Nongenetic causes other than hypoxia or hypoperfusion mainly relate to congenital infections including CMV.141,144-146 There are a multitude of reports of PM’G in association with genetic factors, either as part of a known genetic disease or a multiple congenital anomaly syndrome, in association with a structural chromosomal abnormality, or in families with multiple affected members and/or Inhibitors,research,lifescience,medical consanguinity. There is an association of PMG with some metabolic diseases including Zellweger syndrome, although

the pathological changes differ from typical PMG.143,147,148 Zellweger syndrome has been found to be due to mutations in the PEX family of genes.149,150 Despite the longheld assumption that, most forms of PMG are the result of a nongenetic insult, familial cases and examples of PMG occurring in other genetic syndromes and structural chromosomal abnormalities are now abundant in the literature, Inhibitors,research,lifescience,medical as reviewed in Jansen and Andermann.151 All modes of inheritance have been suggested although an X-linked inheritance pattern appears most, frequent.152 The gene for bilateral frontoparietal PMG has been identified as GPR56, yet the function of this gene in cortical development is Inhibitors,research,lifescience,medical unclear.153 Our experience and recent data from the mouse suggest that the pathological changes have features in common with cobblestone cortical

malformation rather than typical PMG.154,155 Mutations in the gene SRPX2 have been found in one family with BPP,156 but. thus far mutations in this gene have not been reported in other

patients with BPP. PMG is also reported as a component, of several chromosomal deletion syndromes, particularly Inhibitors,research,lifescience,medical the 22q11.2 deletion syndromes such as the DiGeorge and velocardiofacial syndromes.157 Schizencephaly “Schizencephaly” (SCZ) is a term first used by Yakovlev and Wadsworth in 1946 to describe “true clefts formed in the brain as the result of failure of development of the cerebral mantle in the zones of cleavage of the primary cerebral fissures.”158,159 SCZ is differentiated from clefts Inhibitors,research,lifescience,medical in the cerebral mantle that arise as a consequence of destructive lesions, which Yakovlev and Wadsworth call “encephaloclastic porencephalies,” now known simply crotamiton as porencephaly. As part, of the definition of SCZ, the clefts must, be lined by abnormal gray matter described as “microgyria,” a term now synonymous with PMG. Macroscopically, the clefts of SCZ can be unilateral or bilateral and “openlipped” or “closed-lipped,” as shown in Figure 9 In openlipped clefts, the walls of the clefts do not buy Depsipeptide appose each other. In closed-lipped clefts the walls of the cleft are apposed and often fused, although a line of continuity between the lateral ventricle and subarachnoid space is usually visible (the “pia epcndymal seam158”). Clefts are frontal or parietal in approximately 65%, and temporal or occipital in approximately 35%.160 Other brain malformations may accompany SCZ.