Decoding Periventricular Laminar Heterotopia: Embracing Genetic Testing for Better Understanding and Diagnosis

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Periventricular laminar heterotopia (PLH) is a rare neurological disorder characterized by the abnormal migration of neurons during fetal brain development. This results in the formation of nodules or masses of neurons along the walls of the lateral ventricles in the brain. These nodules can disrupt normal brain function and are often associated with epilepsy, developmental delays, and intellectual disabilities. In recent years, genetic testing has emerged as a powerful tool for understanding, diagnosing, and managing PLH.

Understanding the Genetic Basis of PLH

Several studies have shed light on the genetic underpinnings of PLH, highlighting the role of various genes and genomic imbalances in the development of the disorder. One such study found that rare genomic imbalances are a frequent cause of periventricular nodular heterotopia (PNH), a related condition. This research suggests that array comparative genomic hybridization (array-CGH) should be considered as a first-line diagnostic test for PLH.

Other studies have identified specific gene mutations associated with different forms of PLH. For example, a novel NEDD4L missense mutation was found to cause periventricular nodular heterotopia 7 (PVNH7), while a heterozygous variant of the NEDD4L gene was identified as the probable cause of disorders in a patient with PVNH7. Additionally, two pathogenic FLNA gene variants were reported as the genetic cause of periventricular nodular heterotopia and epileptic seizure in three patients.

Diagnosing PLH Through Genetic Testing

Given the growing understanding of the genetic basis of PLH, genetic testing has become an invaluable tool for diagnosing the disorder. Array-CGH, a high-resolution genome-wide scanning technique, can detect submicroscopic chromosomal imbalances and copy number variations (CNVs) that may be associated with PLH. This method has been recommended as a first-line diagnostic test for PLH, as it can identify rare genomic imbalances that may be the cause of the disorder.

Benefits of Genetic Testing for PLH

Genetic testing offers several advantages in the context of PLH:

• Accurate diagnosis: Identifying the specific genetic cause of PLH can help clinicians make a more accurate diagnosis, which is critical for determining the most appropriate treatment and management strategies.
• Early intervention: Genetic testing can be performed prenatally or in early childhood, allowing for early identification of PLH and the implementation of appropriate interventions to improve outcomes.
• Personalized treatment: Understanding the genetic basis of an individual’s PLH can help clinicians tailor treatment plans to address the specific needs and challenges associated with their particular genetic variant.
• Family planning: Genetic testing can provide valuable information for families affected by PLH, enabling them to make informed decisions about future pregnancies and the potential risk of passing the disorder on to their children.

Limitations of Genetic Testing for PLH

While genetic testing offers many benefits, it is important to recognize its limitations:

• Not all genetic causes are known: While several gene mutations and genomic imbalances have been associated with PLH, not all genetic causes of the disorder have been identified. As a result, genetic testing may not provide a definitive diagnosis for all individuals with PLH.
• False positives and negatives: As with any diagnostic test, there is a risk of false positives and negatives in genetic testing. This underscores the importance of interpreting genetic test results in the context of clinical findings and family history.
• Emotional and ethical considerations: Genetic testing can raise complex emotional and ethical issues for individuals and families affected by PLH. It is important for healthcare providers to discuss these issues with patients and provide appropriate support and counseling.

In conclusion, genetic testing is a powerful tool for understanding, diagnosing, and managing periventricular laminar heterotopia. By embracing this technology and continuing to expand our knowledge of the genetic basis of PLH, we can improve the lives of those affected by this rare and complex disorder.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)