Corpus Callosum Agenesis: An Insight into the Etiology and Spectrum of Symptoms

Abstract

Brain hemispheres are connected by commissural structures, which consist of white matter fiber tracts that spread excitatory stimuli to various regions of the cortex. This allows an interaction between the two cerebral halves. The largest commissure is the corpus callosum (CC) which is located inferior to the longitudinal fissure, serving as its lower border. Sometimes this structure is not completely developed, which results in the condition known as agenesis of the corpus callosum (ACC). The aim of this paper was to review the latest discoveries related to the genetic and metabolic background of ACC, including the genotype/phenotype correlations as well as the clinical and imaging symptomatology. Due to various factors, including genetic defects and metabolic diseases, the development of CC may be impaired in many ways, which results in complete or partial ACC. This creates several clinical implications, depending on the specificity of the malformation and other defects in patients. Epilepsy, motor impairment and intellectual disability are the most prevalent. However, an asymptomatic course of the disease is even more common. ACC presents with characteristic images on ultrasound and magnetic resonance imaging (MRI).

Expanding the clinical phenotype of the ultra‐rare Skraban‐Deardorff syndrome: Two novel individuals with WDR26 loss‐of‐function variants and a literature review

“…Surprisingly, our patients showed remarkable muscle strength and often hypertonia; hypertonic limbs with brisk reflexes were also previously reported for one case (Skraban et al, 2017). We can speculate that this ambiguous muscle tone phenotype, as well as the diverse type of walking, could be related to the brain MRI findings, predominantly affecting the white matter such as corpus callosum anomalies (Edwards et al, 2014; Hofman et al, 2020), enlarged ventricles, white matter volume loss, and mild cerebellar hypoplasia (Skraban et al, 2017). Furthermore, the combination of wide‐based gait and spastic and/or stiff‐leg gait are often reported.…”

Unique variants in CLCN3, encoding an endosomal anion/proton exchanger, underlie a spectrum of neurodevelopmental disorders

“…17,38,39 Partial or full agenesis of the corpus callosum (ACC [MIM: 217990]) was also present in five of the individuals and is a common malformation with diverse etiology, including variants in >20 genes. 40 In these genetic disorders, ACC is often variable and its expression may differ between mice and humans. For instance, in ACCPN (peripheral neuropathy with agenesis of the corpus callosum, or Anderman syndrome [MIM: 218000]), which is caused by loss-of-function variants in SLC12A6 encoding the K þ -Cl À -cotransporter KCC3, 41 penetrance is incomplete in humans and preliminary studies in Kcc3 À/À mice indicated that they have a normal corpus callosum.…”

Role of prenatal magnetic resonance imaging in fetuses with isolated anomalies of corpus callosum: multinational study

“…Anomalies of the corpus callosum (CC) are among the most common central nervous system (CNS) malformations diagnosed during the fetal period [1][2][3][4][5] . These anomalies present commonly in association with other CNS and extra-CNS anomalies, aneuploidies or genetic syndromes and carry a high risk of adverse neurodevelopmental outcome [6][7][8] .…”