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Lissencephaly
Sunday, 31 August 2003
Monday, 12 January 2004

What

Lissencephaly is an abnormality of brain formation which causes the surface of the brain to be smooth rather than convoluted. Usually the surface is formed by a complex series of ridges (called gyri or convolutions) and valleys (sulci). Children with lissencephaly have absent or partially formed convolutions. During early pregnancy, the fetus’s nerve cells in the brain begin to divide in the center of the brain near a cavity called the central canal. These newly formed nerve cells depend on support cells to climb up a pathway to reach the outside surface, or cortex of the brain. Each new wave of nerve cells must climb above the preceding waves. The last-born cells are closest to the surface, resulting in an “inside-out” pattern. In lissencephaly, the nerve cells cannot migrate to the surface so they are stuck in an abnormal position. The cortex becomes thick with incorrect layering, so the cells cannot make their usual connections with other nerve cells.

Who

The frequency of Lissencephaly in girls and boys depends on the specific gene mutation involved. Lissencephaly type I is termed classical or isolated lissencephaly sequence (ILS) and primarily affects the outer region of the brain, or cortex. Children with type II may have additional defects of the brain or eyes and most develop hydrocephalus, where cerebral spinal fluid accumulates in the brain and builds up pressure. Lissencephaly can also be found is association with other syndromes such as Miller-Dieker, which causes facial abnormalities.

Signs and Symptoms

Children with classical type 1 or ILS appear as normal infants for the first few months. Parents are first likely to notice a lack of following with the eyes, fleeting smiles, and floppiness of the body. The following signs will be inactivity of the body, poor head control, poor feeding leading to slow weight gain or seizures. The seizures can be tonic (sudden stiffening of the body from moments to minutes), clonic (rhythmic jerking of the head, arms and legs) or absence (staring spells). After 2-6 months, infants may show signs of slow development, such as lack of rolling over, sitting up, reaching for objects, vocalizing and seeming interested in things. Although the infants do progress, they tend to fall further behind children their same age. Some may have very small head size and weak breathing leading to episodes of pneumonia. As the children get older, they develop spasticity of their muscles which causes tight rigid body postures leading to muscle and joint contractures, and more difficulty with eating and swallowing as seen in choking, gagging, and spitting out of food. Children can vary in the severity of Lissencephaly, but most will have severe mental dysfunction and poor control of their body movement.

Possible Causes

Genetic factors as well as some environmental factors seem to be responsible for the majority of Lisssencephaly cases. Genetically, a missing piece on chromosome 17 has been implicated in type 1 ILS which is also the site for Miller-Dieker syndrome. The genetic transmission is thought to be inherited from either an affected mother or father, or as spontaneous alteration of genetic material as the fetus grows. The environmental factors of exposure to the mother during the first trimester of pregnancy seem to include retinoic acid, methylmercury and radiation, and the role of viral infection is unclear at this time.

Diagnosis

The clinical diagnosis of Lissencephaly is suspected by the signs and symptoms described above, but these are quite general and non-specific. A more confirming diagnosis can be made initially by obtaining a CT (computed tomography) or MRI (magnetic resonance imaging) scan that shows a smooth brain with the absence of convolutions. Chromosomal analysis can be obtained as well and is especially useful when there is a history of other family members having lissencephaly.

Treatment

Current treatment addresses the symptoms. Therapy designed by physical and occupational therapists is focused to strengthening weak muscles, gaining better motor control, loosening tight rigid muscles and preventing contractures of the joints. Neurologists evaluate the seizure activity and prescribe anti-seizure medication to help control seizures, which can be quite difficult depending on the types and frequency of seizures that the child experiences. Discussion with gastroenterologist physicians and nutritionists is essential to determine the optimal nutritional feeding and strategies so that the child continues to gain weight and grow. Ophthalmologists (eye doctors) are needed to assess the child’s visual ability. Surgery is available to relieve the pressure of fluid accumulation (hydrocephalus) in the brain. Child development centers and special education programs in the schools are focused to optimizing the child’s best efforts to participate in the activities of daily living.

Prognosis

The prognosis of children with lissencephaly depends on the type, the severity, and the response to treatment. Your physicians (often a pediatrician, neurologist ophthalmologist and gastroenterologist) can discuss the prognosis of your individual child when the full assessment of the brain and any associated abnormalities is done. There is no definite prognosis that applies to all children with this diagnosis.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

The Lissencephaly Network
Extensive website with medical information, parent articles, links to other sites and parent support.

Lissencephaly Contact Group
The best known website to operate from the UK, publishes a newsletter, links to other sites and information about ongoing research.

Google Search for Lissencephaly

References and Sources

The Lissencephaly Network www.lissencephaly.org Online Mendelian Inheritance in Man (OMIM) www3.ncbi.nlm.nih.gov/Omim/