Lissencephaly

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at September 23, 2016
StartDiseasesLissencephaly

Lissencephaly is a rare brain malformation that occurs during fetal development. The condition is characterized by an absence of the wrinkles, grooves, and folds that are normally present in the brain’s cerebral cortex. Children born with this congenital disorder often have severely impaired neural function and a shortened lifespan. 

Contents

Definition & Facts

The term lissencephaly is derived from the Greek words for “smooth brain.” It is estimated that there are 11.7 cases of lissencephaly per every one million births in the United States. Recognition of the condition is on the rise due to the increased availability of advanced medical imaging techniques for use during neurological evaluations.

Lissencephaly typically develops between the 12th and 14th weeks of pregnancy. During this point in fetal development, nerve cells start to migrate to other areas of the brain. If this does not occur, the baby can develop lissencephaly.

The condition can occur on its own or in conjunction with other genetic conditions, including Miller-Dieker syndrome and Walker-Warburg syndrome, that are characterized by distinctive facial features and brain and eye abnormalities

Symptoms & Complaints

Infants born with lissencephaly often have an abnormally small head (microcephaly), which is known more specifically as microlissencephaly. Other physical manifestations may include subtle facial changes, including the following:

The condition is typically associated with severe to profound intellectual disability, decreased motor abilities and muscle spasms, failure to thrive, and growth retardation, and poor feeding and difficulty swallowing (dysphagia).

Babies with the condition may experience frequent seizures as the result of uncontrolled electrical activity in the brain. Other physical abnormalities, such as heart disease and kidney disease can also occur if lissencephaly presents along with other syndromes. It is possible for infants with lissencephaly to appear perfectly normal at birth and for the symptoms to become noticeable around two to six months of age.

Causes

There is some belief that lissencephaly may be caused by several different factors. Recent research indicates that the condition is primarily a genetic disorder in nature. Specific malformations or mutations in various genes have been linked to lissencephaly. The mutations believed to contribute to the condition occur in genes located on chromosome 17 and the X chromosome.

Although more research is needed, some of the genes believed to be linked to lissencephaly include L1S1, ARX, RELN, DCX, and 14-3-3ɛ. Some researchers suggest that fetal injury, such as a disruption in blood flow or a viral infection, may also contribute to the development of lissencephaly. It is not clear whether or not the condition can be inherited. 

Diagnosis & Tests

In some instances, lissencephaly may be diagnosed before birth through the use of specialized testing, including amniocentesis or chorionic villus sampling, also known as CVS. An amniocentesis involves obtaining a small sample of amniotic fluid surrounding the fetus. Chorionic villus sampling is a procedure in which a small sample of tissue is removed from the placenta. Upon closer examination, these fluid and tissue samples may indicate an chromosome abnormality in chromosome 17.

Even if the effects of lissencephaly are not apparent at birth, they will usually develop within a few months when the child stops progressing developmentally and begins to have seizures. These abnormal electrical impulses in the brain may be identified by using electroencephalography, commonly referred to as an EEG.

If a baby shows any indication of a brain development issue, the doctor will typically order one or more imaging scans. These may include an ultrasound, magnetic resonance imaging (MRI), or computed tomography (CT) scan. The scans will reveal signs of smoothness known as agyria and thickening called pachygyria.

If a diagnosis of lissencephaly is confirmed, the doctor will determine the grade or degree to which the brain is affected. Grade 1 lissencephaly is characterized by generalized agyria and typically has the most severe symptoms. The most common form of lissencephaly is grade 3 in which there is some agyria present throughout the brain and noticeable thickening at the sides and front of the brain. Although limited to specialized research laboratories, there are DNA tests available to identify the specific genetic mutations responsible for causing lissencephaly.

Treatment & Therapy

There is currently no cure or treatment to reverse the effects of lissencephaly. Treatment measures are aimed at supporting and comforting the patient and the family. Specific medical interventions may be used to deal with certain symptoms and complications of the condition. For example, occupational therapy and physical therapy may be beneficial in preventing loss of muscle tone and contracture.

If the child has difficulty eating and swallowing, a surgical procedure to insert a gastrostomy tube into the abdomen can reduce the risk of aspiration. Anticonvulsant medications may be used to treat seizures in some children; however, these seizures are often very difficult to control. In a small number of lissencephaly cases, the child may develop hydrocephalus in which an excessive amount of cerebrospinal fluid accumulates around the brain. In this situation, a surgical procedure may be necessary to implant a cerebral shunt to allow the fluid to drain away from the brain.

The outlook for an infant born with the condition can vary significantly. A child with a mild form of the condition may experience near-normal brain function and development. Unfortunately, many children with severe lissencephaly die before they reach the age of 10. These children typically stop developing mentally at the level of a 3 to 5-month-old. According to the National Institute of Neurological Disorders, the most common causes of death include respiratory disease, seizures, and aspiration of fluids or food.

Prevention & Prophylaxis

There is no way to prevent lissencephaly, though a number of studies are underway to better understand the complex process of neural development and neuronal migration. It was one of these studies that led to the discovery of the genes responsible for lissencephaly.

The hope is that further research will lead to treatments and preventative measures for these kinds of disorders. Parents of children diagnosed with lissencephaly are encouraged to seek help from specialists in the condition and family support groups.