Name = Lissencephaly
DiseasesDB = 29492
ICD10 = ICD10|Q|04|3|q|00
ICD9 = ICD9|742.2
Lissencephaly, which literally means "smooth brain", is a rare brain formation disorder characterized by the lack of normal convolutions (folds) in the brain. It is caused by defective neuronal migration, the process in which nerve cells move from their place of origin to their permanent location. It is a form of
The surface of a normal brain is formed by a complex series of folds and grooves. The folds are called gyri or convolutions, and the grooves are called sulci. In children with lissencephaly, the normal convolutions are absent or only partly formed, making the surface of the brain smooth. Terms such as '
agyria' (no gyri) or ' pachygyria' (broad gyri) are used to describe the appearance of the surface of the brain.
Symptoms of the disorder may include unusual facial appearance, difficulty swallowing, failure to thrive, and severe psychomotor retardation. Anomalies of the hands,
fingers, or toes, muscle spasms, and seizures may also occur. Can sometimes be diagnosed in utero with MRI imaging, although this is not always reliable, or possible.
While a diagnosis of Lissencephaly is usually made at birth or soon after, CVS is currently available for some Lissecephaly gene variants prenatally. However for those remaining, the specific gene mutations have not yet been identified. No prenatal test is available for this group. Complex ultrasounds performed routinely during pregnancy may indicate the presence of cerebral abnormality, but this method of diagnosis is not reliable, and an absence of abnormal cerebral pathology should only inspire cautious optimism at best. Following the birth of an infant a diagnosis may be made or confirmed, by ultrasound,
computed tomography(CT), or magnetic resonance imaging(MRI).
Causes of lissencephaly can include viral infections of the uterus or the fetus during the first trimester, or insufficient blood supply to the fetal brain early in pregnancy. There are also a number of genetic causes of lissencephaly, including mutation of the
reelingene (on chromosome 7) [Hong SE, Shugart YY, Huang DT, Shahwan SA, Grant PE, Hourihane JO, Martin ND, Walsh CA. (2000) "Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations." Nat Genet. 26(1):93-6. PMID 10973257
] , as well as other genes on the
X chromosomeand on chromosome 17. Genetic counselingis usually offered if there is a risk of lissencephaly, and genetic testing, such as amniocentesis, can detect some, but not all lissencephaly mutations during pregnancy.
The spectrum of lissencephaly is only now becoming more defined as neuroimaging and
geneticshas provided more insights into migration disorders. There are around 20 different types of lissencephaly which make up the spectrum. Other causes which have not yet been identified are likely as well.
Different systems for classifying lissencephaly exist. One major distinction is "classic" (type I) vs. "cobblestone" (type II),cite journal |author=Forman MS, Squier W, Dobyns WB, Golden JA |title=Genotypically defined lissencephalies show distinct pathologies |journal=J. Neuropathol. Exp. Neurol. |volume=64 |issue=10 |pages=847–57 |year=2005 |month=October |pmid=16215456 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0022-3069&volume=64&issue=10&spage=847] but some systems add additional forms that fit into neither of these categories.
Some types of lissencephaly are described below (
OMIMnumbers are included where available):
Treatment for those with lissencephaly is symptomatic and depends on the severity and locations of the brain malformations. Supportive care may be needed to help with comfort and nursing needs. Seizures may be controlled with medication and hydrocephalus may require shunting. If feeding becomes difficult, a
gastrostomytube may be considered.
The prognosis for children with lissencephaly varies depending on the degree of brain malformation. Many individuals show no significant development beyond a 3- to 5-month-old level. Some may have near-normal development and intelligence. Many will die before the age of 2, but with modern medications and care, some children live into their teens. Respiratory problems are the most common causes of death.
* [http://www.lissencephaly.org The Lissencephaly Network]
* [http://www.lissencephaly.org.uk/aboutliss/ Lissencephaly.org.uk]
* [http://homepage.ntlworld.com/foliot/liss/ Lissencephaly Launch Pad (support)]
* [http://www.orpha.net/static/GB/lissencephaly_generic_term.html Lissencephaly, generic term] ( [http://www.orpha.net/data/patho/GB/uk-lissencephaly.pdf pdf document] ) - concise and thorough classification of lissencephaly by prof. Alan Verloes.
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