Comprehensive Prenatal Diagnosis and Care of Agenesis of the Corpus Callosum

Agenesis of the corpus callosum (ACC) is one of the most common referrals seen in the prenatal period at the Richard D. Wood Jr. Center for Fetal Diagnosis and Treatment (CFDT). The corpus callosum is the structure that connects the two hemispheres (left and right) of the brain. ACC is a heterogeneous condition resulting from disruption of multiple developmental steps. The reported prevalence is 1 in 4,000 to 5,000 live births; however, rates of 2% to 3% have been reported among patients with neurodevelopmental disabilities.

The cause of the disruption may be genetic, infectious (TORCH infections, Zika virus), vascular or toxic (fetal alcohol syndrome). Genetic factors are most common. Among the genetic causes, “syndromic” diagnosis is made in 30% to 45% of cases, and a monogenic cause can be identified in 20% to 35%. Over 200 genetic syndromes, many of which have variable phenotypes, include a disorder of the corpus callosum as a feature.

Some examples include:

• Anderman (ACC plus progressive neuropathy and dementia)
• MASA (L1CAM) (ACC plus hydrocephalus, adducted thumbs, intellectual disability)
• Aicardi (ACC plus chorioretinal lacunae, infantile spasms, intellectual disability)
• Acrocallosal (ACC plus polydactyly, craniofacial changes, intellectual disability)
• Vici (ACC plus albinism, recurrent infections, intellectual disability) syndromes

Chromosomal abnormalities are seen in approximately 18% of ACC, and include trisomy 18, trisomy 13 and mosaic 8.

We use a multidisciplinary team approach for prenatal counseling, including but not limited to fetal radiology (ultrasonography, fetal MRI, fetal ECHO), genetic counseling and consultation with a team of specialists such as maternal-fetal medicine/neurology/genetics/neonatology as indicated and other specialists based on any other associated malformations. Prenatal testing is discussed and offered with amniocentesis, maternal testing for cell-free DNA and infectious screening. The imaging and clinical history are discussed at our multidisciplinary fetal team meeting, and further diagnostic workup is planned accordingly.

ACC can occur as an isolated condition or in combination with other cerebral abnormalities, including Arnold-Chiari malformation, DandyWalker syndrome, schizencephaly (clefts or deep divisions in brain tissue), and holoprosencephaly (failure of the forebrain to divide into lobes). Girls may have a gender-specific condition called Aicardi syndrome, which causes severe cognitive impairment and developmental delays, seizures, abnormalities in the vertebra of the spine, and lesions on the retina of the eye. ACC can also be associated with malformations in other parts of the body, such as midline facial defects.

The effects of the disorder range from subtle or mild to severe, depending on associated brain abnormalities. Children with the most severe brain malformations may have intellectual impairment, seizures, hydrocephalus and spasticity. Other disorders of the corpus callosum include dysgenesis, in which the corpus callosum is developed in a malformed or incomplete way, and hypoplasia, in which the corpus callosum is thinner than usual. Individuals with these disorders have a higher risk of hearing deficits and cardiac abnormalities than individuals with the normal structure.

After the prenatal consultation and a plan for safe delivery of these infants, coordination is done with various specialists for long-term follow-up. Our team of fetal neurologists follows these infants over the long term to monitor their neurodevelopmental outcomes and offers multidisciplinary care along with a team of early intervention and developmental specialists.