eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases

Pelizaeus-Merzbacher Disease: Follow-up

Author: James Y Garbern, MD, PhD, Clinical Director of Neurogenetics Clinic, Associate Professor, Department of Neurology and Center for Molecular Medicine and Genetics, Detroit Medical Center, Wayne State University School of Medicine
Contributor Information and Disclosures

Updated: Aug 22, 2008

Follow-up

Further Outpatient Care

  • Regular consultation with a physiatrist or orthopedist and therapy team should be arranged.
  • Referral to a geneticist or genetic counselor, reproductive geneticist, or both should be arranged when a family wants additional children.

Inpatient & Outpatient Medications

  • When indicated, antiepileptic medications should be used. Antispasticity medications such as baclofen, tizanidine, or benzodiazepines may be beneficial.
  • Constipation is a common complication and may require use of mild laxatives, such as senna, fiber supplements, or osmotic agents such as polyethylene glycol 3350 (MiraLax, Enemeez).

Deterrence/Prevention

  • Families who plan to have additional children should be referred to a geneticist and reproductive geneticist.

Complications

  • Respiratory difficulty and stridor can be severe enough in infants with connatal disease that tracheostomy or other airway protection may be needed. As the child grows older, the need for this may lessen.
  • Orthopedic complications are common in Pelizaeus-Merzbacher disease (PMD). Joint contractures are common in the legs and, to a lesser extent, in the arms. Scoliosis can be severe enough to cause restrictive lung disease. Regular physical medicine evaluations, bracing, and physical therapy, as well as other treatments for spasticity may reduce or delay the need for surgical therapy.
  • Dysphagia can be severe enough to necessitate consideration of feeding tube placement.

Prognosis

  • Individuals with connatal Pelizaeus-Merzbacher disease typically die of respiratory complications during childhood, but with attentive care, they can live into the third decade of life.
  • Those with classic Pelizaeus-Merzbacher disease can live into the fifth to sixth decades of life.
  • Patients with a predominantly spastic paraplegia phenotype have a normal life span and may even reproduce.
  • Each form of the disease may have real or apparent intervals of stability, but overall the trend is of gradual progression.
  • Heterozygous females who carry a severe mutation are usually healthy, but those who carry a relatively mild mutation may develop neurologic signs, including spastic paraparesis and dementia, that typically manifest during adulthood.

Patient Education

Miscellaneous

Medicolegal Pitfalls

  • Failure to recognize the disease in a child who has no family history of Pelizaeus-Merzbacher disease (PMD) or failure to refer the parents of a child with Pelizaeus-Merzbacher disease to an appropriate genetics specialist may result in the parents having an avoidable pregnancy with another affected child ("wrongful birth").
  • Neglect of proper physical therapy, seating, and exercise needs predisposes to orthopedic complications that may lead to severe discomfort and respiratory compromise.

Special Concerns

  • As a hereditary disorder, Pelizaeus-Merzbacher disease affects the lives not only of the affected individuals but also their relatives.
  • Competent genetic counseling must be provided to the family of an affected individual to provide the most accurate prognosis for the individual and to educate the family about implications for future pregnancies.
  • Prenatal testing and preimplantation genetic testing are both possible and should be offered when appropriate.
 
Acknowledgments

The author is extremely grateful to patients with Pelizaeus-Merzbacher disease and their families for their help and support of Pelizaeus-Merzbacher disease research and to the Pelizaeus-Merzbacher disease foundation, the National Institutes of Health, and the Children's Research Center of Michigan for financial support.



More on Pelizaeus-Merzbacher Disease

Overview: Pelizaeus-Merzbacher Disease
Differential Diagnoses & Workup: Pelizaeus-Merzbacher Disease
Treatment & Medication: Pelizaeus-Merzbacher Disease
Follow-up: Pelizaeus-Merzbacher Disease
Multimedia: Pelizaeus-Merzbacher Disease
References
[ CLOSE WINDOW ]

References

  1. van der Knaap MS, Smit LM, Barth PG, et al. Magnetic resonance imaging in classification of congenital muscular dystrophies with brain abnormalities. Ann Neurol. Jul 1997;42(1):50-9. [Medline].

