Figure 9: Schematic diagram of agenesis of the corpus callosum without interhemispheric cyst. A coronal view (top left) shows that the lateral ventricles point superiorly. At the superior scan level (top right), both walls of the lateral ventricles are identified where only periventricular lines are normally present. The lower section (bottom right) shows dilatation of the occipital horns and separation of the frontal horns. The third ventricle may or may not be dilated.
A specific diagnosis of agenesis of the corpus callosum has seldom been made before the third trimester, probably because the corpus callosum is not normally formed until 18 to 20 weeks43. Most authors agree that detection of agenesis of the corpus callosum is difficult prenatally, depending as it does on postnatal sonograms or CT or MR scans. In a series of seven fetuses with agenesis of the corpus callosum, Bertino et al35 reported that only three demonstrated a characteristic midline cyst. They described three findings that might lead one to suspect agenesis of the corpus callosum on routine transverse views:
- disproportionate enlargement of the occipital horn,
- demonstration of both medial and lateral ventricular walls at a level where the single periventricular line is normally demonstrated, and
- a more parallel course of both ventricular walls than normal.
They suggested that demonstration of these findings on axial views should stimulate additional coronal and sagittal views for evaluation of agenesis of the corpus callosum.
The increased separation of the normal-sized bodies and the enlargement of the atria and occipital horns of the lateral ventricle result in a typical ultrasound image. Upward displacement of the third ventricle is a very specific sign36 but presents only in 40% of fetuses. Hilpert et al44 used transvaginal ultrasound and reported that the technique may be useful in identifying the intracranial structures and anomalies, especially in the late second and third trimester when the fetal head is presenting.
Recently, Byrd et al45 reported that MR is the best technique to evaluate the child or newborn with suspected agenesis of the corpus callosum and associated brain anomalies. They stated that CT and/or MR scans demonstrated the characteristic findings in agenesis of the corpus callosum with a slightly enlarged high-riding third ventricle interposed between the lateral ventricles. They could demonstrate Probst"s bundles in children with true agenesis, on a sagittal MR midline scan, which is the definitive radiological modality for evaluating agenesis of the corpus callosum.
The classic findings of agenesis of the corpus callosum on MR consist of lack of demonstration of the corpus callosum in all three anatomic planes with a third ventricle which is elevated and interposed between the lateral ventricles. The complete outline of the normal corpus callosum is always visible on the sagittal MR in infants and children, and a mistake in the diagnosis is seldom made.
Byrd et al45 found that ultrasound is a good screening modality of the neonatal head and can be used to demonstrate agenesis of the corpus callosum. When the findings are subtle on the ultrasound, or when agenesis of the corpus callosum is demonstrated on the ultrasonic examination, a CT or preferably an MR should be obtained to evaluate the brain for a complete outline of the corpus callosum and associated structures.
Pilu et al42 identified agenesis of the corpus callosum by prenatal ultrasound in 35 fetuses between 19 and 37 weeks. Findings included absent corpus callosum and cavum pellucidum, "teardrop" configuration of lateral ventricles, distended interhemispheric fissure, upward displacement of third ventricle, radiate arrangement of medial cerebral gyri, and abnormal branching of anterior cerebral artery. They identified associated anomalies in 20 fetuses, including anatomic defects and chromosomal abnormalities.
Other midline cystic masses such as arachnoid cyst, porencephaly, prominent cavum septum pellucidum31,33,36 may be mistaken for agenesis of the corpus callosum. All types of holoprosencephaly include agenesis of the corpus callosum as part of the underlying malformation, although alobar and semilobar holoprosencephaly should not be mistaken for agenesis of the corpus callosum alone. If a midline cyst is absent and dilatation of the atria and occipital horns is demonstrated, it may be mistaken for hydrocephalus. However, agenesis of the corpus callosum typically demonstrates greater enlargement of the occipital horns compared to the remaining ventricular system.
