Lissencephaly Treatment

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  • What is Lissencephaly?
  • Causes of Lissencephaly
  • Treatment of Lissencephaly

What is Lissencephaly?

Lissencephaly is a condition that causes the cerebral cortex of the brain to become abnormally smooth, which results in a multitude of symptoms including facial malformations and even seizures. Treatment options aim to manage the symptoms of the condition as there is no cure.

Lissencephaly is a group of disorders that are caused by malfunctions in the brain development of a fetus. There are two types of lissencephaly, classic lissencephaly (type 1) and cobblestone complex (type 2). Both types have a different pathogenesis.

The main types of classic lissencephaly are isolated lissencephaly sequence (ILS) and Miller-Dieker syndrome (MDS).  ILS is a disorder consisting of severe lissencephaly with no other malformations, whereas MDS consists of more severe lissencephaly than ILS patients, other facial abnormalities (e.g. high forehead, small nose, and small jaw), and other non-facial malformations. X-linked forms of lissencephaly also exist.

Common symptoms of lissencephaly include an unusual facial structure, a difficulty swallowing, muscle spasms, seizures, and psychomotor retardation. The expression of these symptoms varies greatly between individuals, as the severity of the condition depends on the amount of brain malformation that has occurred. Some children have almost normal development, whereas some don’t survive past 5 months. The most common causes of early death with this condition are respiratory disease or severe seizures.

Causes of Lissencephaly

In the U.S, approximately 1 in 100,000 babies are born with lissencephaly. Research has shown that several different genes contribute to the development of lissencephaly which is a testament to the varied expression seen between different children with the disease.

Research has also shown that current knowledge regarding the genetic and hereditary causes of the disease are not very well understood, as children with the disease may have no changes in the genes that are connected to the disease. This eludes to the fact that there are other ‘undiscovered’ genes that contribute to the disease.

Two main genes have been identified to directly cause lissencephaly. LIS1 is disrupted/mutated in ILS and MDS patients, and Doublecortin (DCX) is mutated in the X-linked forms of lissencephaly.

Treatment of Lissencephaly

Diagnosing lissencephaly is typically done using brain scans (such as a CT scans, MRI, or EEG), following a diagnosis, genetic testing can be performed with the aim to find a mutation that caused the condition.

There is currently no cure for lissencephaly and the treatment options available involve managing the symptoms of the condition. Fortunately, many children that survive past 5-months show natural progress in their development over time. Seizures can be managed using anti-convulsant medications. A gastrostomy tube can also be used to help infants that struggle with feeding.

Current research on mice models has given important insights into the development of more treatment options for lissencephaly. One study applied a blood-brain barrier permeable calpain inhibitor – SNJ1945 – to mice with lissencephaly (LIS1+/- variants).

Both peri-natal and post-natal treatments were effective at rescuing the defective neuronal migration and helped to improve the behavioral performance of the mice. ALLN e64d is another calpain inhibitor that was tested in a different study. This study found that although the mice still showed defects of the hippocampus cells, they were drastically improved compared to the mice without treatment. These results suggest that calpain inhibitors may be a potential therapy for the treatment of lissencephaly.

Genetically modified mice with DCX knockdowns had abnormally positioned neurons stimulated to migrate by re-expressing DCX. This migration reduces neocortical malformations and restores functional neuronal patterning, suggesting that conditions arising from DCX mutations may be able to be treated using similar methods in the future.


  • Mochida, G. (2009). Genetics and Biology of Microcephaly and Lissencephaly. Seminars in Pediatric Neurology.
  • Toba, S., et al. (2013). Post-natal treatment by a blood-brain-barrier permeable calpain inhibitor, SNJ1945 rescued defective function in lissencephaly. Scientific Reports.
  • Wynshaw-Boris, A., et al. (2010). Lissencephaly: Mechanistic insights from animal models and potential therapeutic strategies. Seminars in Cell & Developmental Biology.
  • National institute of Neurological Disorders and Strokes. Lissencephaly information page. (2019).…/Lissencephaly-Information-Page

Further Reading

  • All Lissencephaly Content
  • Lissencephaly – What is Lissencephaly?
  • Lissencephaly Symptoms
  • Lissencephaly Types

Last Updated: May 22, 2019

Written by

Samuel Mckenzie

Sam graduated from the University of Manchester with a B.Sc. (Hons) in Biomedical Sciences. He has experience in a wide range of life science topics, including; Biochemistry, Molecular Biology, Anatomy and Physiology, Developmental Biology, Cell Biology, Immunology, Neurology  and  Genetics.

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