The affected patients are mostly asymptomatic. Most of the patients present within the first two years of life.

Patients with agenesis of corpus callosum usually present with:

1. Mental retardation (60%)
2. Vision problems (33%)
3. Delay in the development of speech (29%)
4. Seizures (25%)
5. Feeding problems (20%)
6. Impaired hand-eye coordination and
7. Socio-behavioral disorders like attention-deficit-hyperactivity disorder (ADHD) and psychosis

Isolated agenesis of corpus callosum patients may have normal intelligence quotient, but may have some cognitive deficits which group under the "core syndrome" which includes[11]:

1. Reduced interhemispheric transfer of sensory-motor information
2. Reduced cognitive processing speed
3. Deficits in complex reasoning and novel problem-solving

Fetal ultrasound can detect agenesis of the corpus callosum as early as the 16th week of gestation.[2] But it is associated with a false-positive rate of 0% to 20%.[12]

An antenatal ultrasound scan may show some findings suggestive of agenesis of the corpus callosum:

1. Dilated and elevated third ventricle
2. Lateral ventricles may appear as widely spaced parallel bodies with small frontal horns
3. Colpocephaly gives rise to a "teardrop" configuration on axial scans.
4. Absent septum pellucidum with widened interhemispheric fissure
5. Color Doppler may show that the normal semicircular arterial loop, formed by the pericallosal artery, along with the superior surface of the corpus callosum, is missing or distorted

Magnetic resonance imaging of the brain is the investigation of choice for agenesis of the corpus callosum.

The following signs are suggestive of the diagnosis[13][14]:

1. Racing car sign: Axial imaging of the lateral ventricles will show the similarity to a Formula One car viewed from above
2. “Moose head appearance” or “Viking helmet sign” or "Longhorn appearance": Coronal views at the level of the frontal horns have this characteristic appearance due to CCA and eversion of bilateral cingulate gyri into the frontal horns
3. Sunray appearance: Sagittal imaging shows gyri radiating outward in a radial pattern from the ventricle
4. Lateral ventricles appear to be parallel to each other and non-converging
5. ACC is also typically accompanied by colpocephaly (dilatation of the trigones and occipital horns)
6. High riding third ventricle
7. Along the superomedial surface of lateral ventricles, inverted Probst bundles may be present

Neuropsychological evaluation of all patients with agenesis of the corpus callosum is mandatory.

Treatment is mainly symptomatic and supportive.

The mainline of treatment include:

1. Anti-epileptic medications
2. Special education
3. Physiotherapy
4. Ventriculoperitoneal shunt if hydrocephalus is present
5. Genetic counseling to family members
6. Surgeries for associated syndromic morphological abnormalities
7. Speech and visual rehabilitation
8. Psychological and psychiatric therapies as appropriate

The primary imaging differential diagnoses are holoprosencephaly and septo-optic dysplasia.

The main feature which helps to differentiate between the absence of septum pellucidum and agenesis of the corpus callosum is the presence of fused or communicating frontal horns and of the corpus callosum(which may sometimes appear thinned).

The presence of fused frontal horns, an abnormal anterior cerebral artery (azygos anterior cerebral artery), and absence of a normally developed interhemispheric fissure anteriorly in holoprosencephaly assist in differentiating it from isolated and complete agenesis of the corpus callosum.

Midline interhemispheric cysts may also be associated with agenesis of the corpus callosum. The differential diagnosis of such cysts are:

1. Cavum septum pellucidum
2. Cavum vergae
3. Cavum velum interpositum and
4. Interhemispheric arachnoid cyst

Sometimes these conditions can cause difficulty in diagnosis as a dilated third ventricle with a dorsal cyst can also appear the same. But the presence of choroid plexus in the roof of the third ventricle helps in differentiating the latter.

The prognosis is determined primarily by the associated malformations.

Agenesis of the corpus callosum is associated with the following intracranial anomalies (in decreasing order of frequency)[15]:

1. Interhemispheric cyst with hydrocephalus
2. Dandy-Walker malformation
3. Neuronal migration disorder
4. Agenesis of the inferior vermis
5. Encephalocele
6. Lipoma of the interhemispheric fissure

The children with isolated agenesis of the corpus callosum without any significant neurologic sequelae have the best prognosis.

The children with agenesis of corpus callosum associated with the neuronal migration disorder with or without Dandy-Walker malformation have the worst prognosis. 

Complications are more likely to occur due to the associated disorders. Some of these include:

1. Aspiration pneumonia
2. Seizures
3. Schizophrenia and
4. Cerebral palsy

Patients with developmental delay and intellectual disabilities may benefit from early intervention services, special education, and other supportive therapies.

An interprofessional approach involving the obstetrician for the antenatal care of the mother, neonatologist, pediatric neurologist, pediatric neurosurgeon, geneticist, maxillofacial surgeon, ophthalmologist, otorhinolaryngologist, plastic surgeon, pediatric psychiatrist and psychologist, dietician, and pediatric neuro nurse, working collaboratively in an interprofessional team approach can help to provide a good outcome for the patient with agenesis of the corpus callosum.