Pelizaeus-Merzbacher disease, connatal form

MedGen UID:: 1842817
•Concept ID:: C5679776
•: Disease or Syndrome

Synonyms:	Connatal PMD; connatal PMD; Pelizaeus-Merzbacher disease type II; severe PMD; Severe PMD
Modes of inheritance:	X-linked recessive inheritance MedGen UID: 375779 •Concept ID: C1845977 • Finding Source: Orphanet A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele. See: This record X-linked recessive inheritance (Orphanet)

Monarch Initiative:	MONDO:0017221
Orphanet:	ORPHA280210

Definition

The connatal form of Pelizaeus-Merzbacher disease (PMD) is the most severe form of PMD (see this term). [from ORDO]

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVPelizaeus-Merzbacher disease, connatal form

Disease
- Non-Neoplastic Disorder
  - Non-Neoplastic Disorder by Special Category
    - Degenerative disorder
      - Degenerative disease of the central nervous system
        Pelizaeus-Merzbacher disease
        Pelizaeus-Merzbacher disease, connatal form

Recent clinical studies

Etiology

Hereditary spastic paraplegia caused by the PLP1 'rumpshaker mutation'.

Svenstrup K, Giraud G, Boespflug-Tanguy O, Danielsen ER, Thomsen C, Rasmussen K, Law I, Vogel A, Stokholm J, Crone C, Hjermind LE, Nielsen JE
J Neurol Neurosurg Psychiatry 2010 Jun;81(6):666-72. Epub 2009 Dec 1 doi: 10.1136/jnnp.2009.180315. PMID: 19955111

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Diagnosis

Pelizaeus-Merzbacher disease in patients with molecularly confirmed diagnosis.

Mierzewska H, Jamroz E, Mazurczak T, Hoffman-Zacharska D, Szczepanik E
Folia Neuropathol 2016;54(1):59-65. doi: 10.5114/fn.2016.58916. PMID: 27179222

The spectrum of PLP1 gene mutations in patients with the classical form of the Pelizaeus-Merzbacher disease.

Hoffman-Zacharska D, Mierzewska H, Szczepanik E, Poznański J, Mazurczak T, Jakubiuk-Tomaszuk A, Mądry J, Kierdaszuk A, Bal J
Med Wieku Rozwoj 2013 Oct-Dec;17(4):293-300. PMID: 24519770

The molecular and cellular defects underlying Pelizaeus-Merzbacher disease.

Woodward KJ
Expert Rev Mol Med 2008 May 19;10:e14. doi: 10.1017/S1462399408000677. PMID: 18485258

Neurophysiologic studies and MRI in Pelizaeus-Merzbacher disease: comparison of classic and connatal forms.

Wang PJ, Young C, Liu HM, Chang YC, Shen YZ
Pediatr Neurol 1995 Jan;12(1):47-53. doi: 10.1016/0887-8994(94)00124-k. PMID: 7748360

Pelizaeus-Merzbacher disease: classical or connatal?

Scheffer IE, Baraitser M, Wilson J, Harding B, Kendall B, Brett EM
Neuropediatrics 1991 May;22(2):71-8. doi: 10.1055/s-2008-1071420. PMID: 1857497

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Prognosis

Inherited white matter disorders: Hypomyelination (myelin disorders).

Perrier S, Gauquelin L, Bernard G
Handb Clin Neurol 2024;204:197-223. doi: 10.1016/B978-0-323-99209-1.00014-4. PMID: 39322379

Pelizaeus-Merzbacher disease in patients with molecularly confirmed diagnosis.

Mierzewska H, Jamroz E, Mazurczak T, Hoffman-Zacharska D, Szczepanik E
Folia Neuropathol 2016;54(1):59-65. doi: 10.5114/fn.2016.58916. PMID: 27179222

The spectrum of PLP1 gene mutations in patients with the classical form of the Pelizaeus-Merzbacher disease.

Hoffman-Zacharska D, Mierzewska H, Szczepanik E, Poznański J, Mazurczak T, Jakubiuk-Tomaszuk A, Mądry J, Kierdaszuk A, Bal J
Med Wieku Rozwoj 2013 Oct-Dec;17(4):293-300. PMID: 24519770

Pelizaeus-Merzbacher disease: classical or connatal?

Scheffer IE, Baraitser M, Wilson J, Harding B, Kendall B, Brett EM
Neuropediatrics 1991 May;22(2):71-8. doi: 10.1055/s-2008-1071420. PMID: 1857497

Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein.

Gencic S, Abuelo D, Ambler M, Hudson LD
Am J Hum Genet 1989 Sep;45(3):435-42. PMID: 2773936 Free PMC Article

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Clinical prediction guides

Characterization of a PLP-overexpressing transgenic rat, a model for the connatal form of Pelizaeus-Merzbacher disease.

Mayer JA, Larsen EC, Kondo Y, Duncan ID
Neurobiol Dis 2011 Nov;44(2):231-8. Epub 2011 Jul 18 doi: 10.1016/j.nbd.2011.07.007. PMID: 21784154

Proton MR spectroscopic imaging in Pelizaeus-Merzbacher disease.

Pizzini F, Fatemi AS, Barker PB, Nagae-Poetscher LM, Horská A, Zimmerman AW, Moser HW, Bibat G, Naidu S
AJNR Am J Neuroradiol 2003 Sep;24(8):1683-9. PMID: 13679292 Free PMC Article

A severe connatal form of Pelizaeus Merzbacher disease in a Czech boy caused by a novel mutation (725C>A, Ala242Glu) at the 'jimpy(msd) codon' in the PLP gene.

Seeman P, Paderova K, Benes V Jr, Sistermans EA
Int J Mol Med 2002 Feb;9(2):125-9. PMID: 11786921

Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein.

Gencic S, Abuelo D, Ambler M, Hudson LD
Am J Hum Genet 1989 Sep;45(3):435-42. PMID: 2773936 Free PMC Article

Seitelberger's connatal form of Pelizaeus-Merzbacher Disease. Case report, clinical, pathological and biochemical findings.

Ulrich J, Herschkowitz N
Acta Neuropathol 1977 Oct 10;40(2):129-36. doi: 10.1007/BF00688701. PMID: 201145

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