Lissencephaly
Incidence
Rare syndrome. 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. The incidence of all forms of type I lissencephaly is around 1 in 100,000 births. Update 2017 by MGJM.
Clinical Characteristics
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. 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. 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. The prognosis of children with lissencephaly depends on the type, the severity, and the response to treatment.
Precipitants
None
Provocation Tests
None
Diagnostic Procedures
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.