Expert Reviewed By: Dr. Brandon Colby MD
Severe combined immunodeficiency with sensitivity to ionizing radiation due to NHEJ1 deficiency, also known as Nijmegen breakage syndrome (NBS), is a rare autosomal recessive disorder that affects multiple aspects of an individual's health. In this article, we explore the clinical manifestations, genetic aspects, and laboratory findings related to NBS. We will also delve into the uses of genetic testing in understanding, diagnosing, and managing this complex disorder.
Clinical Manifestations of Nijmegen Breakage Syndrome
Individuals with NBS typically exhibit a range of symptoms, including:
- Microcephaly (a smaller than normal head size)
- Immunodeficiency, which can lead to recurrent infections
- Predisposition to malignancies, particularly lymphomas and leukemias
These clinical manifestations can vary in severity and may not be present in all individuals with NBS. It is important for healthcare providers to recognize these signs and symptoms and consider NBS as a potential diagnosis.
Genetic Aspects of Nijmegen Breakage Syndrome
NBS is caused by mutations in the NHEJ1 gene, which plays a crucial role in repairing DNA double-strand breaks. This gene is essential for maintaining the stability of an individual's genetic material. When the NHEJ1 gene is mutated, the body's ability to repair DNA damage is compromised, leading to the various clinical manifestations of NBS.
This disorder is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop NBS. Parents who are carriers of the NHEJ1 mutation have a 25% chance of having a child with NBS.
Laboratory Findings in Nijmegen Breakage Syndrome
Several laboratory tests can aid in the diagnosis of NBS, including:
- Chromosomal analysis, which may reveal characteristic chromosomal rearrangements
- Immunological testing, which can identify deficiencies in the immune system
- Radiosensitivity testing, which can assess the cells' ability to repair DNA damage caused by ionizing radiation
These tests can provide valuable information to healthcare providers, helping them to confirm a diagnosis of NBS and guide appropriate management strategies.
Genetic Testing for Nijmegen Breakage Syndrome
Genetic testing can play a vital role in the diagnosis and management of NBS. It can be particularly helpful in the following situations:
Confirming a Diagnosis
Genetic testing can be used to confirm a suspected diagnosis of NBS by identifying mutations in the NHEJ1 gene. This can be particularly helpful in cases where clinical manifestations are subtle or atypical.
Carrier Testing
Individuals with a family history of NBS or those from populations with a higher prevalence of NHEJ1 mutations may choose to undergo carrier testing. This can provide valuable information about an individual's risk of having a child with NBS and inform reproductive decision-making.
Prenatal Testing
When both parents are known carriers of NHEJ1 mutations, prenatal testing can be performed to determine if the fetus is affected by NBS. This information can help families and healthcare providers prepare for the potential medical needs of the affected child.
Preimplantation Genetic Diagnosis
Couples who are known carriers of NHEJ1 mutations and undergoing in vitro fertilization (IVF) may opt for preimplantation genetic diagnosis (PGD). PGD involves testing embryos for the presence of NHEJ1 mutations before implantation, allowing couples to select embryos that are not affected by NBS.
In conclusion, Nijmegen breakage syndrome is a rare and complex disorder with significant implications for affected individuals and their families. Genetic testing can provide critical information for diagnosing, managing, and preventing this disorder, helping to improve the quality of life for those affected by NBS.
For more information about Nijmegen breakage syndrome and its associated genetic testing, please refer to the following research article.
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)