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At a glance

It is a group of disorders that is associated with incomplete neuronal migration during the period of brain development at 9 to 24 weeks’ gestation. It is characterized by the absence of sulcation of the cerebral hemispheres resulting in smooth brain surface (absence of gyri). The name comes from the Greek lissos (smooth) and enkephale (brain). It involves the whole or parts of the surface of the brain. Clinically, it is characterized by microcephalia, severe psychomotor retardation, failure to thrive, intractable seizures, muscle spasticity, and hypotonia. The onset of the symptoms varies with age and the type of disorder. Life expectancy is often shortened due to respiratory complications.

Synonym

Agyria Syndrome.

Classification

The spectrum of lissencephaly with the advent of radiological technology and genetics is becoming more refined. There are around 20 types described on the basis of the brain surface appearance, ie, “classical” (Type I) and “cobblestone” (Type II). Type I is defined by an abnormally thickened brain surface in which only four rather than six cellular layers in the grey cortex are seen. Type II is characterized by severe brain malformations and associated obstructive hydrocephalus. Other types are added as they are distinct from the original classification and their mode of acquisition (ie, mutations/sporadically). They are listed as follows:

Type I

  • Miller-Dieker Syndrome (Miller-Dieker Lissencephaly Syndrome (MDLS), Chromosome 17p13.3 Deletion Syndrome): Characterized by multiple organ malformations (including congenital heart defects), severe intractable seizure, pre- and postnatal growth retardation, failure to thrive, and specific facial abnormality. The face, especially in children, presents a short nose with upturned nares, thickened upper lip with a thin vermilion upper border, frontal bossing, micrognathia, rotated and low ears, retrognathism of the midface, and hypertelorism. The forehead is prominent with bitemporal hollowing. Other features include polydactyly, abnormal palmar creases, and cataracts.

  • X-Linked Lissencephaly (Gene Located on Xp22.13): Medical condition fully expressed in males (hemizygotes). Females can also be affected (mutations). The clinical characteristics include an agenesis of the corpus callosum, severe seizures in infancy not responding to treatment, normal facial appearance, severe or profound intellectual disability, and failure to thrive. Life-threatening during infancy or early childhood.

  • X-Linked Lissencephaly with Ambiguous Genitalia: Condition that affects the normal development of the brain and is associated with genitalia malformations. The brain abnormalities include an agenesis of the corpus callosum that causes muscle spasticity, hypotonia, severe intellectual delay, and infantile epilepsy. Life expectancy is very short and most do not survive past the first decade of life. Clinically, the presence of a micropenis, cryptorchidism, and ambiguous genitalia particularly in female complete the clinical presentation. Its full genetic expression is seen only in males; however, mutations are suspected as it can also be seen in part in females.

  • Isolated Lissencephaly Sequence (ILS): Diagnosed at birth as newborns are affected with classical lissencephaly without underlying anomalies. The ...

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