Lissencephaly

What is Lissencephaly?

Lissencephaly is a very rare neurological disorder that occurs when the folds of the brain do not develop normally. If you looked at images of a healthy brain, you would see a series of folds, wrinkles and indentations and this enables a large amount of tissue access into a relatively small space. In the case of lissencephaly, the folding process does not occur properly and the brain appears smooth.

It is estimated that lissencephaly affects around 11 in every million live births. Other names for lissencephaly include agyria and lissencephaly type I.

Lissencephaly is closely related to Walker-Warburg syndrome and Miller-Dieker syndrome.

What causes lissencephaly?

Experts believe that the majority of cases of lissencephaly are genetic and research has identified defects on five specific genes related to this condition, including LIS1, ARX, RELN, DCX and 14-3-3ε. In most cases, signs of lissencephaly develop in pregnancy between 12 and 14 weeks. At this time, the nerve cells in the brain would usually relocate to different parts of the brain but in cases of lissencephaly, the nerve cells do not move and this has an impact on development.

Symptoms of lissencephaly

Babies born with lissencephaly may develop the following symptoms:

• a smaller than average head (also known as microlissencephaly)
• failure to thrive (failing to gain weight, grow and develop as expected)
• dysphagia (difficulty swallowing)
• feeding problems
• seizures
• muscle spasms
• impaired cognition
• lack of motor skills
• hypotonia (lack of muscle tone)

There is also a risk of complications, which may be fatal.

Diagnosing lissencephaly

If there is an increased risk of lissencephaly (for example, there is family history on one or both sides), early and frequent antenatal scanning may be recommended. The folds usually start to become visible between weeks 25 and 30, but an early scan can be done at around 20 weeks.

After birth, a number of tests can be ordered if a doctor suspects that a baby may have lissencephaly, including imaging scans (ultrasound, CT and MRI scans). If a diagnosis of lissencephaly is suspected, the results of tests will be used to grade the severity. Grade 1 is the most serious form and relates to generalised smoothness (also known as agyria). It is very rare and grade 3 is the most common form. Grade 3 lissencephaly is characterised by thickening (also known as pachgyria) at the front and sides and a degree of agyria around the brain.

Treatment for lissencephaly

It is not possible to correct or cure lissencephaly and treatment is designed to support children and help to alleviate symptoms when possible. Children may need help with feeding, therapy to improve movement and medication to control seizures. In cases where excess fluid collects on the brain, surgery may be recommended.

What is the outlook?

The outlook depends heavily on the severity of lissencephaly. In the most severe cases, children experience significant mental retardation and delayed development and life expectancy is around 10 years and death is usually caused by complications, such as aspiration, seizures and susceptibility to infections. In milder cases, life expectancy may not be affected.