Mini Review - (2024) Volume 8, Issue 2
Received: 01-Apr-2024, Manuscript No. Jcre-24-136705;
Editor assigned: 02-Apr-2024, Pre QC No. P-136705;
Reviewed: 16-Apr-2024, QC No. Q-136705;
Revised: 22-Apr-2024, Manuscript No. R-136705;
Published:
30-Apr-2024
, DOI: 10.37421/2795- 6172.2024.8.232
Citation: Nicoletti, Ferdinando. “Diversity in Phenotypic Manifestations Associated with Novel Doublecortin Gene Mutations in Subcortical Band Heterotopia.” J Clin Res 8 (2024): 232.
Copyright: © 2024 Nicoletti F. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Subcortical band heterotopia commonly known as double cortex syndrome, is a rare neurological disorder characterized by abnormal bands of gray matter beneath the cerebral cortex. This condition is primarily associated with mutations in the doublecortin gene, crucial for proper neuronal migration during brain development. Recent studies have highlighted the genetic basis of SBH and the diverse clinical presentations linked to new mutations in the DCX gene. This article explores the intricate relationship between genetic mutations and clinical phenotypes in SBH, emphasizing the evolving understanding of this neurodevelopmental disorder. SBH manifests a wide spectrum of neurological symptoms, ranging from mild cognitive impairments to severe epilepsy and developmental delay. Neuroimaging studies reveal variability in radiological features, reflecting differences in genetic mutations and developmental processes. While mutations in the DCX gene account for most SBH cases, genetic heterogeneity exists, with mutations in other genes also implicated. Understanding the clinical spectrum of SBH is crucial for accurate diagnosis, prognosis, and tailored management strategies, including genetic testing and neurodevelopmental interventions. In conclusion, SBH represents a complex disorder with significant phenotypic variability, influenced by mutations in the doublecortin gene and other genes involved in neuronal migration pathways. Further research into the genetic and molecular mechanisms underlying SBH is essential for developing targeted therapies and improving outcomes for affected individuals.
Doublecortin gene • Heterogeneity • Drug-resistant
Subcortical band heterotopia (SBH), also known as double cortex syndrome, is a rare neurological disorder characterized by the presence of abnormal bands of gray matter beneath the cerebral cortex. This condition is typically associated with mutations in the doublecortin (DCX) gene, which plays a critical role in neuronal migration during brain development. Recent studies have revealed a growing understanding of the genetic basis of SBH and the phenotypic variability associated with new mutations in the DCX gene. In this article, we explore the complex interplay between genetic mutations and clinical manifestations in SBH, shedding light on the evolving landscape of this neurodevelopmental disorder.
Subcortical band heterotopia is a disorder of neuronal migration, where neurons fail to reach their proper location in the developing brain, resulting in the formation of ectopic gray matter bands. These bands typically lie between the cortex and the ventricular zone, giving rise to the characteristic "double cortex" appearance on neuroimaging studies. SBH is often associated with epilepsy, intellectual disability, developmental delay, and other neurological symptoms, although the severity and clinical features can vary widely among affected individuals. The discovery of mutations in the doublecortin (DCX) gene provided a crucial link between genetics and the pathogenesis of SBH. The DCX gene encodes a protein involved in the regulation of microtubule dynamics and neuronal migration during brain development [1].
Mutations in the DCX gene disrupt normal neuronal migration, leading to the formation of subcortical bands and the clinical manifestations of SBH. While most cases of SBH are caused by mutations in the DCX gene, a small percentage of cases may be associated with mutations in other genes involved in neuronal migration pathways. The clinical spectrum of SBH ranges from mild intellectual disability and focal epilepsy to severe developmental delay and intractable epilepsy. Some individuals may be asymptomatic or have only mild cognitive impairments, while others may experience debilitating seizures and profound intellectual disability. Neuroimaging studies in SBH reveal a spectrum of radiological features, including the thickness and distribution of subcortical bands, the presence of associated brain abnormalities (e.g., cortical dysplasia, polymicrogyria), and the extent of cortical involvement. Variability in radiological features may reflect differences in the underlying genetic mutations and developmental processes. While mutations in the DCX gene are the most common cause of SBH, genetic heterogeneity exists, with mutations in other genes, such as LIS1 (PAFAH1B1), TUBA1A, and ARX, also implicated in some cases. The presence of different genetic mutations may contribute to phenotypic variability and clinical outcomes in SBH [2,3].
The phenotypic variability observed in SBH has important clinical implications for diagnosis, prognosis, and management. Genetic testing and neuroimaging studies play a crucial role in confirming the diagnosis of SBH, characterizing the extent of brain abnormalities, and identifying associated genetic mutations. Understanding the clinical spectrum of SBH helps clinicians tailor treatment strategies, including antiepileptic medications, neurodevelopmental interventions, and supportive care, to meet the individual needs of patients. Additionally, ongoing research into the underlying genetic mechanisms and pathophysiology of SBH holds promise for the development of targeted therapies aimed at mitigating symptoms and improving outcomes for affected individuals. Multidisciplinary collaboration among neurologists, geneticists, radiologists, and other healthcare professionals is essential for comprehensive management and optimal outcomes in patients with SBH. Furthermore, raising awareness about the condition among healthcare providers and the public can facilitate early detection, appropriate intervention, and improved quality of life for individuals living with SBH and their families [4-6].
Subcortical band heterotopia represents a complex neurodevelopmental disorder with significant phenotypic variability linked to mutations in the doublecortin gene and other genes involved in neuronal migration pathways. Advances in genetics and neuroimaging have deepened our understanding of the underlying mechanisms of SBH and expanded the clinical spectrum of this condition. Moving forward, further research into the genetic and molecular basis of SBH will be essential for unraveling the complexities of this disorder and developing targeted therapies to improve outcomes for affected individuals.
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Journal of Clinical Research received 11 citations as per Google Scholar report
