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Nijmegen Breakage Syndrome
Tuesday, 30 March 2004
Tuesday, 30 March 2004
Berlin Breakage Syndrome, Seemanova Syndrome

What

Nijmegen breakage syndrome is a rare, inherited genetic disorder that is characterized by a small head, growth retardation, recurrent respiratory infections, premature ovarian failure in females, and an increased risk of developing childhood cancer (primarily lymphomas).

Who

The frequency of Nijmegen syndrome is estimated to be near 1 in every 100,000 live births. Individuals of Eastern European and Slavic descent are at a higher risk. Males and females are equally affected.

Signs and Symptoms

Children with Nijmegen breakage syndrome may exhibit all of the following:

  • Progressive growth retardation beginning with low birth weight
  • Small head size
  • Distinct facial features: sloping forehead, upslanting eyes, long nose, big ears, small jaw
  • Developmental delay and mild retardation in early childhood
  • Repeated episodes of pneumonia, bronchitis, and occasionally urinary infections.
  • Irregular pigmentation of the skin
  • Absence of menstrual periods in older females.

Possible Causes

The cause of Nijmegen breakage syndrome has been linked to mutations in a gene known as NBS1. NBS1 is responsible for producing a protein that repairs breaks in DNA within chromosomes. These breaks are part of the normal process of development in the immune system, and also occur naturally due to every day exposure to radiation. There is always some radiation that people are exposed to from the sun and natural sources. The accumulation of unrepaired DNA breaks leads to organ damage and predisposes individuals to cancers. Nijmegen breakage syndrome is inherited through an autosomal recessive manner, meaning two copies of the defective NBS1 gene are needed for a child to be affected.

Diagnosis

Making the diagnosis of Nijmegen breakage syndrome depends upon linking the characteristic facial features, growth delay, and history of repeated infections with special molecular genetic blood tests. Your doctor may order studies that can determine the maturity of the immune system. Small doses of radiation may be used on blood samples to identify cells that undergo DNA breakage easily. In females, elevated levels of an ovarian hormone named FSH can be diagnostic for premature ovary failure. An MRI (magnetic resonance imaging) of the brain may show structural abnormalities while CT (computerized tomography) is not allowed given the high amounts of radiation it bestows upon the patient.

Treatment

There is no cure for Nijmegen breakage syndrome. Medicines such as intravenous immunoglobulin (IVIG) and preventive antibiotics can help reduce the number of lung and sinus infections. In children with cancer, the treatment regimens must be changed to limit the doses of chemotherapy medications and radiation to accommodate the inability to repair DNA after radiation damage. Bone marrow transplantation may be a consideration if there is an appropriate sibling donor. Consultation with an endocrinologist is important for affected females as hormonal therapy to prevent osteoporosis can be started when the age is right.

Prognosis

Children with Nijmegen breakage syndrome usually do not survive beyond young adulthood, due to cancers and repeated infections.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

Gene Reviews
Good summary of disease facts and management geared for healthcare professional.

Nijmegen Breakage Syndrome Website
Italian based website with good information and resources for families.

Premature Ovarian Failure Support Group
Great website dedicated to supporting women with ovarian failure issues.

Medline Plus
Good general information for families who want to learn more about transplant.

Nijmegen Breakage Syndrome Mutation Database
Technical website run by Virginia Mason Research Center.

International Birth Defects Information Systems
International website dedicated to raising awareness and support for rare birth defects.

Google Search for Nijmegen Breakage Syndrome

References and Sources

Chrzanowska K: Emedicine article: http://www.emedicine.com/derm/topic725.html Muschke, P. et al. (2004) Retrospective diagnosis and subsequent prenatal diagnosis of Nijmegen breakage syndrome. Pren Diagn. 24: 111-113.