Agyria pachygyriaband spectrum lissencephaly pachygyria agyria and subcortical band heterotopia

These are descriptive terms denoting abnormalities of cortical gyration, and are grouped together as they show an interconnected genetic basis. In all the gyration is simplified and the cortex is thickened. Lissencephaly (literally, smooth brain) is the most severe form, in which gyration is grossly diminished or even absent. Subcortical band heterotopia (subcortical laminar heterotopia, band heterotopia or double cortex syndrome) denotes the presence of a band of grey matter sandwiched by white matter below the cortical grey matter. The band may be thin or thick, and can merge with overlying cortex, in which case the cortex takes a macro-gryic form. When the bands are thin and clearly separated from the cortical ribbon, the ribbon itself may appear normal. Thicker bands are usually associated with macro-gyria, which refers to thickened cortex and can occur as an isolated phenomenon, is variable in extent and, when focal, is indistinguishable on clinical or imaging grounds from some forms of focal cortical dysplasia.

Most forms of lissencephaly occur without other non-cerebral malformations and are known as isolated lissence-phaly sequence (ILS). Isolated lissencephaly is present in 12 per million live births. The lissencephalic abnormality can affect the whole brain, resulting in profound retardation, epilepsy and spastic quadraparesis. Stillbirth can occur, and few patients survive beyond the age of 10 years. In less severe cases, where the lissencephaly is restricted to one region of the brain (albeit usually bilaterally, with an anterior or posterior gradient), the epilepsy and learning disability may be mild. Epilepsy presents before the age of 6 months in 75% of cases, as neonatal seizures or infantile spasms, and persists as multifocal and generalized types. Depth recording has shown discharges arising in the heterotopic tissue. The EEG shows characteristic high-amplitude fast activity. Of cases of isolated lissencephaly, 60 -80% are caused by identifiable mutations in the LIS1 or XLIS (also known as the DCX) genes, on 17p13.3 and Xq22.3-q24, respectively, and in 40% the entire gene is deleted. LIS1 lissencephaly is predominately posterior in location, and the condition occurs in both sexes and is sporadic. Conversely XLIS cases almost always occur in boys (X-linked dominant lissencephaly) and the brain anomaly tends to be anterior in location. Genetic testing is available for both forms. Typically, abnormalities of the DCX gene result in anteriorly predominant lissencephaly and LIS1 in posteriorly predominant lissencephaly. Anterior lissencephaly also occurs with abnormalities in the ARX gene and a range of phenotypes including West syndrome, dystonia and mental handicap. Posterior lissen-cephaly can be due to abnormalities in the RELN gene sometimes associated with cerebellar hypoplasia.

Other forms of lissencephaly have more widespread associations. The best known is the Miller-Dieker syndrome, which is caused by large deletions of LIS1 and of several other contiguous genes on 17p13.3 (e.g. 14-3-3E). In this syndrome lissencephaly is associated with epilepsy, facial dysmorphism, microcephaly, small mandible, failure to thrive, retarded motor development, dysphagia, and decorticate and decerebrate postures. Other organs, including the kidney and heart, may be affected. Survival varies from months to several decades, and epilepsy is usually profound and intractable. Genetic testing is available. Cobblestone lissencephaly (type 11) is found also in some patients with muscular dystrophy and ocular malformations.

Subcortical band heterotopia is caused in about 80% of cases by germline deletions in the DCX (XLIS) gene and almost always (but not exclusively) occurs in females. The pachygyria and bands are anteriorly predominant. The genetic anomaly in the other 20% of cases has not been identified. The rare cases of subcortical band heterotopia in boys are probably caused by mis-sense mutations in DCX or LIS1. Subcortical band heterotopia is a much more benign condition than lissencephaly. It can present in children or in adults, with epilepsy and learning disability. Epilepsy occurs in at least 80% of cases, and 50% of cases present with the Lennox-Gastaut phenotype. However, the manifestations of this anomaly can be slight, and occasional patients present with mild epilepsy and with normal intelligence. The clinical severity of the syndrome seems to correlate with the extent of the cerebral anomaly. In two-thirds of those with epilepsy, the seizures are intractable. Similarly, patients with pachygyria or macrogyria also have epilepsy and learning disability of variable severity, depending on the extent and location of the anomaly. The histological changes of lissencephaly, macrogyria, pachygyria and band hetero-topia may merge into one another, and in many patients these conditions represent a continuous spectrum rather than distinct entities. The anomalies are caused by abnormal cortical migration, and the factors influencing extent or severity have not been clearly identified. The cytoarchitecture varies, but in the Miller-Dieker syndrome, for instance, the lissen-cephalic cortex is thickened and has four rather than six layers (type I or classical lissencephaly). The changes can be regional and there may be associated dysplastic lesions.

Drug treatment follows conventional lines. Resective surgical therapy is not indicated, even where the bands or lissen-cephalic changes seems relatively localized, but callosotomy may help the occasional patients with frequent drop attacks.

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  • Katelyn
    What age is it to live with adulthood with lissencephaly in people?
    6 months ago

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