lissencephaly 8

Lissencephaly: A Rare Brain Developmental Disorder

Lissencephaly, also known as "smooth brain," is a rare and severe brain developmental disorder that affects the normal formation of the cerebral cortex. This condition is characterized by the absence or abnormal development of the normal convolutions (folds) in the brain's surface.

Causes and Symptoms

Lissencephaly is caused by defective neuronal migration during embryogenesis, resulting in a lack of development of brain folds and grooves. The symptoms of lissencephaly can vary depending on the severity and type of the condition. Some common symptoms include:

• Cognitive and intellectual disabilities: Children with lissencephaly may experience significant delays in cognitive and intellectual development.
• Seizures: Seizures are a common symptom of lissencephaly, and can range from mild to severe.
• Physical disabilities: Lissencephaly can also cause physical disabilities, such as difficulty swallowing or feeding.
• Microcephaly: Some individuals with lissencephaly may have an abnormally small head (microcephaly).

Types of Lissencephaly

There are several types of lissencephaly, including:

• Isolated lissencephaly sequence (ILS): This is the most common type of lissencephaly, and is characterized by a smooth brain with absent or abnormally wide gyri.
• Subcortical band heterotopia (SBH): This type of lissencephaly is characterized by the presence of abnormal bands of neurons beneath the cortex.

Prognosis and Treatment

Unfortunately, there is no cure for lissencephaly. However, with proper medical care and support, individuals with this condition can lead fulfilling lives. The prognosis for lissencephaly varies depending on the severity and type of the condition, but most children with lissencephaly will require lifelong care and support.

References:

• [8] Isolated lissencephaly sequence (ILS) is a condition that affects brain development before birth.
• [5] Lissencephaly (/ ˌ l ɪ s ə n s ɛ f əl i /) literally means "smooth brain," and is a rare, gene-linked brain malformation characterized by the absence of normal convolutions (folds) in the cerebral cortex.
• [15] Clinical Description. Together, isolated lissencephaly sequence (ILS) and subcortical band heterotopia (SBH) comprise the "agyria-pachygyria-band" spectrum of cortical malformations that are caused by deficient neuronal migration during embryogenesis.

Common Signs and Symptoms of Lissencephaly

Lissencephaly, a rare congenital condition, can cause a wide range of symptoms in affected individuals. According to various sources [4][5][6][7][8], some common signs and symptoms of lissencephaly include:

• Unusual facial appearance: People with lissencephaly may have distinctive facial features that are different from the general population.
• Difficulty swallowing: Some individuals with lissencephaly may experience difficulty swallowing, which can lead to feeding problems and failure to thrive.
• Failure to thrive: Lissencephaly can cause a range of developmental delays, including failure to gain weight or grow at a normal rate.
• Muscle spasms: Muscle spasms and seizures are common symptoms of lissencephaly, which can be severe and difficult to control.
• Seizures: Seizures are a hallmark symptom of lissencephaly, and can range from mild to severe in intensity.
• Severe psychomotor development delay: Lissencephaly often results in significant delays in motor skills development, such as sitting, standing, or walking.
• Mental retardation: In some cases, individuals with lissencephaly may experience intellectual disability or mental retardation.

These symptoms can vary in severity and presentation from person to person, and may be detected via ultrasound during fetal development or confirmed through prenatal MRI [3][7].

Diagnostic Tests for Lissencephaly

Lissencephaly, a rare birth defect involving an abnormally smooth brain, can be diagnosed using various tests. Here are some of the diagnostic tests used to diagnose lissencephaly:

• Fetal Magnetic Resonance Imaging (MRI) or Ultrasound: Prenatal diagnosis is usually possible after 27 weeks of gestation with fetal MRI or ultrasound.
• Head Ultrasound: Once your baby is born, providers use head ultrasound to help diagnose lissencephaly. This noninvasive diagnostic imaging test uses high-frequency sound waves to create real-time pictures or videos of internal organs or other tissues.
• Fetal Brain MRI at ≥32 weeks' gestation: Fetal brain MRI at 32 weeks' gestation or later can also aid in the diagnosis of lissencephaly.
• Detailed Ultrasound Examination, including Neurosonography: A detailed ultrasound examination, including neurosonography, may be conducted to help diagnose lissencephaly.

