Nijmegen Breakage Syndrome Treatment & Management

Updated: Sep 16, 2022
  • Author: Krystyna H Chrzanowska, MD, PhD; Chief Editor: William D James, MD  more...
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Medical Care

No specific therapy is available for Nijmegen breakage syndrome (NBS).

Substitution with immunoglobulins (ie, intravenous immunoglobulin [IVIG] therapy) is indicated in patients with agammaglobulinemia (serum concentration of IgG < 2.5-3 g/L, depending on patient age) and in children with IgG2 deficiency (< 0.48 g/L in patients aged 2-5 y and < 0.72 g/L in patients >5 y). Before IVIG is started, the presence of anti-IgA antibodies must be determined in patients with IgA deficiency. In such cases, the subcutaneous administration of immunoglobulins is advocated to prevent shock, which can occur in patients with anti-IgA antibodies. A pediatric immunologist must make the decision to start substitution therapy.

Consider antibiotic prophylaxis in patients with recurrent respiratory tract infections. Urinary tract infections due to congenital malformations of the kidneys occur in some children; antibiotic prophylaxis is indicated in these patients.

Cancer treatment must be modified in Nijmegen breakage syndrome patients with malignancy because conventional doses of radiotherapy and chemotherapy may lead to severe (even lethal/ life-threatening) toxic complications. [88] Curative therapy, however, is possible and should be attempted. The intensity of therapy must be adapted to individual risk factors and tolerance. The use of radiomimetics, alkylating agents, and epipodophyllotoxins should be avoided, and the dose of methotrexate should be limited. [89, 90, 91, 92] Anthracycline-induced cardiomyopathy was reported in one patient, and, therefore, echocardiographic monitoring is strongly recommended. [93]

Bone marrow transplantation (BMT) or hematopoietic stem cells transplantation (HSCT) is an option that can be considered in some patients with Nijmegen breakage syndrome. [94] HSCT experience in six Nijmegen breakage syndrome patients in Europe was reported, of whom two, initially diagnosed as atypical Fanconi anemia, were transplanted in order to correct severe immunodeficiency, [48] and the reminding four underwent HSCT for refractory, recurring, or secondary malignancy. [95] In five patients, a reduced-intensity conditioning regimen was implemented. In 2015, Wolska-Kuśnierz et al analyzed data on14 transplanted Nijmegen breakage syndrome patients to date and nine of them survived from 1.4-11 years. [6] Shortly after, Woźniak et al presented successful nonmyeloablative umbilical cord blood transplantation in a 19-month-old child with Nijmegen breakage syndrome presenting with severe combined immune deficiency (SCID). [96] Further follow-up is needed to monitor long-term effects, including the development of malignancies.

Prepubertal female patients with delayed or absent sexual maturation require the systematic care of a (pediatric) endocrinologist, gynecologist, or both. When hypergonadotropic hypogonadism is confirmed (serum FSH level >40 IU/L, low E2 level), substitution hormone therapy to support the development of secondary sex characteristics and to prevent osteoporosis must be considered when the patient reaches the appropriate age.

Vitamin E supplementation in doses appropriate for age and body weight is recommended, as in individuals with other chromosome instability disorders.



Consultations with the following various specialists may be required:

  • Pediatric immunologist

  • Oncologist

  • Pulmonologist

  • Neurologist

  • Endocrinologist

  • Gynecologist

  • Others, as determined by history and physical examination findings

Offer genetic counseling to provide families with information about the high recurrence risk and the possibility of prenatal diagnosis. Nijmegen breakage syndrome is inherited in an autosomal recessive manner. Parents of an affected child are obligate carriers of a single copy of a disease-causing mutation in the NBS1 gene and have a 25% likelihood (1:4) of giving birth to an affected child. Heterozygotes are asymptomatic. However, some reports have suggested an increased risk of malignancy in carriers of the common Slavic mutation, 657del5. [97, 98] Therefore, monitoring parents for malignancy is recommended.

Delayed speech development is observed in many children, and speech therapy is needed to correct articulation problems.

Most patients with mental retardation require educational support. They may need to attend special education classes or schools.



Infants and young children with Nijmegen breakage syndrome demonstrate striking psychomotor hyperactivity and have a short attention span. Generally, all children with Nijmegen breakage syndrome have a gentle personality and, despite being shy, they are usually capable of good social interactions.



Prenatal diagnosis is possible for families with a 25% risk of having an affected child. Molecular genetic analysis is the method of choice. However, the identification of disease-causing mutations in both alleles of the NBS1 gene is necessary before prenatal testing can be performed.

Fetal DNA is obtained either by chorionic villous sampling at 10-12 weeks' gestation or by early amniocentesis at 13-15 weeks' gestation.


Long-Term Monitoring

Further outpatient care (eg, IVIG therapy, infection treatment) is determined by the degree of immune deficiency and clinical course.

Periodic follow-up is indicated to monitor immune status, physical growth, and intellectual development.

Systematic periodic monitoring for malignancy development is mandatory.