Migration and to less extent organization develop during fetal life but are rarely diagnosed in low-risk populations due to late development of the sulcation or to the severity of associated malformations.
MCD’s caused by a mutation in a single gene can cause an extremely wide spectrum of disease ranging from mild neurological or developmental deficits to severe developmental delay, neuromotor impairment, intractable convulsions and even death during the first years of life.
An etiologic imaging diagnosis is usually difficult due to the fact that in some cases mutations in different genes produce similar signs.
Patients at high risk of abnormal neuronal migration disorders (Table 10–1) need a dedicated follow-up whenever possible in the context of the Fetal Neurology Clinic.
These patients should be, ideally, being followed by repeated neurosonographic examinations and whenever necessary fetal MRI.
The advancements in the field of next generation sequencing will become, in the near future, an essential part of the initial evaluation of these fetuses.
Table 10–1.PATIENTS AT HIGH RISK OF ABNORMAL NEURONAL MIGRATION ||Download (.pdf) Table 10–1. PATIENTS AT HIGH RISK OF ABNORMAL NEURONAL MIGRATION
Parents or siblings with MCD
Parents or siblings with non-diagnosed epilepsy
Maternal side siblings with MCD, epilepsy, early death of males
|Abnormal US findings
Ventriculomegaly (including mild)
Suspected microcephaly or macrocephaly
Agenesis of the septum pellucidum
Migration and organization disorders include diseases in which the neurons and glia cells are formed normally or almost normally but they fail to migrate or they migrate to abnormal spots in the brain without the formation of a six-layer cortex. Organization disorders refer to the abnormal formation of the connections between neurons due to intrinsic or extrinsic factors.
The diagnosis of migration and organization disorders in children and adults is difficult due to several reasons, including but not limited to the complexity of these diseases,1–3 the fact that their phenotypes are rarely exactly similar,2 and that different genes can present with similar imaging and clinical findings.4
These problems are even more serious when trying to reach a diagnosis in the fetus where we lack the clinical picture, and an incorrect diagnosis can affect not only the fetus but the whole family, including unborn siblings.
Ultrasound screening for the detection of fetal anomalies mainly, but not only, during the second trimester is performed routinely in many countries around the world,5 and includes the transabdominal demonstration of three axial planes of the brain.5–7 Using this approach and measuring only the lateral ventricle width and the size of the cisterna magna, Filly et al retrospectively found that they were able to recognize 109 out of 112 fetuses with prenatally diagnosed brain anomalies; in this study the authors did ...