Expert Reviewed By: Dr. Brandon Colby MD
Chromosome breakage syndromes are a group of genetic disorders characterized by chromosomal instability and an increased risk of cancer. One such rare autosomal recessive disorder is Nijmegen Breakage Syndrome (NBS), which manifests as lung damage, immunodeficiency, and microcephaly. In this article, we will explore the current understanding of NBS, its diagnosis, and the role of genetic testing in managing this complex disease.
Understanding Nijmegen Breakage Syndrome
NBS is a rare genetic disorder caused by mutations in the NBN gene, which is responsible for producing the nibrin protein. Nibrin plays a crucial role in repairing damaged DNA and maintaining genomic stability. When the NBN gene is mutated, it leads to impaired DNA repair and increased genomic instability, resulting in the characteristic features of NBS, such as microcephaly, immunodeficiency, and lung damage (source).
Microcephaly and NBS
Microcephaly, or a smaller than normal head size, is one of the hallmark features of NBS. A recent study using induced pluripotent stem cell-derived brain organoids found that impaired p53-mediated DNA damage response contributes to microcephaly in NBS patients (source). This finding provides valuable insight into the mechanisms underlying this aspect of the disease and may help guide future therapeutic approaches.
Immunodeficiency and NBS
NBS patients often suffer from immunodeficiency, which makes them susceptible to recurrent infections. The immunodeficiency in NBS is primarily due to abnormalities in the development and function of immune cells, particularly B and T lymphocytes (source).
Lung Damage and NBS
A retrospective study focusing on pulmonary manifestations of NBS found that patients often present with recurrent respiratory infections, bronchiectasis, and interstitial lung disease (source). These lung complications further contribute to the morbidity and mortality associated with NBS.
Diagnosing Nijmegen Breakage Syndrome
Diagnosing NBS can be challenging due to the rarity of the disease and the variability in its clinical presentation. The diagnosis is typically based on clinical features, such as microcephaly, immunodeficiency, and a history of recurrent infections, as well as laboratory tests that assess chromosomal instability and the function of the NBN gene (source).
The Role of Genetic Testing in NBS
Genetic testing plays a crucial role in confirming the diagnosis of NBS. By analyzing the DNA of a suspected NBS patient, genetic testing can identify mutations in the NBN gene that are responsible for the disease. This information can help guide treatment decisions and provide valuable information for family planning.
In addition to confirming a diagnosis, genetic testing can also be used for carrier testing in families with a history of NBS. Identifying carriers of the mutated NBN gene can help couples make informed reproductive choices and better understand the risk of having a child with NBS.
Managing Nijmegen Breakage Syndrome
There is currently no cure for NBS, and management of the disease focuses on addressing the various symptoms and complications that arise. This may include treatment for recurrent infections, immunoglobulin replacement therapy for immunodeficiency, and regular monitoring for cancer development (source).
As our understanding of NBS continues to grow, it is hoped that new therapeutic approaches will be developed to address the underlying genetic defects and improve the quality of life for 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)