What is Nijmegen breakage syndrome?

Nijmegen breakage syndrome is a rare hereditary syndromic disease associated with an increased risk of cancer. Its features include a characteristic facial expression caused by a small head and a receding chin, immunodeficiency, and an increased susceptibility to infections. The most commonly associated tumors are malignant lymphomas.

How is Nijmegen breakage syndrome diagnosed?

The diagnosis of Nijmegen breakage syndrome is suspected based on the typical appearance (see the clinical presentation) and confirmed through genetic tests.

What is the risk of cancer?

Clinical Presentation

Patients with Nijmegen breakage syndrome exhibit certain typical clinical features, including the following:

  • Small head

  • Dwarfism (short stature)

  • Sloping forehead, palpebral fissures that are inclined upwards, a prominent nose, relatively large ears, and a small or receding chin

  • Immunodeficiency, which can lead to recurring infections, particularly those affecting the airways

  • Malignant diseases (see below)

  • Timely achievement of developmental milestones in the first year of life, with mildly to moderately low intelligence after age 7.

  • Irregular skin pigmentation

The risk that a patient with Nijmegen breakage syndrome will develop a malignant disease is 40% before the age of 20. The following tumors are most commonly associated with Nijmegen breakage syndrome:

  • T-cell lymphomas (55%)

  • B-cell lymphomas (45%)

  • Brain tumors (medulloblastomas, gliomas)

  • Rhabdomyosarcomas

Heterozygous carriers of the mutation (meaning that only one allele is affected, e.g. parents) have an increased risk of developing breast and prostate cancer.

What causes Nijmegen breakage syndrome?

This gene defect causes a flaw in the DNA repair system. Errors that occur in the DNA can no longer be corrected as normal. In addition, the chromosomes – the carriers of the hereditary material – are more fragile than healthy chromosomes.

Is there a treatment?

The treatment mainly consists of diagnosing preliminary cancer stages as early as possible. Treating cancer in people with Nijmegen breakage syndrome requires special care and should only be done at centers with a lot of experience.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

Once Nijmegen breakage syndrome has been diagnosed, a thorough basic examination is recommended. It is important to regularly monitor the progression and to record and document body growth and the frequency of infections over time. Annual laboratory testing, annual skin screening, and a six-monthly dental examination should be striven for as well.

Specifically, the following examinations are recommended:

  • Hematology-oncology: annual blood count, including lactate hydrogenase (LDH), HPV vaccination

  • Dermatology: annual skin examination

  • Pulmonology: basic examination following the diagnosis, and during the progression if there are lung problems

  • Gastroenterology/nutrition: basic examination following the diagnosis, and during the progression if there are problems

  • Endocrinology: growth documentation (size, weight, head circumference), ovarian function testing for women

  • Neurology: developmental testing and early support as needed

  • Orthopedics: basic examination and as needed

  • Dental: six-monthly checkups

In addition, it is helpful to measure the immunoglobulin level.

Self-Care and Support

What should I pay special attention to?

  • Reduction/avoid exposure to radiation (e.g. X-rays, computer tomography, radiation therapy) if possible

  • Possibly vitamin E and folic acid supplements after consulting with the doctor

  • Administration of immunoglobulin if there is a strong tendency toward infection

  • Hormone replacement therapy if necessary

  • Breast self-examination for affected women

Support Groups and Additional Information