Lissencephaly type I - subcortical band heterotopia spectrum

A.Prof Frank Gaillard et al.

Lissencephaly type I, also known as classic lissencephaly, is a heterogeneous group of disorders of cortical formation characterised by a smooth brain, with absent or hypoplastic sulci and is strongly associated with subcortical band heterotopia (see classification system for cortical malformations) and therefore the term lissencephaly type I - subcortical band heterotopia spectrum is probably a better choice.

This article focuses on the lissencephaly end of the lissencephaly - subcortical band heterotopia spectrum. For further discussion refer to the articles on lissencephaly (general overview) and band heterotopia

  • content pending

In all forms of type I lissencephaly, infants present with marked hypotonia and paucity of movement and difficulty feeding. Although often these children have head circumference within normal limits at birth, head growth is slow, and most have microcephaly by one year of age 1,4

Seizures are also a prominent feature, becoming apparent in 90% of children before the age of 6 months, usually initially in the form of infantile spasms (West syndrome). Later they progress to Lennox-Gastaut syndrome 4

Type I lissencephaly results from any one of at least 5 (perhaps more) mutations 1,4-5:

  • isolated: without a known genetic defect
  • PAFAH1B1 (LIS1) gene mutation
  • doublecortin (DCX) gene mutation
    • presents as lissencephaly usually in males
    • presents as subcortical band heterotopia (double cortex) usually in females 4-5
  • XLAG
  • RELN

Histological examination of the cortex reveals only 4 poorly organized layers (rather than the normal 6) 4:  

  1. marginal zone: poorly defined with increased cellularity
  2. superficial cortical gray zone with diffusely scattered neurons
  3. relatively neuron-sparse zone
  4. deep cortical gray zone with neurons often oriented in columns

Although morphological changes are visible on all modalities able to image the brain (antenatal and perinatal ultrasound, CT and MRI), MRI is the modality of choice in assessing the changes of lissencephaly. 

MRI

The brain is usually grossly abnormal in outline, with only a few shallow sulci and shallow Sylvian fissures, taking on an hour glass or figure-8 appearance on axial imaging. The cortex is markedly thickened measuring 12-20mm (rather than the normal 3-4mm) 6. Subcortical band heterotopia is also sometimes visible.

The subcortical heterotopia is usually diffuse and symmetric but sometimes an anterior-posterior predilection is present which suggests a specific underlying genetic abnormality 4

  • anterior predilection suggests mutations of DCX
  • posterior predilection suggests mutations of LIS1

Additional features usually also present include 4:

In both isolated lissencephaly or Miller-Dieker syndrome (MDS) developmental prognosis is poor, with individuals never achieving a developmental equivalent than 3-5 months age. 

To make matters worse, epilepsy in these individuals is usually difficult to control. 

Regarding actual survival, the prognosis is worse for children with Miller-Dieker syndrome (MDS), with most succumbing (most frequently to aspiration pneumonia) within the first two years of life. In children with isolated lissencephaly survival is somewhat better with approximately half of individuals reaching 10 years of age, but most dying before the end of adolescence 4.  

Malformations of the central nervous system
Share article

Article information

rID: 16168
Section: Pathology
Synonyms or Alternate Spellings:
  • Type I lissencephaly
  • Classic lissencephaly
  • Lissencephaly type I

Support Radiopaedia and see fewer ads

Cases and figures

  • Drag
    Inversion recovery
    Case 1
    Drag here to reorder.
  • Drag
    Lissencephaly
    Case 2
    Drag here to reorder.
  • Drag
    Case 3
    Drag here to reorder.
  • Updating… Please wait.
    Loadinganimation

    Alert accept

    Error Unable to process the form. Check for errors and try again.

    Alert accept Thank you for updating your details.