Genes associated with MLIS Gene Location OMIM number RELN 7q22.1 CIT 12q24.23 NDE1 16p13.11 KATNB1 16q21 WDR62 19q13.12 ACTG1 17q25.3 TUBA1A 12q13.12 TUBB2B 6p25.2 TUBB3 16q24.3 TUBA3E 2q21.1 N/A TUBG1 17q21.2 DMRTA2 1p32.3 The genetic basis and pathophysiology of<unk>  are still not completely understood. Most cases of<unk>  are described in consanguineous families suggesting an autosomal recessive inheritance. Mutation of RELN gene or CIT could cause MLIS. Human NDE1 mutations and mouse Nde1 loss lead to cortical lamination deficits, which, together with reduced neuronal production cause<unk> . Homozygous frameshift mutations in NDE1 gene was found to cause<unk>  with up to 90% reduction in brain mass and seizures starting early in life. Some other disease-causing genes include: KATNB1 and WDR62. It is hypothesized that the KATNB1-associated<unk>  is the result of a combined effect of reduced neural progenitor populations and impaired interaction between the Katanin P80 subunit (encoded by KATNB1) and LIS1 ( PAFAH1B1), a protein mutated in type 1 lissencephaly. Missense mutation in ACTG1 gene was identified in three cases of<unk> . ACTG1 is the same gene that, when mutated, causes Baraitser-Winter syndrome. A loss-of-function mutation in the Doublesex- and Mab-3–Related Transcription factor A2 (DMRTA2, also known as DMRT5) gene has been reported in a case of<unk> , implicating DMRTA2 as a critical regulator of cortical neural progenitor cell dynamics. Microlissencepahly is considered a tubulinopathy (tubulin gene defect) i.e. is caused by mutation in tubulin genes, mainly TUBA1A and less commonly TUBB2B, TUBB3, TUBA3E and TUBG1. Central pachygyria, polymicrogyria are more commonly seen in patients with defects in TUBB2B, TUBB3, and TUBB5. This implys the critical role of microtubule cytoskeleton in the pathophysiology of<unk>  as well as other neuronal migration disorders. Congenital infections like cytomegalovirus are also known to cause<unk> . Both<unk>  and microcephaly with simplified gyral pattern result from either decreased stem cell proliferation or increased apoptosis in the germinal zone of the cerebral cortex.
Microlissencephaly
Microhydranencephaly
Schizencephaly
Hemihydranencephaly
Lissencephaly
Holoprosencephaly
Hydranencephaly
Megalencephaly