Clinical Characteristics

The clinical features of this disease include:

  • Global developmental delay
  • Developmental regression

Central Nervous System:

  • Reduction in the brain volume (especially of the white matter)
  • Intractable seizures
  • Microcephaly
  • Delayed speech and language development
  • Motor delay
  • Movement abnormalities
  • Ventriculomegaly
  • Absent myelination
  • Hypoplastic corpus callosum
  • Cerebellar hypoplasia
  • Cystic encephalomalacia
  • Hypoplastic optic nerves
  • Hypoplasia of the optic discs
  • Abnormal tracking and focusing
  • Irregular eye movements
  • Cortical blindness
  • EEG abnormalities (e.g. slowing of the background activity, hypsarrhythmia, diffuse delta-subdelta activity, spike waves)
  • Peripheral hypertonia
  • Cerebral palsy
  • Gastroesophageal reflux

Other abnormalities (reported in Dr. Janette Mailo’s patient):

  • Global cerebral atrophy
  • Hypomyelination
  • Axial hypotonia
  • Swallowing difficulties
  • Early thelarche
  • Female hirsutism
  • Increased pipecolic acid

A severe phenotype of the disease usually results in early death.