In an autopsy series of 47 cases of agenesis of the corpus callosum, Parrish et al14 reported that 85% of patients had other CNS anomalies, and 62% had extra-CNS anomalies. Associated CNS anomalies may include gyral anomalies, heterotopia, midline intracerebral lipomas, encephalocele, interhemispheric arachnoid cyst, microcephaly, Dandy-Walker malformation, Arnold-Chiari malformation, holoprosencephaly, hydrocephalus and aqueductal stenosis14,32.
Extra-CNS malformations may include anomalies of the face, musculoskeletal system, gastrointestinal tract, genitourinary tract, cardiovascular system, and respiratory system14.
The London Dysmorphology Database lists 108 syndromes in which agenesis of the corpus callosum is a feature46. Agenesis of the corpus callosum may be associated with a variety of other abnormalities in syndromes of Mendelian or unknown etiology, which are listed in Table 1. Others which are exceedingly rare or involve teratogen exposures are not included in this table.
|Table 1: Differential syndromic diagnosis for agenesis of corpus callosum.
||Seen by ultrasound
||Not seen by ultrasound
||short bones, oligodactyly
||inborn error of metabolism
|Basal cell nevus
||facial cleft/claw hand
||deafness, anal atresia
||tongue lobules, oliogodontia
||facial cleft, anophthalmia
||inborn error of metabolism
Agenesis of the corpus callosum has been associated with chromosome anomalies14,35,36,38 and translocations. In the largest prenatal series of fetuses with agenesis of the corpus callosum, Bertino et al35 reported a chromosome abnormality (trisomy 18) in one of seven fetuses (14%).
The corpus callosum is phylogenetically a recent structure, and its absence is not lethal. Isolated agenesis of the corpus callosum may be either a completely asymptomatic event (found incidentally) or revealed during the course of a neurologic examination by subtle deficits, such as inability to match stimuli using both hands or to discriminate differences in temperature, shape, and weight in objects placed in both hands16.
Persons with agenesis of the corpus callosum may have neurologic problems, such as seizures (60%), intellectual impairment (70%), and psychosis8,9,10. However, these conditions are believed to be caused by abnormalities in associated cerebral anomalies rather than in the corpus callosum per se. Hence, prognosis is determined primarily by the underlying or associated malformation(s)14. Studies of persons with isolated agenesis of the corpus callosum show that some have normal intelligence, while others are developmentally delayed28,48.
Grubben et al48 reported that three children they studied showed severe growth retardation of prenatal onset, hypotonia, and psychomotor retardation with notably impaired speech development. They also had hypotrophy of the distal extremities with small, puffy hands and feet.
Byrd et al45 studied a group of 105 children with a diagnosis of agenesis of the corpus callosum and reported that 26 (25%) had isolated agenesis of the corpus callosum with no associated brain anomalies. Eight of these presented with seizures which were controlled medically. Of the 105 children, 85% had symptoms and/or abnormal signs. The most common signs were macrocephaly with hydrocephalus and seizures. Postnatally, they found MR was the best radiological imaging modality for evaluating children with agenesis of the corpus callosum and associated brain anomalies. The most common associated brain anomalies (in decreasing frequency) were interhemispheric cyst with hydrocephalus, Dandy-Walker malformation, migrational disorder, absence of the inferior vermis, cephalocele, and lipoma of the interhemispheric fissure. The children who had the best prognosis without any significant neurologic sequelae were those with isolated agenesis of the corpus callosum.
The children with the worst prognosis and neurological sequelae were those with agenesis of the corpus callosum and migrational disorder with or without Dandy-Walker malformations45.
Pilu et al42 had follow-up data on 11 of the 20 patients they diagnosed prenatally. Two had IQ scores in the 70-85 range, while the other nine had scores above 85.
Identification of agenesis of the corpus callosum demands a careful search of fetal anatomy in its entirety. It is important to recognize that sonographic appearance of agenesis of the corpus callosum may be similar to that of uncomplicated hydrocephaly. A correct diagnosis is useful for guidance of appropriate and well-informed decision making. Diagnosis of isolated agenesis of the corpus callosum does not require any change in standard obstetrical management, but when multiple malformations are detected the optimum outcome may depend on special intervention. Amniocentesis is indicated.
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Originally published in The Fetus in 1994, posted 6/1999