This is a study of a 23-year-old primigravida, who was referred to our clinic at 25 weeks of gestation because of fetal ventriculomegaly. On two-dimensional ultrasound (2D-US) in the axial view of the fetal head, findings such as an absent cavum septi pellucidi (Fig. 2c) and teardrop configuration of the lateral ventricles (Fig. 3a) with ventriculomegaly raised the suspicion of agenesis of the corpus callosum (ACC) (Fig. 3b). The Volume data sets of the brain were performed. The volume data set of the brain was stored and a retrospective offline analysis of the data was performed.
Complete ACC was diagnosed and it was confirmed (Figs 1 and 2d) by a postnatal computed tomographic scan (Fig. 3d). Fetal karyotyping revealed a normal (46XY) karyotype. A viable male infant with Apgars of 7 and 10 with birth weight of 2.9 kg was delivered at 39 weeks by elective cesarean section for breech presentation. The neurological examination of the newborn was normal.
We found 3D-US to provide a major contribution to the diagnosis and management of ACC. With its offline networking capabilities, it may improve healthcare delivery systems by extending the benefits of prenatal diagnosis and management of brain anomalies to poorly served areas where an MRI is not available.
Informed consent was obtained from the patient for publication of this case.
The corpus callosum (CC) is the main transverse tract of fibers that interconnects homologous territories of the two cerebral hemispheres, and it is responsible for the transfer of motor, sensorial, and cognitive information between the left and the right cerebral hemispheres 1. Anomalies of the CC can be classified into several subgroups: complete agenesis, partial agenesis, hypoplasia (thinning of the CC), and hyperplasia (thickening of the CC); these anomalies can occur as an isolated condition or as a complex condition in combination with other malformations 2. Both complete and partial callosal agenesis carry the title of agenesis of the corpus callosum (which is abbreviated as ACC or AgCC) 3.
In contrast, dysgenesis is a broad term used to describe the spectrum of callosal anomalies other than complete agenesis 4.
The CC is divided into four segments: the rostrum, the genu, the body, and the splenium. It develops during the 11th–20th weeks of fetal gestation. There have been two main theories regarding the progression of callosal development in utero; one theory suggests that callosal development begins with the genu and then continues posteriorly along the body to the selenium, the rostrum is the last part to be formed 1. The other theory proposes that callosal connections begin more centrally and the subsequent growth progresses bidirectionally both anteriorly and posteriorly 5.
By 18–20 weeks of gestation, the CC has assumed its final shape, and it continues to grow well after delivery 6.
The incidence of ACC varies as a function of both diagnostic techniques and the sample population.
The vast majority of studies cite the prevalence of ACC as 2–3% among people with developmental disabilities. It is much harder to estimate the incidence or prevalence rates for the nondisabled population because of a sample bias. Reasonable estimates place the incidence among the general population between 1.8 and 7/10 000 births 7.
To date, the exact cause of ACC is unknown; it can be inherited as either an autosomal recessive trait or an X-linked dominant trait. It can also be caused by an infection or injury during the 12th–22nd week of pregnancy, leading to developmental disturbance of the fetal brain. Intrauterine exposure to alcohol can also result in ACC 8.
Other potential causes of ACC are chromosomal abnormalities with an overall rate of 17.8%, including both isolated and complex ACC2. A recent study suggests that this high risk of chromosomal abnormalities is confined to complex cases 9. In addition, chromosomal microdeletions may be associated with ACC, and therefore, chromosomal analysis using comparative genomic hybridization should be considered in cases of ACC 2.
According to a recent study, the diagnosis of ACC could be made as early as 11–13 weeks 10, but an appropriate sonographic assessment can be performed only after 20 weeks 11.