Genetic Testing

In addition to imaging tests, genetic testing is also used to diagnose lissencephaly. Genetic studies of 17 genes associated with lissencephaly revealed that:

• LIS1 mutation or deletion accounts for 40% of the patients: LIS1 mutation or deletion was found in 40% of the patients.
• DCX mutation, followed by TUBA1A and DYNC1H1: DCX mutation was associated with 23% of the patients, followed by TUBA1A (5%), and DYNC1H1 (3%).

These diagnostic tests can help identify lissencephaly and provide a more accurate diagnosis. However, it's essential to note that establishing care with an engaged and dedicated primary care provider may improve care and shorten the time it takes to reach an accurate diagnosis.

References

• [8] Internal proficiency testing is conducted biannually in compliance with all CAP regulations.
• [9] Providers use the following imaging tests to help diagnose lissencephaly once your baby is born: Head ultrasound, Fetal brain MRI at ≥32 weeks' gestation, and Detailed ultrasound examination, including neurosonography.
• [14] The diagnosis and the prevalence of lissencephaly will increase with improving imaging technology. Genetic studies of 17 genes associated with lissencephaly revealed that LIS1 mutation or deletion accounts for 40% of the patients, and DCX mutation was associated with 23% of the patients.

Treatment Options for Lissencephaly

While there is no cure for lissencephaly, supportive care can help alleviate symptoms and improve quality of life. In terms of drug treatment, the focus is on managing specific symptoms rather than directly addressing the underlying condition.

• Calpain inhibitors: Research suggests that calpain inhibitors may hold promise in treating neuromuscular and neurodegenerative diseases, including lissencephaly [7].
• Gastrostomy tube placement: Children who experience difficulty feeding and swallowing may require a gastrostomy tube to ensure adequate nutrition [8].
• Medications for seizures: Seizures are a common symptom of lissencephaly. Medications such as anticonvulsants can help manage seizure activity.
• Pain management: Supportive care may also involve pain management strategies to improve comfort and reduce discomfort.

It's essential to note that treatment plans are tailored to the individual child's needs, and a multidisciplinary team of healthcare professionals works together to develop a comprehensive plan [1].

Differential Diagnosis for Lissencephaly

Lissencephaly, a rare congenital condition, can be challenging to diagnose due to its similarities with other brain malformations. The differential diagnosis for lissencephaly involves considering various disorders that share similar clinical presentations and genetic mutations.

Types of Lissencephaly

There are two main categories of lissencephaly:

• Classic Lissencephaly (Type 1): This type is characterized by a smooth brain appearance, with absent gyri and/or broad simple gyri. Classic lissencephaly can be distinguished from other disorders through its mode of inheritance, grade and gradient of lissencephaly or subcortical band heterotopia (SBH), presence of other congenital anomalies, clinical features, and results of molecular genetic testing.
• Cobblestone Lissencephaly (Type 2): This type is also known as thin lissencephaly. It is morphologically and etiologically distinct from classic lissencephaly.

Differential Diagnoses

Some disorders that should be considered in the differential diagnosis for lissencephaly include:

• Miller-Dieker syndrome: A rare genetic disorder characterized by a deletion of part of chromosome 17, leading to severe intellectual disability and physical abnormalities.
• Norman-Roberts syndrome: A condition similar to type I lissencephaly but without the deletion of the DCX gene.
• Subcortical band heterotopia (SBH): A disorder characterized by abnormal brain development, where bands of neurons are located beneath the cortex.

Imaging and Molecular Genetic Testing

Imaging studies, such as MRI, can help in diagnosing lissencephaly. Thin slice volumetric T1-weighted images, axial and coronal T2-weighted images, and other imaging modalities should be used to assess the detail and associated structural abnormalities. Molecular genetic testing can also aid in identifying the underlying genetic mutations responsible for lissencephaly.

References

• [3] Lissencephaly is a rare congenital condition that causes a developing brain to appear smooth instead of having normal bumps and folds.
• [10] Differential Diagnosis There are more than 20 types of lissencephaly, most of them are listed under 2 main categories: Classic lissencephaly (Type 1) and Cobblestone lissencephaly (Type 2).
• [11] Classic Lissencephaly. The differential diagnosis of classic lissencephaly is summarized in Table 3.
• [13] Differential diagnoses; OVERVIEW. Lissencephaly is a malformation of cortical development, where there is deficient gyration (folding) in the cerebral cortex, resulting in absent gyri (agyria) and/or broad simple gyri (pachygyria).
• [15] Classic lissencephaly is morphologically and etiologically distinct from lissencephaly type 2, which is also called cobblestone lissencephaly, and from thin lissencephaly.