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Cerebral dysmyelination

MedGen UID:
Concept ID:
Synonyms: Areas of dysmyelination on MRI; Dysmyelination of the brain
HPO: HP:0007266


Defective structure and function of myelin sheaths of the white matter of the brain. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Cerebral dysmyelination

Conditions with this feature

Pelizaeus-Merzbacher disease
MedGen UID:
Concept ID:
Disease or Syndrome
PLP1 disorders of central nervous system myelin formation include a range of phenotypes from Pelizaeus-Merzbacher disease (PMD) to spastic paraplegia 2 (SPG2). PMD typically manifests in infancy or early childhood with nystagmus, hypotonia, and cognitive impairment; the findings progress to severe spasticity and ataxia. Life span is shortened. SPG2 manifests as spastic paraparesis with or without CNS involvement and usually normal life span. Intrafamilial variation of phenotypes can be observed, but the signs are usually fairly consistent within families. Heterozygous females may manifest mild-to-moderate signs of the disease.
Mucolipidosis type IV
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Concept ID:
Disease or Syndrome
Mucolipidosis IV (MLIV) is an ultra-rare lysosomal storage disorder characterized by severe psychomotor delay, progressive visual impairment, and achlorhydria. Individuals with MLIV typically present by the end of the first year of life with delayed developmental milestones (due to a developmental brain abnormality) and impaired vision (resulting from a combination of corneal clouding and retinal degeneration). By adolescence, all individuals with MLIV have severe visual impairment. A neurodegenerative component of MLIV has become more widely appreciated, with the majority of individuals demonstrating progressive spastic quadriparesis and loss of psychomotor skills starting in the second decade of life. About 5% of individuals have atypical MLIV, manifesting with less severe psychomotor impairment, but still exhibiting progressive retinal degeneration and achlorhydria.
Bifunctional peroxisomal enzyme deficiency
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Concept ID:
Pathologic Function
D-bifunctional protein deficiency is a disorder of peroxisomal fatty acid beta-oxidation. See also peroxisomal acyl-CoA oxidase deficiency (264470), caused by mutation in the ACOX1 gene (609751) on chromosome 17q25. The clinical manifestations of these 2 deficiencies are similar to those of disorders of peroxisomal assembly, including X-linked adrenoleukodystrophy (ALD; 300100), Zellweger cerebrohepatorenal syndrome (see 214100) and neonatal adrenoleukodystrophy (NALD; see 601539) (Watkins et al., 1995). DBP deficiency has been classified into 3 subtypes depending upon the deficient enzyme activity. Type I is a deficiency of both 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase; type II is a deficiency of hydratase activity alone; and type III is a deficiency of dehydrogenase activity alone. Virtually all patients with types I, II, and III have a severe phenotype characterized by infantile-onset of hypotonia, seizures, and abnormal facial features, and most die before age 2 years. McMillan et al. (2012) proposed a type IV deficiency on the basis of less severe features; these patients have a phenotype reminiscent of Perrault syndrome (PRLTS1; 233400). Pierce et al. (2010) noted that Perrault syndrome and DBP deficiency overlap clinically and suggested that DBP deficiency may be underdiagnosed.
PCWH syndrome
MedGen UID:
Concept ID:
Disease or Syndrome
PCWH syndrome is a complex neurocristopathy that includes features of 4 distinct syndromes: peripheral demyelinating neuropathy (see 118200), central dysmyelination, Waardenburg syndrome, and Hirschsprung disease (see 142623) (Inoue et al., 2004). Inoue et al. (2004) proposed the acronym PCWH for this disorder.
Bilateral frontoparietal polymicrogyria
MedGen UID:
Concept ID:
Disease or Syndrome
Complex cortical dysplasia with other brain malformations-14A (CDCBM14A) is an autosomal recessive neurologic disorder characterized by global developmental delay with impaired intellectual development, motor delay, poor speech development, and early-onset seizures, often focal or atypical absence. Additional features may include strabismus, nystagmus, exo- or esotropia, axial hypotonia, and spasticity. Brain imaging shows bilateral frontoparietal polymicrogyria, a frontal-predominant cobblestone malformation of the cortex, scalloping of the cortical/white matter junction, enlarged ventricles, and hypoplasia of the pons, brainstem, and cerebellum. The disorder can be classified as a malformation of cortical development (summary by Parrini et al., 2009; Luo et al., 2011; Zulfiqar et al., 2021). For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039).
Megalencephaly with dysmyelination
MedGen UID:
Concept ID:
Disease or Syndrome
PHGDH deficiency
MedGen UID:
Concept ID:
Disease or Syndrome
Phosphoglycerate dehydrogenase deficiency (PHGDHD) is an autosomal recessive inborn error of L-serine biosynthesis that is characterized by congenital microcephaly, psychomotor retardation, and seizures (summary by Jaeken et al., 1996).
Krabbe disease due to saposin A deficiency
MedGen UID:
Concept ID:
Disease or Syndrome
Adducted thumbs-arthrogryposis syndrome, Christian type
MedGen UID:
Concept ID:
Disease or Syndrome
A type of arthrogryposis with characteristics of congenital cleft palate, microcephaly, craniostenosis and arthrogryposis. Additional features include facial dysmorphism. Velopharyngeal insufficiency with difficulties in swallowing, increased secretion of the nose and throat, prominent occiput, generalised muscular hypotonia with mild cyanosis and no spontaneous movements, seizures, torticollis, areflexia, intellectual disability, hypertrichosis of the lower extremities, and scleroedema are also observed. The disease often leads to early death. Transmission is autosomal recessive. No new cases have been described since 1983.

Professional guidelines


Gilbert EAB, Livingston J, Flores EG, Khan M, Kandavel H, Morshead CM
Brain Res 2024 Jan 1;1822:148648. Epub 2023 Oct 26 doi: 10.1016/j.brainres.2023.148648. PMID: 37890574
Mifsud G, Zammit C, Muscat R, Di Giovanni G, Valentino M
CNS Neurosci Ther 2014 Jul;20(7):603-12. Epub 2014 Apr 7 doi: 10.1111/cns.12263. PMID: 24703424Free PMC Article
Goldman SA
Arch Neurol 2011 Jul;68(7):848-56. Epub 2011 Mar 14 doi: 10.1001/archneurol.2011.46. PMID: 21403006Free PMC Article

Recent clinical studies


Netzer C, Helmstaedter C, Ehrbrecht A, Engels H, Schwanitz G, Urbach H, Schröder R, Weber RG, Kornblum C
Acta Neurol Scand 2006 Aug;114(2):133-8. doi: 10.1111/j.1600-0404.2006.00626.x. PMID: 16867037

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