMLD similar and Different from PMD?

Pelizaeus-Merzbacher Disease (PMD) is a X-linked disorder caused by a variant in the PLP1 gene expressing proteolipid protein. The symptoms are similar to those in PMLD (nystagmus, hypotonia, global development delay, progressing later to ataxia and severe spasticity). 

Pelizaeus-Merzbacher-Like Disease (PMLD) is caused by mutations in the GJC2 gene, expressing the connexin 47 protein, responsible for communication channels between nervous system cells, which affects myelin formation in the central nervous system.

For more information, see PubMed.gov - Pelizaeus-Merzbacher-Like Disease 1.

 

What Causes PMLD?

Pelizaeus-Merzbacher-Like Disease type 1 is caused by mutations in the GJC2 gene. This gene provides instructions for making a protein called connexin-47. This protein plays a role in forming channels called gap junctions between cells. Gap junctions made with connexin-47 facilitate communication between nervous system cells, which is necessary for the formation of myelin.

For more information, see Genetics Home Reference - Pelizaeus-Merzbacher-Like Disease - Definition. 

To better understand types of gene mutations see MedlinePlus - What kinds of gene mutations are possible?

 

What is the Prevalence (Frequency) of PMLD?

The prevalence of Pelizaeus-Merzbacher-Like Disease type 1 is unknown, but it is thought to be rare.

Source: Genetics Home Reference - Pelizaeus-Merzbacher-Like Disease - Definition

 

What Are the Different Names of PMLD?

  • HLD2

  • hypomyelinating leukodystrophy 2

  • Pelizaeus Merzbacher Like Disease

  • Pelizaeus-Merzbacher-Like Disease

  • PMLD - Pelizaeus Merzbacher Like Disease

  • PMLD1

Source: Genetics Home Reference - Pelizaeus-Merzbacher-Like Disease - Definition 

 

What are the Different Names for the GJC2 Gene?

  • GJC2

  • connexin-46.6

  • connexin-47

  • CX46.6

  • Cx47

  • gap junction alpha-12 protein

  • gap junction gamma-2 protein

  • gap junction protein, gamma 2, 47kDa

  • GJA12

Source: Genetics Home Reference - Pelizaeus-Merzbacher-Like Disease - Definition

 

Is There a Cure or Treatments for PMLD?

Currently, there are treatments for some of the symptoms of PMLD, such as drugs that reduce spasticity, but there is no known cure. 

For more information, see PubMed.gov - Pelizaeus-Merzbacher-Like Disease 1. 


How Do I Find Help for My Child?

You can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. 

For more information, see NIH - Genetic and Rare Diseases Information Center - How to Find a Disease Specialist. 


How is PMLD Inherited? 

PMD1 PMLD is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Source: MedlinePlus, National Library of Medicine.

For more information, see PubMed.gov - Pelizaeus-Merzbacher-Like Disease 1 - Genetic Counseling.

Are There Other Syndromes with Similar Symptoms to PMLD?

In brief, other syndromes have also been referred to as PMLD but their inclusion as PMLD has been debated because of their severity and of the evidence of neuronal in addition to white matter , besides white matter, involvement on MRI.

For more information, see PubMed.gov - Pelizaeus-Merzbacher-Like Disease 1 - Differential Diagnosis.