  2. Griffiths I, Klugmann M, Anderson T, et al. Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science. Jun 5 1998;280(5369):1610-3. [Medline].

  3. Wolf NI, Sistermans EA, Cundall M, et al. Three or more copies of the proteolipid protein gene PLP1 cause severe Pelizaeus-Merzbacher disease. Brain. Apr 2005;128(Pt 4):743-51. [Medline].

  4. Lazzarini A, Schwarz KO, Jiang S, et al. Pelizaeus-Merzbacher-like disease: exclusion of the proteolipid protein locus and documentation of a new locus on Xq. Neurology. Sep 1997;49(3):824-32. [Medline].

  5. Aicardi J. The inherited leukodystrophies: a clinical overview. J Inherit Metab Dis. 1993;16(4):733-43. [Medline].

  6. Barkovich AJ. Magnetic resonance techniques in the assessment of myelin and myelination. J Inherit Metab Dis. 2005;28(3):311-43. [Medline].

  7. Barkovich AJ, Ferriero DM, Bass N, Boyer R. Involvement of the pontomedullary corticospinal tracts: a useful finding in the diagnosis of X-linked adrenoleukodystrophy. AJNR Am J Neuroradiol. Jan 1997;18(1):95-100. [Medline].

  8. Boulloche J, Aicardi J. Pelizaeus-Merzbacher disease: clinical and nosological study. J Child Neurol. Jul 1986;1(3):233-9. [Medline].

  9. Garbern J, Krajewski KM, Hobson GM. PLP1-related disorders. Geneclinics. Available at http://www.geneclinics.org/profiles/pmd. Accessed 2006.

  10. Garbern JY. Pelizaeus-Merzbacher disease: Genetic and cellular pathogenesis. Cell Mol Life Sci. 2007;64:50-65. [Medline]. [Full Text].

  11. Garbern JY, Yool DA, Moore GJ, et al. Patients lacking the major CNS myelin protein, proteolipid protein 1, develop length-dependent axonal degeneration in the absence of demyelination and inflammation. Brain. Mar 2002;125(Pt 3):551-61. [Medline].

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

  13. Griffiths I, Klugmann M, Anderson T, et al. Current concepts of PLP and its role in the nervous system. Microsc Res Tech. Jun 1 1998;41(5):344-58. [Medline].

  14. Hodes ME, DeMyer WE, Pratt VM, et al. Girl with signs of Pelizaeus-Merzbacher disease heterozygous for a mutation in exon 2 of the proteolipid protein gene. Am J Med Genet. Feb 13 1995;55(4):397-401. [Medline].

  15. Hodes ME, Woodward K, Spinner NB, et al. Additional copies of the proteolipid protein gene causing Pelizaeus-Merzbacher disease arise by separate integration into the X chromosome. Am J Hum Genet. Jul 2000;67(1):14-22. [Medline].

  16. Hurst S, Garbern J, Trepanier A, Gow A. Quantifying the carrier female phenotype in Pelizaeus-Merzbacher disease. Genet Med. Jun 2006;8(6):371-8. [Medline].

  17. Inoue K, Osaka H, Imaizumi K, et al. Proteolipid protein gene duplications causing Pelizaeus-Merzbacher disease: molecular mechanism and phenotypic manifestations. Ann Neurol. May 1999;45(5):624-32. [Medline].

  18. Inoue K, Tanabe Y, Lupski JR. Myelin deficiencies in both the central and the peripheral nervous systems associated with a SOX10 mutation. Ann Neurol. Sep 1999;46(3):313-8. [Medline].

