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Key Points

  1. Neuronal proliferation, migration and organization start relatively late in pregnancy and do not end until after delivery.

  2. In the absence of associated malformations, microcephaly and macrocephaly are rarely diagnosed before birth or even in the newborn.

  3. The majority of fetuses with a head circumference between -2 and -3SD will develop normally.

  4. When a suspicion is raised genetic and pediatric neurology consultations are indicated. In low-risk patients, these signs may represent the only possibility for prenatal diagnosis.

  5. Exomic sequencing if available must be considered if chromosomal microarray is normal or inconclusive.


The processes of primary neurulation and ventral induction that result in the formation of the neural tube and the formation of the prosencephalon respectively are completed by the second month of gestation.1 This is followed by three overlapping phases of cortical development that are under the control of numerous genes: proliferation, migration, and organization. Stem cells at the surface of the ventricles proliferate and divide into glial cells and neuronal cells. The glial cells migrate to the cortex in a very regular radial pattern, leaving a radial scaffolding along which the neurons migrate (radial migration) to the surface. The later-arriving neurons migrate in stages through the inner layers and ultimately lie outside them (inside-out migration). Ultimately, six layers are formed. Once the neurons arrive at the cortex, they organize local connections. In addition to this radial migration, there is also a tangential migration of neurons to form what are believed to be controlling tracts.2 The genes that control neuronal development also function in other parts of the body, so it is not unusual to find cerebral malformations associated with diverse somatic manifestations such as skeletal dysplasia as present in thanatophoric dysplasia. This normal orderly developmental process can be disturbed by genetic, teratogenic, or environmental conditions. Since the cerebrum develops simultaneously with other structures, an insult at a specific time can affect the normal development of all the structures that are vulnerable at that time, including eyes, face, hindbrain, and others, hence the importance of assessing all of these areas if abnormality is suspected in any one of them. During the last decade, the knowledge regarding the genetics, morphology, and clinical aspects of these conditions has expanded significantly, and new developments in this field occur rapidly.

Different classifications of malformations of cortical development (MCD) have been proposed3–6 (Table 9–1). Fundamentally, they are based on two factors: gene abnormality, and timing of the first abnormal developmental event. Final phenotypic outcomes are often more dependent on the time that an insult occurs and interferes with normal development than its specific nature. Although Barkovich and Volpe’s classifications3,5,7 are particularly useful in clinical management, they are acknowledged to be in evolution and are changing as new information becomes available.8,9 Sarnat’s classification4 is more centered on the genetic ...

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