Overview of Congenital Neurologic Anomalies

Congenital brain anomalies cause a spectrum of neurologic deficits; although some may cause no clinically significant effects, others may be fatal.

Some of the most serious neurologic anomalies (eg, anencephaly, encephalocele, spina bifida) develop in the first 2 months of gestation and represent defects in neural tube formation (dysraphism). Others, such as lissencephaly, result from problems with neuronal migration (see Malformed Cerebral Hemispheres), which occurs between 9 weeks and 24 weeks of gestation. Hydranencephaly and porencephaly are secondary to destructive processes that occur after the basic architecture of the brain has formed. Some anomalies (eg, meningocele) may be relatively benign.

There are many causes of congenital brain anomalies, including many still unknown genetic factors. Next-generation sequencing techniques, such as genetic panels and whole exome sequencing, have revealed a large number of genetic causes of these anomalies.

Prenatal ultrasound can screen for major brain malformations in utero. Fetal MRI techniques are increasingly useful, mainly when ultrasound findings are of concern. Genetic causes are typically not discerned prenatally. Fetal genetic testing can be performed via maternal cell-free DNA testing, chorionic villous sampling, or amniocentesis. Karyotyping can identify large chromosomal rearrangements and copy number variants. Advanced genetic testing options to detect gene mutations that cause some cortical malformation syndromes, such as somatic mutations, are limited.

When a congenital neurologic anomaly is detected, parents should be counseled about the impacts of the malformation on a child and be offered psychological support, if appropriate. Genetic counseling should be offered and genetic testing of the parent and child should be considered because the recurrence risk of a related malformation may be as high as 25 to 50%, depending on the inheritance pattern.