Lissencephaly - A Rare Congenital Anomaly

What Is Lissencephaly?

Lissencephaly is a rare birth defect that is also known as a ‘smooth brain’ due to the absence of folds in the parts of the brain. This condition usually develops during pregnancy when the fetus’s brain is developed in the wrong manner. Normally, the human brain has folds or bumps (gyri) and grooves or indentations (sulci), which are essential as they separate regions of the brain and increase its surface area and cognitive (mental) ability.

Lissencephaly is characterized by an extremely small head and the absence of convolutions (folds) in the cerebral cortex (part of the brain). Due to the lack of normal development of the brain and the absence of gyri and sulci, the brain appears smooth, hence the name ‘smooth brain.’ Since it is a rare condition, it is estimated to affect one in every hundred thousand newborn babies. It is generally caused by genetic factors, and sometimes the cause can be non-genetic factors. It affects the growth and development of the brain, and the size of the head is usually smaller than normal with characteristic facial abnormalities.

Lissencephaly is often associated with other disorders, and it can be difficult to distinguish between these conditions clinically. Some of these conditions include:

1. Walker-Warburg Syndrome - This syndrome causes severe muscle wasting and weakness.

2. Miller-Dieker Syndrome - Children with this syndrome have large foreheads, small jaws, and other facial problems and breathing problems, and they grow more slowly.

3. Norman-Roberts Syndrome - This syndrome causes seizures, wide-set eyes, and reduced mental abilities.

What Are the Symptoms of Lissencephaly?

Symptoms of lissencephaly depend on how severe the condition is and if it is part of a syndrome. Some children do not show evident symptoms and have normal growth, while others experience serious symptoms.

Symptoms of lissencephaly are:

• Convulsions or seizures.

• Developmental delays like delay in speech, language, and social skills.

• Difficulty swallowing (dysphagia).

• Learning difficulties and mental disability.

• Muscle spasms.

• Facial abnormalities such as prominent upper lip and abnormal positioning of jaws.

• Failure to thrive (weight faltering).

• Microcephaly (smaller-than-normal size of the head).

• Psychomotor function problems like movement, dexterity, and hand-eye coordination.

• Congenital limb differences involving their fingers, toes, and hands.

What Are the Causes of Lissencephaly?

The causes of lissencephaly can be genetic or non-genetic factors. These factors cause a defective neuronal migration during fetal development, the process that is responsible for the movement of nerve cells from their place of origin to a permanent location within the cerebral cortex.

• Genetic Causes - Genetic mutations or changes in the sequence of DNA (deoxyribonucleic acid) cause lissencephaly. A child can acquire a genetic mutation from either or both parents. However, some children may have mutations without any family history of genetic mutations. Many genetic changes have been discovered that cause lissencephaly. Some of these affected genes include DCX (doublecortin), LIS1 (PAFAH1B1), ARX (aristaless related homeobox), and RELN (reelin).

• Non-genetic Causes - Apart from genetic causes, lissencephaly can also be caused due to non-genetic problems. They include viral infection of the pregnant woman or fetus during the first three months of the pregnancy and a lack of blood supply to the developing brain of the fetus.

How to Diagnose Lissencephaly?

Lissencephaly can be diagnosed at birth or after birth. Sometimes, lissencephaly is diagnosed during pregnancy if it is suspected because of a family history or a prenatal ultrasound. It can also be diagnosed at birth through physical examination and head imaging tests.

Tests Done Before the Birth

• Amniocentesis - It is a test done to check if the fetus has any genetic disorder. It involves collecting a sample of amniotic fluid (a slightly yellowish fluid that surrounds the baby in the womb during pregnancy) and testing in the laboratory.

• Cell-free Fetal DNA Test - This test involves testing blood samples of the pregnant mother and baby to check for the presence of any genetic or chromosomal conditions.

• Chorionic Villus Sampling (CVS) - It is a test done to check for chromosomal abnormalities by testing a sample of the placenta (an organ that develops during pregnancy and connects the mother’s uterus to the fetus).

Tests Done After the Birth

• Computed Tomography (CT) Scan of the Head - This imaging test uses X-ray and computer technology to create images of the inside of the head. This allows the healthcare provider to check for the presence or absence of the folds of the brain.

• Ultrasound of the Head - This imaging test creates images of the structures inside the head using sound waves. This test also helps to check for folds in the brain.

• Magnetic Resonance Imaging (MRI) Scan of the Brain - This test creates detailed images of the brain using radio waves and magnets.

• Electroencephalogram (EEG) - Using this test, the electrical activity of the brain can be tested. It helps find potential areas of seizure activity in the brain.

To confirm the diagnosis, healthcare providers can use DNA studies such as specific gene mutational analysis and chromosomal analysis to check for mutations causing lissencephaly.

What Are the Treatment Options for Lissencephaly?

There is no cure for lissencephaly as of now, but some people improve over time. The treatment plan focuses on controlling and addressing the symptoms of the affected child. To provide effective treatment, a team of doctors involving pediatricians, neurologists, gastroenterologists, nutritionists, respiratory therapists, and physical and occupational therapists may be required. The treatment options include:

• Anti-seizure medications are given to help prevent or control seizures.

• Measures are taken to improve the intake of nutrients of an affected child with feeding difficulties, such as G-tube (gastrostomy tube) or swallowing and speech therapy.

• To treat hydrocephalus (fluid buildup in the brain) can be treated with a ventriculoperitoneal (VP) shunt.

• Physical and occupational therapy to help with muscle stiffness and motor development.

Conclusion:

Lissencephaly is a rare birth anomaly that can not be cured, but the symptoms can be managed through various treatment options. Also, cases of lissencephaly can not be prevented, unfortunately, and many affected children generally have a short life span of approximately ten years. The prognosis for this condition varies depending on the severity. However, early and consistent therapy can be helpful for some children.