What to know about lissencephaly (smooth brain)

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Lissencephaly is a rare brain abnormality that occurs with certain neurological conditions. The word lissencephaly means “smooth brain.”

Lissencephaly causes a person’s brain to have fewer folds, also called convolutions. This causes it to appear smoother.

Conditions that cause lissencephaly may also cause a person’s head to be abnormally small. The medical term for this is microcephaly.

Children who have lissencephaly may also have an abnormal facial appearance and intellectual disabilities.

Symptoms of lissencephaly can vary from person to person.

A common symptom of the disorder is slow cognitive development and intellectual disability.

Lissencephaly can also cause a person to experience infantile spasms, a serious type of seizure.

Between 35–85% of children with lissencephaly experience infantile spasms. A child’s cognitive development will often slow with the onset of seizures.

A person with the disorder may have several physical signs. These include:

• an unusual facial appearance
• abnormally developed hands, fingers, and toes

Learn more about seizures in babies.

There are multiple types of lissencephaly. Most of them fall under two main categories. They are:

• Classic lissencephaly (Type 1). This type tends to cause the brain’s outer layer to have four layers instead of the normal six layers.
• Cobblestone lissencephaly (Type 2). This type causes the brain’s outer layer to appear pebbled or nodular. People with type 2 lissencephaly also often have abnormalities in the muscles and eyes.

These categories come from different genetic mutations but may present similarly.

Lissencephaly may occur in association with other syndromes and congenital abnormalities.

Conditions associated with lissencephaly include:

• Miller-Dieker syndrome. This is a condition caused by a genetic abnormality. It involves lissencephaly, distinctive facial features, and severe neurologic abnormalities, including intellectual disability and seizures.
• Walker-Warburg syndrome. This is a severe form of congenital muscular dystrophy that often affects the brain and eyes. Symptoms typically present at birth and include decreased muscle tone and weakness, developmental delay, intellectual disability, and seizures. Lissencephaly often occurs alongside Walker-Warburg syndrome.

A parent or carer for a child with these conditions should consult with a pediatrician. This can help them receive a correct diagnosis and possible molecular testing.

During the gestation period, while a fetus is in the womb, a process called neuronal migration occurs. In this process, nerve cells develop to form the brain structures and begin to function.

A defect in neuronal migration during the development of an embryo is what causes lissencephaly. This defect usually occurs between 12–24 weeks of gestation.

This defect results in the absence of normal development of two brain characteristics. These are:

• Gyri. The gyri are the bumps and ridges on the brain’s outer layer.
• Sulci. The sulci are the grooves that appear between the gyri on the brain’s outer layer.

Genetic causes

There are some genetic causes of lissencephaly. These are associated with mutations or deletions of specific genes.

Below are some known genetic causes of lissencephaly:

• LIS1. This gene is on chromosome 17p13.3. The mutation or deletion of the LIS1 gene can cause lissencephaly and Miller-Dieker syndrome.
• DCX. This gene is on the X chromosome. It plays a role in assisting neuronal migration. Mutations to the DCX gene can cause reduced folding in the cerebral cortex, causing a person to develop lissencephaly.
• ARX. This gene helps produce a protein that plays an important role in the brain. If the ARX gene has a mutation, a person can develop lissencephaly. Other symptoms of this mutation include the absence of certain parts of the brain, abnormal genitalia, and severe epilepsy.
• RELN. This gene helps produce certain proteins. If this gene has a mutation, a person can develop lissencephaly. They may also develop abnormalities in other parts of the brain, such as the hippocampus.

Nongenetic causes

Lissencephaly can be a rare complication of maternal viral infections.

If a pregnant person gets a viral infection, this can cause a defect in the fetus’s neuronal migration. This can cause it to develop lissencephaly.

Viruses such as cytomegalovirus (CMV) can also cause the developing fetus to have an insufficient supply of oxygenated blood to the brain. This can also cause lissencephaly.

A viral infection most commonly causes lissencephaly during the first trimester of the pregnancy.

