Lissencephaly

What is Lissencephaly?

Lissencephaly, literally meaning “smooth brain”, can be defined as a rare type of brain formation disorder that is caused by improper neuronal migration during the 12th-24th weeks of gestation. This results in a deficiency in the formation of the gyri or brain folds and the grooves (sulci).

This is actually a type of cephalic disorder that often leads to microcephaly (abnormally small head). A genetic factor is believed to be responsible for the development of this disorder.

Lissencephaly Types

Modern diagnostic procedures such as neuroimaging techniques and genetic testing have paved the way for physicians to obtain more insights into various migration disorders which have broadened the overall spectrum of lissencephaly. There are nearly 20 varied types of this condition that make up the total spectrum. There are likely to be more causes which have not been identified yet.

There are various systems for classifying the condition of lissencephaly. A major distinction is the classic or Type I versus the cobblestone or Type II. However, there are also some other systems adding additional forms which confirm into neither of these above mentioned categories. Some of the major types of this disorder are mentioned below:

Classic or Type I Lissencephaly

It includes:

LIS1

This type of the disease results from mutation in the PAFAH1B1 gene; it is subdivided into the following categories:

  • Miller–Dieker syndrome
  • Type I isolated Lissencephaly

LISX1

It arises as a result of doublecortin gene mutation.

Type I isolated lissencephaly

It originates without any other known genetic disorders.

Cobblestone or Type II Lissencephaly

  • Fukuyama Syndrome
  • Muscle-eye-brain disease
  • Walker–Warburg syndrome; it is also known as HARD (E) syndrome
  • LIS2: The Norman-Roberts syndrome (characterized by mutation of the reelin gene)
  • LIS3: TUBA1A
  • LISX2: ARX
  • Microlissencephaly (microcephaly and lissencephaly)

Other Types

  • LIS2: The Norman-Roberts syndrome (characterized by mutation of the reelin gene)
  • LIS3: TUBA1A
  • LISX2: ARX
  • Microlissencephaly (microcephaly and lissencephaly)

Lissencephaly Causes

This health condition can be caused by viral infections that affect the fetus or the uterus during the period of the first trimester. Insufficient supply of blood to fetal brain earlier during pregnancy can also lead to lissencephaly. A number of genetic attributes are also held responsible for this disease. These include mutation of reelin gene on the chromosome 7 and also mutations of other genes on chromosome 17 (LIS1) and the X chromosome (XLIS or Doublecortin).

A third gene, known as the TUBA1A gene, is also held responsible for this disorder.

Lissencephaly Symptoms

Children affected by this disorder may display various symptoms like:

  • Ataxia
  • Seizures
  • Microcephaly
  • Failure to thrive
  • Difficulty in swallowing
  • Unusual facial appearance
  • Hypotonia or muscle spasticity
  • Severe psychomotor retardation
  • Anomalies of the fingers, hands, or toes
  • Spasticity or stiffness of the arms and legs

Lissencephaly Diagnosis

The condition is normally diagnosed during birth or within the first few months of life with the help of imaging tests, such as:

  • Magnetic resonance imaging (MRI) scan
  • Computed tomography (CT) scan
  • Ultrasound scan

Prenatal diagnosis may include regular usage of complex ultrasounds which may indicate presence of any cerebral abnormality. However, this diagnostic method should also be complemented by the other procedures such as NMR and genetic studies.

Examinations for detecting cerebral anomalies using ultrasounds should not be carried out unless there is a strong indication for brain malformations suggested by the family’s medical history and/or other factors. The week 20 of pregnancy is the earliest point in time when signs of abnormal brain development can first be seen, although the general trend of ultrasounds revealing such symptoms is around week 25-30. Up until this time, the brain of the fetus generally has a rather smooth appearance. Chorionic villus sampling test can be conducted for some suspected cases of this disorder where a genetic mutation is held responsible.

Lissencephaly Differential Diagnosis

Diagnostic interpretation of this disorder should be handled with care and discernment as signs of this condition is often misinterpreted for another cerebral malformation disorder known as polymicrogyria.

Lissencephaly Treatment

The treatment of this condition is dependent on the intensity and location of the brain anomalies. Patients may require supportive nursing care. The seizures associated with the disease can be managed with anticonvulsant medications and the hydrocephalus may need shunting. A gastrostomy tube can be used if feeding poses a challenge. Physical as well as occupational therapy can help to alleviate the symptoms of pneumonia and muscle contractures.

Lissencephaly Prognosis

The outcome for this condition depends on the extent of brain malformation. Numerous patients show no major signs of development beyond 3 to 5-months after birth. Some individuals may display near-normal intelligence and development. Life expectancy for the patients of this condition can vary greatly. With proper medical treatment and care, many children can live up to their teen years. However, a lot of sufferers die before they reach 10 years of age. Respiratory diseases are the principal causes of death associated with lissencephaly. Other factors causing death include severe seizures or aspiration of foods or fluids.

Lissencephaly Pictures

The following pictures demonstrate the patterns of abnormal brain formation that are characteristic of this condition.

Picture of Lissencephaly

Picture 1 – Lissencephaly

Image of Lissencephaly

Picture 2 – Lissencephaly Image

Lissencephaly is a rare type of brain formation disorder which is characterized by abnormal development of the gyri and sulci. Children born with this disease generally suffer from severe neurological impairment. Although many patients die within a short time after birth, proper treatment may help in prolonging survival span for a number of years.

Leave a Reply