Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Ver. Summary Created by Modification Content Size Created at Operation
1 + 475 word(s) 475 2020-12-15 07:29:55

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Xu, C. Lissencephaly with Cerebellar Hypoplasia. Encyclopedia. Available online: (accessed on 01 December 2023).
Xu C. Lissencephaly with Cerebellar Hypoplasia. Encyclopedia. Available at: Accessed December 01, 2023.
Xu, Camila. "Lissencephaly with Cerebellar Hypoplasia" Encyclopedia, (accessed December 01, 2023).
Xu, C.(2020, December 24). Lissencephaly with Cerebellar Hypoplasia. In Encyclopedia.
Xu, Camila. "Lissencephaly with Cerebellar Hypoplasia." Encyclopedia. Web. 24 December, 2020.
Lissencephaly with Cerebellar Hypoplasia

Lissencephaly with cerebellar hypoplasia (LCH) affects brain development, resulting in the brain having a smooth appearance (lissencephaly) instead of its normal folds and grooves. In addition, the part of the brain that coordinates movement is unusually small and underdeveloped (cerebellar hypoplasia). Other parts of the brain are also often underdeveloped in LCH, including the hippocampus, which plays a role in learning and memory, and the part of the brain that is connected to the spinal cord (the brainstem).

genetic conditions

1. Introduction

Individuals with LCH have moderate to severe intellectual disability and delayed development. They have few or no communication skills, extremely poor muscle tone (hypotonia), problems with coordination and balance (ataxia), and difficulty sitting or standing without support. Most affected children experience recurrent seizures (epilepsy) that begin within the first months of life. Some affected individuals have nearsightedness (myopia), involuntary eye movements (nystagmus), or puffiness or swelling caused by a buildup of fluids in the body's tissues (lymphedema).

2. Frequency

LCH is a rare condition, although its prevalence is unknown.

3. Causes

LCH can be caused by mutations in the RELN or TUBA1A gene. The RELN gene provides instructions for making a protein called reelin. In the developing brain, reelin turns on (activates) a signaling pathway that triggers nerve cells (neurons) to migrate to their proper locations. The protein produced from the TUBA1A gene is also involved in neuronal migration as a component of cell structures called microtubules. Microtubules are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules form scaffolding within the cell that elongates in a specific direction, altering the cytoskeleton and moving neurons.

Mutations in either the RELN or TUBA1A gene impair the normal migration of neurons during fetal development. As a result, neurons are disorganized, the normal folds and grooves of the brain do not form, and brain structures do not develop properly. This impairment of brain development leads to the neurological problems characteristic of LCH.

4. Inheritance

When LCH is caused by mutations in the RELN gene, the condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

When LCH is caused by mutations in the TUBA1A gene, the condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most of these cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

5. Other Names for This Condition

  • LCH

  • LIS2

  • LIS3

  • lissencephaly 2

  • lissencephaly 3

  • lissencephaly syndrome, Norman-Roberts type

  • Norman-Roberts syndrome


  1. Chang BS, Duzcan F, Kim S, Cinbis M, Aggarwal A, Apse KA, Ozdel O, Atmaca M,Zencir S, Bagci H, Walsh CA. The role of RELN in lissencephaly andneuropsychiatric disease. Am J Med Genet B Neuropsychiatr Genet. 2007 Jan5;144B(1):58-63.
  2. Gressens P. Pathogenesis of migration disorders. Curr Opin Neurol. 2006Apr;19(2):135-40. Review.
  3. Hong SE, Shugart YY, Huang DT, Shahwan SA, Grant PE, Hourihane JO, Martin ND, Walsh CA. Autosomal recessive lissencephaly with cerebellar hypoplasia isassociated with human RELN mutations. Nat Genet. 2000 Sep;26(1):93-6. Erratum in:Nat Genet 2001 Feb;27(2):225.
  4. Kumar RA, Pilz DT, Babatz TD, Cushion TD, Harvey K, Topf M, Yates L, Robb S,Uyanik G, Mancini GM, Rees MI, Harvey RJ, Dobyns WB. TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronalmigration pathways converge on alpha tubulins. Hum Mol Genet. 2010 Jul15;19(14):2817-27. doi: 10.1093/hmg/ddq182.
  5. Ross ME, Swanson K, Dobyns WB. Lissencephaly with cerebellar hypoplasia (LCH):a heterogeneous group of cortical malformations. Neuropediatrics. 2001Oct;32(5):256-63.
  6. Zaki M, Shehab M, El-Aleem AA, Abdel-Salam G, Koeller HB, Ilkin Y, Ross ME,Dobyns WB, Gleeson JG. Identification of a novel recessive RELN mutation using a homozygous balanced reciprocal translocation. Am J Med Genet A. 2007 May1;143A(9):939-44.
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to :
View Times: 200
Entry Collection: MedlinePlus
Revision: 1 time (View History)
Update Date: 24 Dec 2020