Unlocking the Mysteries of Chediak-Higashi Syndrome: A Comprehensive Guide to Understanding, Diagnosing, and 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, nervous system, and pigmentation of the skin, hair, and eyes. The childhood type of CHS is characterized by recurrent infections, neurological dysfunction, and partial albinism. Early diagnosis and genetic testing play a crucial role in the management and prognosis of this disease. In this article, we delve into the complexities of CHS, examining the latest research on understanding, diagnosing, and using genetic testing for this rare condition.

Understanding Chediak-Higashi Syndrome

CHS is caused by mutations in the LYST gene, which is involved in the formation and function of lysosomes, cellular structures responsible for breaking down and recycling waste materials. The mutations lead to the formation of abnormally large lysosomes, impairing the normal function of cells and resulting in the various symptoms associated with the syndrome.

Although CHS is a rare condition, recent research has shed light on novel variants of the disease. A study published in the Annals of Clinical and Translational Neurology describes a case of late-onset CHS with progressive gait ataxia, spastic paralysis, cognitive dysfunction, and peripheral neuropathy, but without immunological abnormalities or skin depigmentation. This case highlights the importance of considering CHS in the differential diagnosis of patients presenting with atypical symptoms.

Diagnosing Chediak-Higashi Syndrome

Diagnosing CHS can be challenging due to its rarity and the variability of its clinical presentation. A combination of clinical findings, laboratory tests, and genetic analysis is often required to confirm the diagnosis. A recent article published in the Indian Journal of Hematology and Blood Transfusion emphasizes the importance of morphology in diagnosing CHS, even in the era of molecular biology.

In this case report, the authors describe a young patient with CHS who presented with fever, hepatosplenomegaly, and pancytopenia. The diagnosis was confirmed by observing the characteristic giant granules in the patient’s white blood cells, a finding that underscores the continuing relevance of morphology in the diagnostic process.

Genetic Testing for Chediak-Higashi Syndrome

Genetic testing is an essential tool in the diagnosis and management of CHS. Identifying the specific mutation in the LYST gene not only confirms the diagnosis but also provides valuable information for genetic counseling and potential future treatments.

Improving Molecular Diagnostic Yield

A study published in Frontiers in Genetics demonstrates the benefits of using complementary DNA (cDNA) sequencing alongside genomic DNA (gDNA) Sanger sequencing to increase the molecular diagnostic yield in CHS patients. The researchers identified novel mutations in the LYST gene that would have been missed by gDNA sequencing alone, highlighting the importance of using multiple genetic testing techniques to improve diagnostic accuracy.

Genetic Testing in Atypical Cases

Genetic testing can also be helpful in diagnosing atypical cases of CHS, such as the case described in the British Journal of Haematology. In this report, a 6-week-old infant presented with primary haemophagocytic lymphohistiocytosis triggered by SARS-CoV-2 infection and was later diagnosed with CHS through genetic testing. This case illustrates the importance of considering CHS in the differential diagnosis of infants with severe infections and the utility of genetic testing in confirming the diagnosis.

Conclusion

Chediak-Higashi syndrome is a rare but complex genetic disorder with a wide range of clinical presentations. Understanding the underlying genetic mutations, the importance of morphology in diagnosis, and the benefits of genetic testing are crucial in managing this condition. As research continues to shed light on the intricacies of CHS, we move closer to providing better care and improved outcomes for those affected by this challenging disease.

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)