Lissencephaly is a rare genetic condition that presents the absence of normal folds in the region of the brain known as the cerebral cortex. Also known as the smooth brain, the children at birth may have the normal sized head. However, when infants are born with the reduced head size, they are diagnosed as microlissencephaly. This condition develops as the result of the defective neuronal migration during the development of the embryo, where the nerve cells migrate from their place of origin to the permanent location within the cerebral cortex grey matter. Lissencephaly can also occur in association with other conditions such as Miller-Dieker syndrome, isolated Lissencephaly sequence and Walker-Warburg syndrome. Most of the children with this condition die before the age of 10 years usually from severe seizures, respiratory disease or aspiration of food and fluids.
Causes
Lissencephaly can develop from the result of various genetic and non-genetic factors which can include intrauterine infection, insufficient supply of oxygen to the brain of the developing fetus or from the deletion or alteration of a part on chromosome 17. The genetic mutations in two different genes known as LIS1 on chromosome 17 or XLIS of chromosome X have been identified. Among some of the cases, it can develop as the result of mutations or small deletions of the LIS1 gene that is important for the production of a protein that plays various essential roles for the development of the outer region of the brain. The XLIS gene is important for the production of a protein that is needed for the normal neuronal migration. In some cases, this genetic mutation can develop randomly without its prevalence in the affected family or in other cases it can be inherited as an X-linked trait. The X-linked inheritance occurs when the genetic mutation is present on one of the sex chromosome (X chromosome). As males only inherit a single X chromosome, they are more likely to exhibit the features associated with the disorder and can be severely affected.
Symptoms
Infants born without underlying syndromes but present this condition are said to have isolated Lissencephaly sequence which can be the result of a mutation in the LIS1 gene. In addition to Lissencephaly, affected infants may present brain malformations, unusually small sized head, profound intellectual disability and seizures. Additional symptoms can include feeding difficulties, increased muscle tone later in life and diminished muscle tone early in life, growth failure and impaired motor abilities. These children are also at increased risk of developing life-threatening complications.
Diagnosis
The diagnosis of this condition is possible before the birth of the infant with specialized tests such as chorionic villus that removes a part of the placenta or amniocentesis that takes a sample of the fluid around the fetus. These samples will be studied to determine whether deletion of material from the chromosome 17 is evident. The classical Lissencephaly can be diagnosed based on the evaluation of diagnostic tests such as CT scan, MRI imaging, EEG, DNA and chromosomal analysis.
Treatment
There is no cure for this disease although the affected children can progress in their development with time. In the case of seizures, anticonvulsant medications can be helpful. The progressive hydrocephalus, a condition when the cerebrospinal fluid accumulates in the brain, may require shunting. Children presenting feeding difficulties may need gastrostomy tube. Additional supportive care may be beneficial for the affected children with feeding and nursing needs.
References
https://rarediseases.org/rare-diseases/lissencephaly/
https://www.ninds.nih.gov/Disorders/All-Disorders/Lissencephaly-Information-Page