  19. Jouet M, Rosenthal A, Armstrong G, et al. X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene. Nat Genet. Jul 1994;7(3):402-7. [Medline].

  20. Kim TS, Kim IO, Kim WS, et al. MR of childhood metachromatic leukodystrophy. AJNR Am J Neuroradiol. Apr 1997;18(4):733-8. [Medline].

  21. Kremer H, Hamel BC, van den Helm B, et al. Localization of the gene (or genes) for a syndrome with X-linked mental retardation, ataxia, weakness, hearing impairment, loss of vision and a fatal course in early childhood. Hum Genet. Nov 1996;98(5):513-7. [Medline].

  22. Lee JA, Carvalho CM, Lupski JR. A DNA replication mechanism for generating nonrecurrent rearrangements associated with genomic disorders. Cell. 2007;131:1235-47. [Medline]. [Full Text].

  23. Lewis RA, Sumner AJ. The electrodiagnostic distinctions between chronic familial and acquireddemyelinative neuropathies. Neurology. Jun 1982;32(6):592-6. [Medline].

  24. McKusick V. Pelizaeus-Merzbacher disease. Online Mendelian Inheritance in Man. Available at http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=312080. Accessed 2004.

  25. Mimault C, Giraud G, Courtois V, et al. Proteolipoprotein gene analysis in 82 patients with sporadic Pelizaeus-Merzbacher Disease: duplications, the major cause of the disease, originate more frequently in male germ cells, but point mutations do not. The Clinical European Network on Brain Dysmyelinating Disease. Am J Hum Genet. Aug 1999;65(2):360-9. [Medline].

  26. Nance MA, Boyadjiev S, Pratt VM, et al. Adult-onset neurodegenerative disorder due to proteolipid protein genemutation in the mother of a man with Pelizaeus-Merzbacher disease. Neurology. Nov 1996;47(5):1333-5. [Medline].

  27. Tanaka M, Hamano S, Sakata H, et al. Discrepancy between auditory brainstem responses, auditory steady-state responses, and auditory behavior in two patients with Pelizaeus-Merzbacher disease. Auris Nasus Larynx. Sep 2008;35(3):404-7. [Medline].

  28. Uhlenberg B, Schuelke M, Rüschendorf F, et al. Mutations in the gene encoding gap junction protein alpha 12 (connexin 46.6) cause Pelizaeus-Merzbacher-like disease. Am J Hum Genet. Aug 2004;75(2):251-60. [Medline]. [Full Text].

  29. Woodward K, Malcolm S. Proteolipid protein gene: Pelizaeus-Merzbacher disease in humans and neurodegeneration in mice. Trends Genet. Apr 1999;15(4):125-8. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Pelizaeus-Merzbacher disease, PMD, spastic paraplegia type 2, SPG2, sudanophilic leukodystrophy, connatal form, proteolipid protein 1, defective CNS myelination, nystagmus, stridor, spastic quadriparesis, hypotonia, cognitive impairment, ataxia, tremor, diffuse leukoencephalopathy, spastic paraplegia syndrome, seizures, spinal muscular atrophy, Salla disease, metachromatic leukodystrophy, adrenoleukodystrophy, Krabbe disease, Cockayne disease, Canavan disease, MASA syndrome, hydrocephalus

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

James Y Garbern, MD, PhD, Clinical Director of Neurogenetics Clinic, Associate Professor, Department of Neurology and Center for Molecular Medicine and Genetics, Detroit Medical Center, Wayne State University School of Medicine
James Y Garbern, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Association for the Advancement of Science, American Society of Human Genetics, and Society for Neuroscience
Disclosure: Nothing to disclose.

Medical Editor

Stephen T Gancher, MD, Adjunct Associate Professor, Department of Neurology, Oregon Health Sciences University
Stephen T Gancher, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, and Movement Disorders Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Nestor Galvez-Jimenez, MD, MSc, MHA, Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida
Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.