The CC is assessed on US by direct visualization. The mid-sagittal views represent the gold standard for diagnosing abnormalities of the CC 11. Its visualization requires technical skill, and is not recommended in standard examinations of low-risk pregnant patients 12. However, it is possible to have a 3D mid-sagittal plane without having to visualize at this plane from a series of 2D images, which is of considerable value in cases of suboptimal fetal position where a sagittal plane is more difficult to achieve 12. ACC may be amenable to prenatal diagnosis on the basis of direct and indirect signs on prenatal US from 20 weeks onwards 13. Indirect signs include the absence of the cavum septi pellucidi (Fig. 2c) [it is usually present in partial ACC (pACC)], consequently it is occupied by three lines that are due to the widened interhemispheric fissure, centrally partitioned by the falx cerebri (Fig. 3b), ‘tearshaped’ appearance of the lateral ventricles the frontal horns of the lateral ventricles are further away than normal from the midline (laterally displaced) and the atria of the lateral ventricles slightly enlarged, an abnormal course of the pericallosal artery; in complete ACC, the semicircular loop of the pericallosal artery is lost and the branches of the anterior cerebral artery ascend linearly with a radiate arrangement (Fig. 4). The midline echo becomes a three-line complex due to increased separation of the hemispheres with a prominent interhemispheric fissure (Fig. 3b).
Also among the indirect signs are colpocephaly (dilatation of the atria and the occipital horns) (Fig. 3a) and increased distance between the frontal horns (arrows) with a characteristic aspect of a bull’s horn due to the medial compression exerted by the Probst (Fig. 3c) 2. However, a significant number of cases of ACC may escape diagnosis during the mid-trimester screening US as these indirect signs are absent or not clearly visible at that time. Furthermore, the transventricular screening view may appear normal in 43.5% of cases less than 24 gestational weeks in cases of pACC 14.
However, definite diagnosis of partial or complete agenesis necessitates the examination of the mid-sagittal plane of the brain, with the transducer parallel to the direction of the genu of the CC, which is the same as the profile view of the face with the transducer parallel to the nose.
In transabdominal scanning, acquisition of such a plane is often hindered by the position of the fetal head 15. With the 3D volume acquired in the axial plane and after reconstruction of the sagittal section (Fig. 2), it is possible to visualize the CC in 98% of cases 16.
One of the advantages of 3D ultrasonography is that it offers the potential of acquiring the volume of the fetal head in any position, and then, by reconstructing the image using the multiplanar technique the appropriate view of the CC can be obtained for examination 17.
Neurodevelopmental outcome in truly isolated ACC (MRI-confirmed ACC) is reported as normal outcome in about 75% of the cases 18,19. Children with agenesis of the CC may be entirely asymptomatic or associated with only mild developmental or behavioral deficits; mild learning difficulties are frequently observed 19,20. A recent systematic review 18 assessed the rate of neurodevelopmental outcome in 132 fetuses (16 studies) with isolated ACC. The authors reported neurodevelopmental outcome as: normal; borderline or moderate disability; or severe disability. In complete ACC, the respective figures were 74.3%, 14.3% and 11.4%, while for isolated partial ACC, they were 65.5%, 6.9% and 27.6%. When taking into account only those studies using MRI and standardized tools of neurodevelopmental assessment, in complete ACC, the rates were 83.7%, 8.2% and 8.2% for normal, borderline/moderate and severe disability, respectively. The corresponding rates for partial ACC were not reported due to the small number of cases. They found no statistically significant difference in outcome between fetuses with isolated complete ACC and those with isolated partial ACC 18. Normal outcome reaches 87.3 in cases of complete ACC (CACC), and severe disability is reported to be 11.4% in isolated ACC and 8.2% in MRI-confirmed isolated CACC 19. In other words, the rate of neurodevelopmental delay in infants with a prenatal diagnosis of isolated ACC is about 25%, and this appears to be similar in CACC and pACC 18. In contrast, the outcome of complex ACC is pathological in half of the cases and depends on the underlying pathology 21.
In addition, anomalies of the CC appear to play a role in language impairments in autism as a high percentage of individuals with ACC display many traits characteristic of individuals diagnosed with autism spectrum conditions. On the basis of these findings, structural causes such as ACC should be considered in the etiologic investigation of autism spectrum conditions 22.
ACC is a condition with a diverse spectrum of etiologies, presentations, and outcomes. It appears that 3D-US applications will make a significant contribution to our understanding of the developing fetal CC in both normal and anomalous cases, and we find that it does indeed provide useful information such as in this case. We suggest that 3D-US may be an integral part of the examination of fetuses referred for suspected ACC (Fig. 5).
Conflicts of interest
There are no conflicts of interest.
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