Lissencephaly Overview

Symptoms, Causes and Treatment of Lissencephaly in Children

Drawing of a brain
What is lissencephaly and what happens when a child is diagnosed with this condition?. BSIP / Contributor / Getty Images

What is lissencephaly and what are the symptoms? How is the diagnosis made and what treatment options are available?

Overview

Lissencephaly is an uncommon neurological condition which often results in severe developmental delays and difficult to control seizures. It is a condition that results from the defective migration of nerve cells during fetal development.

The word lissencephaly comes from two Greek words: lissos, meaning "smooth," and enkaphalos, meaning "brain." If you look at a normal brain, the gray matter (cerebrum) has ridges and valleys in its surface.

In lissencephaly, the brain surface is almost completely smooth. This abnormal development of the brain occurs during pregnancy, and can actually be seen on an intrauterine MRI by 20 to 24 weeks gestation.

Lissencephaly may occur alone or as part of conditions such as Miller-Dieker syndrome, Norman-Roberts syndrome, or Walker-Warburg syndrome. The condition is considered very uncommon but not rare, occurring in roughly one out of 100,000 babies. (A rare disease is defined as one occurring in fewer than one in 200,000 people).

Causes

There are several possible causes of lissencephaly. The most common cause is a genetic mutation in an X-chromosome linked gene known as DCX. This gene codes for a protein called doublecortin which is responsible for the movement (migration) of nerve cells (neurons) in the brain during fetal development. Two other genes have also been implicated in the causation.

Injury to the fetus due to a viral infection or insufficient blood flow to the brain are additional possible causes. The "damage" is thought to occur when a fetus is between 12 and 14 weeks gestation, either late in first trimester or early second trimester.

Symptoms

There are a wide range of symptoms that may occur in people diagnosed with lissencepahly.

Some children have few if any of these symptoms and other may have many. The severity of symptoms can also vary widely. Possible symptoms of lissencephaly include:

  • Failure to thrive: Failure to thrive is a condition often seen in newborns in which growth is not occurring as expected. It can have many causes.
  • Intellectual impairments: Intelligence can range from near normal to profound impairments.
  • A seizure disorder: A seizure disorder occurs in around 80 percent of children with the condition.
  • Difficulty swallowing and eating.
  • Difficulty controlling his/her muscles (ataxia).
  • Initial reduced muscle tone (hypotonia) followed by stiffness or spasticity of arms and legs.
  • Unusual facial appearance with a small jaw, high forehead, and indentation of the temples. Abnormalities of the ears and upturned nasal openings may also be noted.
  • Abnormalities of the fingers and toes, including extra digits (polydactyly).
  • Developmental delays that can range from mild to severe.
  • A smaller than normal head size (microcephaly).

Diagnosis

The diagnosis of lissencephaly is often not made until a child is a few months old, and many children with the condition appear healthy at the time of delivery. Parents usually note that their child isn't developing at a normal rate around the age of 2 to 6 months.

The first symptom may be the onset of seizures, including a severe type referred to as "infantile spasms." It can be difficult to get the seizures under control.

If lissencephaly is suspected based on the child's symptoms, ultrasound, magnetic resonance imaging (MRI), or computed tomography (CT scan) can be used to look at the brain and confirm the diagnosis.

Treatment

There is no way to directly reverse the effects of lissencephaly or cure the condition, but there is much that can be done to ensure the best quality of life for the child. The goal of treatment is to help every child with lissencephaly reach his or her potential level of development.

Treatment modalities which can be helpful include:

  • Physical therapy to improve range of motion and help with muscle contractures.
  • Occupational therapy.
  • Seizure control with anticonvulsants.
  • Preventive medical care, including careful respiratory care (as respiratory complications are a common cause of death).
  • Feeding assistance. Children who have difficulty with swallowing may need a feeding tube placed.
  • If a child develops hydrocephalus ("water on the brain"), a shunt may need to be placed,

Prognosis

The prognosis for children with lissencephaly depends on the degree of brain malformation. Some children may have near-normal development and intelligence, though this is usually the exception.

Sadly, the average life expectancy for children with severe lissencephaly is only around 10 years. The cause of death is usually aspiration (inhaling) of food or fluids, respiratory disease, or severe seizures (status epilepticus). Some children will survive but show no significant development, and children may remain at a level which is ordinary for a 3 to 5 month old.

Because of this range in outcomes, it is important to seek the opinion of specialists in lissencephaly and support from family groups with connection to these specialists.

Research

The National Institute of Neurological Disorders and Stroke conducts and supports a wide range of studies that explore the complex systems of normal brain development, including neuronal migration. Recent studies have identified genes that are responsible for lissencephaly. The knowledge gained from these studies provides the foundation for developing treatments and preventive measures for neuronal migration disorders.

A Word From Verywell

If your child has been diagnosed with lissencephaly, or if you child's physician is considering the diagnosis, you are probably terrified. What does this mean today? What will this mean a week from now? What does this mean 5 years or 25 years down the road?

Spending some time learning about your child's disorder (whether diagnosed or just being considered) may not alleviate all of your anxieties, but will put you in the driver's seat. With any form of medical condition in ourselves or our children, being an active participant in care is crucial.

Gathering your support system is also crucial. In addition, it's very helpful to connect with other parents who have children with lissencephaly. No matter how loving or helpful your friends and family, there is something special about talking to others who have faced similar challenges. Support networks for parents also provide an opportunity to learn what the latest research is saying.

As a parent, it's important to take care of yourself. Your emotions will probably be all over the board and that's to be expected. You may find yourself hurting when you see other parents with healthy children, and wonder why life can be so unfair. Reach out to those who can give you unconditional support and allow you to share what you are really feeling at this time.

Sources:

National Institute of Neurological Disorders and Stroke. Lissencephaly Information Page. https://www.ninds.nih.gov/Disorders/All-Disorders/Lissencephaly-Information-Page

Shahsavani, M., Pronk, R., Falk, R. et al. An In Vitro Model of Lissencephaly: Expanding the Role of DCX During Neurogenesis. Molecular Psychiatry. 2017 Sep 19. (Epub ahead of print).

Williams, F., and P. Griffiths. In Utero MR Imaging in Fetuses at High Risk of Lissencephaly. British Journal of Radiology. 2017. 90(1072):20160902.

Continue Reading