Unlocking the Mystery of Adult-Onset Chediak-Higashi Syndrome: A Comprehensive Guide to Genetic Testing

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Chediak-Higashi syndrome (CHS) is a rare genetic disorder that affects multiple systems in the body, including the immune system, skin, and nervous system. While CHS is typically diagnosed in childhood, adult-onset CHS is a less common and often underdiagnosed form of the condition. This article will explore the role of genetic testing in understanding, diagnosing, and managing adult-onset CHS, with a focus on the latest research and breakthroughs in the field.

Understanding Chediak-Higashi Syndrome

CHS is caused by mutations in the LYST gene, which is responsible for the production of a protein involved in the transport and sorting of cellular components. The disorder is characterized by a weakened immune system, increased susceptibility to infections, and the presence of large, abnormal lysosomes in various cell types. CHS can also cause albinism and neurological problems, such as seizures and cognitive impairments.

Adult-onset CHS is a rarer form of the condition, with patients often experiencing milder symptoms and a slower progression of the disease. However, diagnosing adult-onset CHS can be challenging due to its atypical presentation and the lack of awareness among healthcare professionals.

Diagnosing Chediak-Higashi Syndrome

Diagnosing CHS typically involves a combination of clinical examination, blood tests, and genetic testing. Blood tests can reveal characteristic features of CHS, such as abnormal white blood cells and reduced immune function. However, definitive diagnosis requires identification of the underlying genetic mutation through genetic testing.

Genetic Testing for CHS: cDNA Sequencing

A recent study titled “cDNA sequencing increases the molecular diagnostic yield in Chediak-Higashi syndrome” highlights the use of cDNA sequencing as a valuable tool for diagnosing CHS. This advanced genetic testing technique allows for the identification of mutations in the LYST gene, providing a definitive diagnosis and facilitating access to appropriate treatments and genetic counseling.

Mapping the CHS Gene: A Breakthrough in Understanding the Disorder

Research published in “Genetic and physical mapping of the Chediak-Higashi syndrome on chromosome 1q42-43” has successfully mapped the CHS locus to chromosome 1q42.1-q42.2. This breakthrough discovery confirms the hypothesis that the same gene defect causes CHS in humans and the beige phenotype in mice, paving the way for a deeper understanding of the disorder and the development of targeted treatments.

Case Studies Highlighting the Importance of Genetic Testing in Adult-Onset CHS

A Unique Case of CHS Triggered by SARS-CoV-2 Infection

A case report titled “Primary haemophagocytic lymphohistiocytosis (Chédiak-Higashi Syndrome) triggered by acute SARS-CoV-2 infection in a six-week-old infant” presents a unique instance of a 6-week-old infant diagnosed with CHS after primary HLH was triggered by a SARS-CoV-2 infection. This case highlights the importance of considering CHS in patients with unusual presentations and the role of genetic testing in confirming the diagnosis.

Atypical CHS Diagnosed Through Genetic Investigation

In a paper titled “La sindrome di Chediak-Higashi a esordio tardivo”, researchers describe a case of hypertrophic-hyperplastic gingivopathy associated with leuko-neutropenia, which led to the diagnosis of atypical CHS through genetic investigation. This case underscores the value of genetic testing in diagnosing adult-onset CHS, particularly when clinical presentation is atypical.

Conclusion

Genetic testing plays a crucial role in understanding, diagnosing, and managing adult-onset Chediak-Higashi syndrome. The advancements in genetic testing techniques, such as cDNA sequencing and gene mapping, have significantly improved the diagnostic yield and facilitated access to appropriate treatments and genetic counseling. As our understanding of CHS continues to grow, it is essential for healthcare professionals to consider the possibility of adult-onset CHS in atypical cases and utilize genetic testing to confirm the diagnosis.

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)