Agenesis of the corpus callosum is either complete or limited to the posterior portion; the anatomy is variable but in the complete form the cavum septum pellucidi is not present; in the partial form, findings are more subtle and diagnosis requires direct visualization of the incomplete corpus callosum. The prognosis is largely influenced by the association with other anomalies; isolated agenesis of the corpus callosum may be associated with a normal intellectual development, although the experience is limited.
Agenesis of the septum pellucidum is frequently a part of other often severe malformations including holoprosencephaly, gross hydrocephalus, and schizencephaly. Isolated agenesis of the septum pellucidum may be a normal variant, although it may be the only antenatal finding of septo-optic dysplasia, a condition that is usually associated with visual impairment and endocrine dysfunction.
AGENESIS OF THE CORPUS CALLOSUM
Agenesis of the corpus callosum (ACC) is complete or partial absence of the corpus callosum. The corpus callosum is the biggest commissure connecting the hemispheres and is composed of axonal tracts connecting between the right and left side of the brain. It develops relatively late in pregnancy, at around 13 weeks, and continues growing well after delivery.
The incidence varies in different studies, depending upon the population investigated and the method of ascertainment. Estimates of 0.3% to 0.7% in the general population1,2 and 2% to 3% in the developmentally disabled are usually quoted.3 In our own experience with low-risk patients, assessed by ultrasound (US) at 15 to 17 weeks and reassessed at 22 to 25 weeks, we found only one case of ACC out of 2835 examinations.
ACC is heterogenous. Genetic conditions are probably the predominant etiology.4 Autosomal dominant,5 autosomal recessive,6,7 and sex-linked transmission8 as well as chromosomal anomalies including autosomal trisomies and other rearrangements9 have been described as causative factors. The recent introduction of chromosomal microarray and exome sequencing opened the way for a more precise determination of genetic conditions associated with fetal structural defects,10 cerebral anomalies,11 and isolated commissural anomalies.12 Recently Heide et al13 reported on 65 fetuses with callosal anomalies that underwent microarray and exome sequencing; a pathogenic copy number variant was identified in 3 cases (4.5%) and a pathogenic single-nucleotide variant in 12 cases (18%). Overall, the authors were able to determine a genetic etiology in 23% of cases.
Various teratogens have also been implicated as a possible cause of ACC, including alcohol and maternal phenylketonuria. It is important to remember that congenital callosal pathologies may also develop after prenatal insults such as infections14 or ischemic processes.15 Syndromes featuring callosal anomalies are presented in Table 8–1.