Lissencephaly is a rare brain malformation where the brain’s surface lacks the typical folds (gyri) and grooves (sulci). The term translates to “smooth brain,” which describes the cerebral cortex in affected individuals. This lack of folding results from a disruption in fetal development and has significant consequences for neurological function.
Causes and Development
Lissencephaly stems from a disruption in neuronal migration during the 12th to 24th week of gestation. Normally, new nerve cells travel from deep within the fetal brain to the surface to form the cerebral cortex. When the genetic signals guiding this process are faulty, the migration is impaired, and the brain’s surface remains smooth.
Genetic mutations are the primary cause. Specific genes, such as LIS1 and DCX, provide instructions for creating proteins that are directly involved in the movement and placement of neurons. A mutation in the LIS1 gene is a common cause of classic lissencephaly (Type 1), resulting in a very smooth brain surface.
Cobblestone lissencephaly is another classification associated with different genetic mutations. In this form, migrating neurons overshoot their destination, creating clumps that give the brain’s surface a bumpy appearance. Non-genetic factors, such as first-trimester viral infections or insufficient oxygen to the fetal brain, may also contribute.
Signs and Symptoms
The signs of lissencephaly are apparent in infancy and vary in severity based on the brain malformation. A common physical indicator is microcephaly, where an infant’s head is small or fails to grow normally. Children may also have distinct facial features, like a small jaw or a high forehead.
Neurological and developmental issues are prominent. Seizures are a frequent symptom, affecting a majority of children and often beginning within the first year of life. These can manifest as infantile spasms, a serious seizure type that can impact development. Muscle-related problems are also common, ranging from spasticity (tight muscles) to hypotonia (weak muscle tone).
Feeding and swallowing difficulties (dysphagia) are another challenge, caused by uncoordinated or weak muscles. These issues can lead to poor nutrition and respiratory problems. The combination of these symptoms results in developmental delays, with many children struggling to reach milestones like sitting up, walking, or talking.
The Diagnostic Process
Diagnosis can begin before birth. A routine prenatal ultrasound may reveal abnormalities in the fetal brain’s structure, prompting a fetal magnetic resonance imaging (MRI) scan. This provides a more detailed view of the developing brain and can show the lack of folding.
After birth, diagnosis relies on brain imaging. An MRI or computed tomography (CT) scan can confirm a thickened cerebral cortex and assess the malformation’s severity. This assessment helps in understanding the potential challenges the child may face.
Genetic testing is recommended to determine the underlying cause. Analyzing a blood sample can identify mutations in genes known to cause the disorder. Pinpointing the genetic cause helps provide a more precise prognosis and allows for family genetic counseling.
Management and Prognosis
There is no cure for lissencephaly, so treatment focuses on managing symptoms and providing supportive care to improve quality of life. This care often involves a multidisciplinary team of healthcare professionals. A primary focus of medical management is controlling seizures with antiepileptic medications.
Nutritional support is another aspect of management. Due to feeding and swallowing difficulties, some children require a feeding tube for adequate nutrition and to reduce the risk of aspiration. Physical, occupational, and speech therapies are also used to manage complications and support development.
The long-term outlook is highly variable and depends on the severity of the brain malformation and related health complications. Life expectancy can be shortened, with respiratory disease being a common cause of death. While many children have developmental challenges, those with milder forms may experience only mild learning differences.