Lissencephalies
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Group of rare brain malformations, of varying severity, characterized by a defect in the brain convolutions (= smooth brain): one speaks of agyria (absence) and pachygyria (reduction) of the number of cortical gyrus. This disease is due to a disorder of cortical migration of neurons that occurs between the 12th and the 16th week of pregnancy.
Formerly:
- lissencephaly type I: conventional or
- lissencephaly type II: or cobblestone aspect.
Currently, based on their radiologic appearance (MRI) and the presence of associated brain abnormalities, one distinguishes 3 groups of lissencephaly :
1) classic lissencephaly
The cortex is too thick (10-15 mm instead of 4 mm) and poorly organized in four immature layers. Occasionally: expansion of the lateral ventricles or hypoplasia of the corpus callosum. A score of radiological gravity (known as Dobyns score, where rank 1 = diffuse agyria to 6 = subcortical laminar heterotopias)
in case of agyria: severe encephalopathy with early onset epilepsy resistant to pharmacological treatment (flexion spasms, typical EEG tracings), massive hypotonia, polyhandicap.
Sometimes associated with a malformative syndrome (e.g., Miller Dieker syndrome).
Subcortical laminar heterotopias: epilepsy which begins in the first decade of life and frequently progresses to type Lennox-Gastaut epilepsy and resisting to treatment: mental retardation of varying degrees (30 % of the patients are normal or "borderline"). Mutation of DCX gene. The most common form is in girls heterozygous for the mutation.
2) lissencephaly variants
a) X-linked lissencephaly with agenesis of the corpus callosum (XLAG): severe encephalopathy of the boy, neonatal seizures, micropenis and cryptorchidism, poor control of body temperature (hypothalamic dysfunction). Mutation of the ARX gene.
b) lissencephaly with cerebellar hypoplasia: 4 subgroups depending on the severity of the abnormalities of the cerebellum. Severe encephalopathy with hypotonia, ataxia, and sometimes epilepsy.
* LCHa: mildly severe cerebellar hypoplasia; mutations of the LIS1 or DCX genes
* LCHb: severe cerebellar hypoplasia (small, smooth, without foliation), mutation of the RELN gene
* LCHc: extreme microcephaly, severe cerebellar hypoplasia and other anomalies of the midline (cleft palate)
* LCHd: very severe microcephaly, diffuse cerebellar hypoplasia and involvement of the brainstem. Likely mutation of the TUBA1A genes.
c) lissencephaly with abnormalities of the basal ganglia: mutations in the genes encoding tubulin (TUBA1A)
Anesthetic implications:
depending on the specific type, mental retardation, epilepsy resistant to medical treatment, polyhandicap.
References :
- Saillour Y, Bahi-Buisson N.
Les lissencéphalies.
Neurone 2011 ; 16 : 34-40.
Updated: January 2019