However, as lissencephaly is rare, most pregnant people who get a viral infection during their first trimester will not have a baby with lissencephaly.

A lissencephaly diagnosis may involve a clinical evaluation and brain imaging tests.

These imaging tests may include CT scans and MRI scans. The results of these tests may allow a doctor to diagnose lissencephaly.

A medical professional may also confirm the diagnosis during pregnancy using testing such as:

• Cell-free fetal DNA. A medical professional takes a blood sample from the pregnant person. They then extract DNA from the pregnant person and fetus. A scientist then screens this sample for chromosomes that might increase the chance of lissencephaly.
• Amniocentesis. A medical professional extracts a sample of amniotic fluid, which is the fluid that surrounds the fetus in the womb. They then remove and test a small sample of cells from this sample. This test can check if the fetus has a genetic or chromosomal condition that could cause lissencephaly.
• Chorionic villus sampling (CVS). A medical professional takes a small sample of cells from the placenta. They then test these cells to see if the fetus has a genetic or chromosomal condition that could cause lissencephaly.

An electroencephalogram (EEG) is another test that a medical professional may use to check if a child has signs consistent with lissencephaly. During an EEG, a medical professional will record the brain’s electrical impulses.

An abnormal brain pattern may indicate that a person has changes in their brain function that could be related to lissencephaly. This may prompt further testing to help diagnose the condition.

A person may also undergo DNA analysis to help detect specific gene deletions and mutations. This can help a medical professional see if there are mutations or deletions in the genes linked to lissencephaly.

Some people with lissencephaly may suffer from aspiration of food or fluids.

This is when a person accidentally inhales food or liquids through their vocal cords. The food or liquid then moves into the airway, which can be dangerous.

Other possible complications include:

• respiratory diseases
• difficulty breathing
• difficulty feeding
• problems swallowing
• severe seizures

There is no cure for lissencephaly. Treatments for the condition aim to support children and manage their symptoms.

Treatment may aim to help the child improve the intake of nutrients. This is particularly important if the child experiences difficulty feeding.

A child may also receive anticonvulsant drugs. These aim to help prevent or control seizures.

A child’s outlook depends on the degree of their brain abnormalities.

Many children remain at an early developmental stage. Life expectancy may also be short — in many cases, the condition can be fatal before the age of 10.

Some may survive but show no significant development. Others may have near-normal development and may reach adulthood.

The most common causes of death are:

• aspiration of food or fluids
• respiratory disease
• severe seizures

Living with lissencephaly

There is no cure for lissencephaly, but some people’s development may improve over time.

A person may experience an improved quality of life if they are offered access to:

• physical therapy
• occupational therapy
• speech therapy

A feeding tube may also help to provide nutrition if a person has difficulties with eating.

Taking care of a child with lissencephaly

A parent or carer for a child with lissencephaly may need to offer comfort, feeding, and nursing support.

A parent or carer should consult a doctor or healthcare professional to further understand their child’s needs. The amount and type of treatments a child will need depends on the severity of the symptoms and associated conditions.

Some children may need extra equipment such as walking aids, communication tools, and feeding tubes. A parent or carer may also need to administer medications to help control seizures.

Lissencephaly is a rare genetic brain condition. It causes the brain’s outer layer to appear smooth.

Other symptoms include slow cognitive development, intellectual disability, an abnormally small head, muscle spasms, seizures, and deformed hands, fingers, and toes. A person with lissencephaly may also experience difficulty eating.

The condition affects people differently, but many children with lissencephaly do not live beyond 10 years of age. However, some people may live longer.

The most common causes of death for people with lissencephaly are the aspiration of food, respiratory disease, and severe seizures.

There is no cure for the condition. Treatment involves offering support, reducing symptoms, and improving quality of life.

A person with lissencephaly may receive support to help improve the intake of nutrients. They may also receive anticonvulsant drugs to help prevent or control seizures.

A person may also receive speech therapy, physical therapy, and occupational therapy to improve their quality of life.