Nijmegen breakage syndrome

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What is Nijmegen Breakage Syndrome?

Nijmegen Breakage Syndrome (NBS) is an inherited condition that increases the risk of cancer and reduces immune response. NBS is caused by harmful genetic changes, or mutations, in the NBN gene.

Infants with NBS are often born with small head size (microcephaly). Their physical growth is often slow, leaving them smaller than average for their age. They have characteristic features, including a sloping forehead, small chin, big ears, and a prominent nose, which become more apparent later in childhood. Many affected individuals have skeletal abnormalities of the fingers and toes.

Up to 40% of individuals with NBS will develop some sort of cancer by the age of 20. This is typically cancer of the immune system (lymphoma), but other types of cancer have been described. Individuals with NBS cannot tolerate the high doses of ionizing radiation often used to treat cancer and must find alternate treatment methods such as chemotherapy.

Individuals with NBS have a poor immune system and experience frequent infections in the lungs, ears, sinuses, and urinary tract. Recurrent pneumonia or bronchitis in those affected by NBS can be life-threatening. A patient's intellect appears to develop normally or nearly normally in early childhood but typically declines until the patient reaches mild-to-moderate levels of intellectual disability around the age of 10.

Additional considerations for carriers

Carriers of NBS do not show symptoms of the disease. However, studies have shown that some carriers, particularly of the common c.657_661del mutation, may have a greater-than-average risk of developing some types of cancer. These include breast cancer and prostate cancer. The exact risks for cancer depend on personal and family history. Carriers of NBS should consider genetic counseling to determine the most appropriate screening recommendations.

How common is Nijmegen Breakage Syndrome?

The prevalence of NBS is estimated to be 1 in 100,000 births, but there is currently insufficient population-specific prevalence information. The disease is most common in individuals of Eastern European or Slavic background, specifically those from Poland, the Czech Republic, and Ukraine.

How is Nijmegen Breakage Syndrome treated?

There is no treatment to address the underlying cause of NBS, but specific symptoms can be treated. Supplements such as vitamin E and folic acid may be helpful, and in some individuals, intravenous infusions with immunoglobulin or preventative antibiotics can be used to reduce infections. Special education and speech therapy may also address delays in development. Hormone replacement therapy may be useful for female sexual development, but most women with NBS are not fertile. Stem-cell transplantation may also be considered for treatment of NBS.

Large doses of radiation must be avoided in individuals with NBS, even before birth. Individuals with NBS should be monitored for proper growth and development, delayed onset of puberty, and early cancer signs.

What is the prognosis for an individual with Nijmegen Breakage Syndrome?

Some individuals with NBS do live into adulthood, though the lifespan does not typically extend beyond one's thirties or forties. Cancer is the most common cause of death among individuals with NBS, followed by lung infections leading to respiratory failure.