What is Lissencephaly

Lissencephaly is a set of rare brain disorders and you will probably find that very few people have heard of it.  Lissencephaly is used as an 'umbrella' term to describe a range of disorders where the whole or parts of the surface of the brain appear smooth. 

The range of disorders include:

• Miller-Dieker Syndrome (MDS)
• Isolated Lissencephaly Sequence (ILS)
• Walker-Warburg Syndrome (WWS)
• Muscle-Eye-Brain disease (MEB)
• Subcortical Band Heterotopia (SBH)/Double Cortex
• Microlissencephaly (MLIS)
• Microcephaly with Simplified Gyral Patterns (MSG)
• X-linked Lissencephaly with Ambiguous Genitalia (XLAG)
• Baraitser-Winter syndrome (BWS)
• Micro Syndrome
• Lissencephaly with Cerebellar Hypoplasia (LCH)
• Lissencephaly with agenesis of the Corpus Callosum (LACC)
• Schizencephaly (SCH)*
• Polymicrogyria (PMG)*

You may have also been told that your child may be diagnosed with either agyria or pachygyria - these terms are generally used to describe the degree of brain smoothness and are often included in some of the diagnoses above.

The word lissencephaly is derived from the Greek "lissos" meaning smooth and "encephalos" meaning brain.  The human brain normally has a convoluted surface. In Lissencephaly these convolutions are completely or partially absent from the brain, or areas of it, have a smooth appearance. The convolutions are also called "gyri" and their absence is known as "agyria" (without gyri). In some cases convolutions are present, but thicker and reduced in number and you may hear the term "pachygyria" (broad gyri) being used. The diagnosis is usually made with the help of a CT Scan or MRI Scan of the brain.

* neither SCH or PMG are strictly lissencephaly, but are often included because of the similarity in brain scan appearance.  For more information on Polymicrogyria click here.

How is it caused?

We know that in Lissencephaly the brain develops normally in early pregnancy but then fails to progress normally after the third to fourth month. There are several causes and these can be identified in many children.

The different types of Lissencephaly generally have different causes.  These fall into four main categories:

1. An inherited genetic condition that may come from either one or both parents;
2. A new genetic mutation (i.e not inherited) that occurs in a gene that is critical for the correct development of the brain;
3. An infection from a virus during pregnancy;
4. An interruption of the blood supply to the foetus during pregnancy.

There have been a lot of advances recently in testing for some specific genetic problems, known to be the cause of some types of Lissencephaly, so these tests may he recommended in your family. Your paediatrician will be happy to discuss this with you and if necessary refer you to a Neurologist or Geneticist for further advice.  For some background on genetics and Lissencephaly, click here.

Obtaining an accurate diagnosis

Getting an accurate diagnosis can be important for a number of reasons.  Firstly, if the condition is genetic and has been inherited, it will allow you to understand the risk for future pregnancies and also whether other children you may have are also 'carriers' for the faulty gene.  Secondly, it is useful to meet other parents and children with the same condition so you may learn from each others experience.

You may never have been given a diagnosis other than Lissencephaly or pachygyria.  These are not full diagnoses and so you cannot determine the cause without a more detailed view from a neurologist, paediatrician or geneticist.  One very important element in the diagnosis is the brain scan.  An MRI scan is almost always superior for detailing the brain malformation especially for conditions like polymicrogyria where CT scans do not provide the resolution required.  Similarly,  these conditions are so rare many neurologists may never have seen a scan like this before or may not have adjusted the MRI scanner correctly to detail some of the small malformations that occur. In these instances it is important to be referred to specialists where the expertise may exist.

Many of these conditions have only recently come to light and been given new names.  There is also a considerable amount of research presently underway to identify the underlying causes.  For this reason it may not be possible to get an accurate diagnosis.   However, you child may be able to help provide the data required for research to come up with answers for many questions you may have.

If you would like to obtain a more accurate diagnosis see our Research page. 

Definitive Lissencephaly Information

For a medical overview on Lissencephaly visit  GeneClinics.  To access this information you will need to register (this is free) and then click on GeneReviews and enter Lissencephaly as the search word.

For a single page overview of all the different conditions which are included in, or similar to, lissencephaly try here.

For a brief overview of some of the Lissencephaly syndromes, the US National Library of Medicine has the following information:

It is worth noting that Lissencephaly does not always form part of a syndrome (a syndrome is where a condition manifests itself in more than one way).  Isolated Lissencephaly Sequence (ILS) is not a syndrome as the smooth brain is an isolated condition (there are no other abnormalities apart from the smooth brain).

What problems may my child suffer from?

All children with Lissencephaly suffer from mental retardation, the degree of which can vary considerably and is very dependant on the type of lissencephaly, the degree of malformation (i.e. whether the whole brain is affected or just a part of it) and also whether the child suffers from seizures.

Seizures or fits occur in a large percentage of children.   These may often be controlled by the use of anticonvulsant drugs or in some cases by a special diet, the 'Ketogenic diet'.

Feeding can be a problem.  Many children may have to use a Gastronomy (or G-tube) to feed if they are unable to swallow correctly.  Related to feeding problems is aspiration (the swallowing of food or other matter into the lungs).   This can be the source of infection which can cause pneumonia or other chest problems which can be life threatening.  Reflux (stomach contents coming back up through into the throat) can also be the cause of great discomfort.  Reflux can be treated with drugs or with surgery - the Nissen fundoplication.

Source : http://www.lissencephaly.org.uk/aboutliss/index.htm