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Lissencephaly with cerebellar hypoplasia
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Reviewed August 2013
What is 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).
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).
How common is lissencephaly with cerebellar hypoplasia?
LCH is a rare condition, although its prevalence is unknown.
What genes are related to lissencephaly with cerebellar hypoplasia?
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.
How do people inherit lissencephaly with cerebellar hypoplasia?
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.
Where can I find information about diagnosis or management of lissencephaly with cerebellar hypoplasia?
These resources address the diagnosis or management of lissencephaly with cerebellar hypoplasia and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about lissencephaly with cerebellar hypoplasia?
You may find the following resources about lissencephaly with cerebellar hypoplasia helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for lissencephaly with cerebellar hypoplasia?
What if I still have specific questions about lissencephaly with cerebellar hypoplasia?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding lissencephaly with cerebellar hypoplasia?
ataxia ; autosomal ; autosomal dominant ; autosomal recessive ; cell ; cytoskeleton ; gene ; hypoplasia ; hypotonia ; involuntary ; lymphedema ; muscle tone ; myopia ; nearsightedness ; neurological ; nystagmus ; prevalence ; protein ; recessive ; syndrome
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (6 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.