Variant lissencephalies: describes conditions associated with classical lissencephaly, but also additional distinguishing abnormalities, like severe cerebellar hypoplasia (lissencephaly with cerebellar hypoplasia; LCH) or absence of the corpus callosum (lissencephaly with agenesis of the corpus callosum; LACC). Autosomal recessive inheritance has been reported. Mutations in the RELN and VLDLR genes have been found in a few families with LCH.

X-linked lissencephaly: with abnormal genitalia: this condition only affects males and is characterised by lissencephaly, absence of the corpus callosum and small basal ganglia associated with underdeveloped genitalia. The prognosis is poor. Mutations in the ARX gene have been identified.

Periventricular nodular heterotopia (PVNH): this condition is also a neuronal migration disorder. Nerve cells, which have failed to migrate to the cortex, line the ventricle in a nodular fashion. Mutations in the FLNA gene on the X-chromosome have been predominantly identified in women with PVNH. An autosomal recessive form of PVNH has been associated with mutations in ARFGEF2.

Polymicrogyria (PMG): this may also be a neuronal migration disorder, but the exact nature of the condition is unclear. It is likely to be more common than lissencephaly. PMG is characterised by more frequent and smaller convolutions on the surface of the brain. It often appears in distinct patterns, and the most common is perisylvian polymicrogyria. Intrauterine infection (cytomegalovirus - CMV) is a known cause for PMG; intrauterine hypoperfusion has also been implicated. Familial occurrences and association with a number of different chromosome anomalies also point to a genetic aetiology in some cases. PMG is associated with a number of different chromosome anomalies; 22q11 deletions are the most common. A rare form of PMG has been associated with mutations in the GPR56 gene; causes for a number of syndromes with PMG as a feature have also been identified (see entries Goldberg Shprintzen syndrome, Joubert syndrome).

Schizencephaly (SCH): this describes a cleft from the cerebral cortex to ventricle, usually lined with polymicrogyria. The causes for SCH are thought to be similar to PMG; familial occurrences appear uncommon.

Congenital microcephaly and cortical malformations: lissencephaly, polymicrogyria, or simplified (not fully formed) gyri (SG) can also be seen in association with severe congenital microcephaly (very, very small head at birth). In these conditions autosomal recessive inheritance has been observed. The general term 'microlissencephaly' is often used, but is unfortunately inadequate to describe the variation in cortical anomalies mentioned above (like PMG and SG).

Inheritance patterns
Although the inheritance pattern is well established in some of the conditions described above, counselling in individual cases depends on the precise diagnosis, family history and laboratory investigations where available.

Classical lissencephaly/subcortical band heterotopia is commonly caused by deletions/mutations of the *LIS1 *gene on chromosome 17p, or the DCX gene on the X-chromosome. Recently mutations in the TUBA1A gene have been identified in some patients.

The inheritance observed in cobblestone lissencephaly and associated syndromes is autosomal recessive. WWS has been associated with mutations in the POMT1, POMT2 and FKRP genes, MEB with mutations in the POMGnT1 gene, and FCMD with mutations in the Fukutin gene.

Prenatal diagnosis
Prenatal diagnosis using molecular (genetic) tests is available in some cases. In certain circumstances ultrasound or MRI investigations during pregnancy may be helpful.

There is currently no support group for cortical malformations in the UK. Families can chat to other families online in our online community.