Decoding Simplified Gyral Pattern: A Guide to Understanding, Diagnosing, and Using Genetic Testing

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Understanding Simplified Gyral Pattern

Simplified gyral pattern (SGP) is a rare neurodevelopmental disorder characterized by microcephaly, a condition where the head circumference is significantly smaller than normal, and abnormal brain development. This disorder often presents with additional symptoms such as epilepsy, developmental delays, and intellectual disabilities. Recent studies have highlighted the importance of genetic testing in identifying the underlying causes of SGP and helping to guide treatment and management strategies for affected individuals and their families.

Diagnosing Simplified Gyral Pattern

Diagnosing SGP typically involves a combination of clinical evaluations, imaging studies, and genetic testing. Prenatal imaging can help identify cases of microcephaly with simplified gyral pattern, which can be useful for guiding prenatal counseling and diagnosis2. After birth, further imaging studies such as magnetic resonance imaging (MRI) can provide more detailed information about brain abnormalities and help confirm the diagnosis.

Using Genetic Testing for Simplified Gyral Pattern

Genetic testing plays a crucial role in diagnosing and understanding SGP. Various studies have identified specific gene mutations associated with this disorder, which can be detected through genetic testing methods such as whole exome sequencing (WES)1. Identifying these mutations can provide valuable information about the cause of the disorder and help guide treatment and management strategies.

Identifying Novel Genes and Reclassifying Diagnoses

Whole exome sequencing has proven to be a powerful tool in identifying novel genes associated with pediatric-onset neurodevelopmental diseases, including SGP1. This method allows for the analysis of all protein-coding genes in the human genome, making it possible to identify previously unknown genetic causes of SGP. By identifying these novel genes, clinicians can reclassify diagnoses and provide more accurate information to patients and their families.

Understanding the Role of Specific Gene Mutations

Several studies have identified specific gene mutations associated with SGP, such as homozygous mutations in the IER3IP1 gene3 and biallelic RTTN variants4. Understanding the role of these mutations in the development of SGP can help guide treatment and management strategies for affected individuals. For example, a homozygous IER3IP1 mutation has been associated with microcephaly, epilepsy, and permanent neonatal diabetes syndrome (MEDS), suggesting an overlap with Wolcott-Rallison syndrome3. Identifying these mutations can help clinicians better understand the specific genetic causes of SGP and provide more targeted treatment options.

Assessing Variant Pathogenicity

Genetic testing can also be used to assess the pathogenicity of identified gene variants. In one study, researchers used primary cilia length and number to determine the pathogenicity of biallelic RTTN variants identified in an infant with microcephaly, simplified gyral pattern, pontocerebellar hypoplasia, and seizures4. By assessing the functional impact of these variants, clinicians can better understand their role in the development of SGP and guide treatment and management strategies accordingly.

Conclusion

Genetic testing plays a vital role in understanding, diagnosing, and managing simplified gyral pattern. By identifying novel genes, understanding the role of specific gene mutations, and assessing variant pathogenicity, genetic testing can provide valuable information to guide treatment and management strategies for affected individuals and their families. As research continues to uncover the genetic basis of SGP, genetic testing will remain an essential tool in the diagnosis and management of this rare neurodevelopmental 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)