hypomyelinating disorders

Hypomyelinating disorders are a heterogeneous subset of white matter disorders characterized by abnormally low amounts of myelination.

In distinction to other myelin disorders, hypomyelination is a permanent deficiency in myelin deposition rather than myelin destruction (i.e. demyelination) or abnormal myelin deposition (i.e. dysmyelination).

Clinical presentation

Clinical findings are non-specific but patients often present with developmental delay, cerebellar signs or spasticity. Some disorders have additional clinical findings.

Pathology

The exact pathogenesis varies depending on the exact underlying disorder, but they represent inborn errors of metabolism.

Etiology

They can be etiologically subcategorised into those with and without typical peripheral nervous system involvement (usually based on nerve conduction studies):

• with typical peripheral nervous system involvement
  • hypomyelination with congenital cataract
  • 4H syndrome: hypomyelination, hypogonadotropic hypogonadism, and hypodontia
  • Cockayne syndrome
  • SOX10 (peripheral neuropathy, central hypomyelination, Waardenburg syndrome, Hirschsprung's disease)
• no typical peripheral nervous system involvement
  • Pelizaeus-Merzbacher disease and Pelizaeus-Merzbacher like disease
  • Tay syndrome (trichothiodystrophy with hypersensitivity to sunlight)
  • Salla disease
  • H-ABC (hypomyelination with atrophy of basal ganglia and cerebellum)
  • fucosidosis
  • serine synthesis defects
  • oculogenital dysplasia
  • galactosemia
  • 18q syndrome
  • early onset neuronal degenerative disorders
• others
  • prematurity
  • GM1 gangliosidosis
  • spastic paraplegia type 2

Radiographic features

MRI

The imaging diagnosis of hypomyelination is made on the basis of :

• unchanged myelination pattern not appropriately progressed for the patient's corrected gestational age on two successive brain MRI scans carried out at least 6 months apart
• at least one MRI scan should have been acquired after the age of 12 months

The underlying disorder is usually diagnosed by genetic testing but ancillary MRI features seen in some of these disorders may narrow the differentials for testing.

Please refer to the article on normal myelination for details on MRI assessment of myelination.

Siehe auch:

• Demyelinisierende Erkrankung
• De-Grouchy-Syndrom Typ 2
• white matter disorders
• myelination
• Pelizaeus Merzbacher disease
• dysmyelinating disease

und weiter:

• dysmyelinating disorders