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Nijmegen Breakage Syndrome Treatment & Management

  • Author: Krystyna H Chrzanowska, MD, PhD; Chief Editor: William D James, MD  more...
Updated: Sep 29, 2014

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. 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.[73, 74, 75, 76] Anthracycline-induced cardiomyopathy was reported in one patient, and, therefore, echocardiographic monitoring is strongly recommended.[77]

Bone marrow transplantation (BMT) or hematopoietic stem cells transplantation (HSCT) is an option that can be considered in some patients with Nijmegen breakage syndrome. 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,[68] and the reminding four underwent HSCT for refractory, recurring, or secondary malignancy.[78] In five patients, a reduced-intensity conditioning regimen was implemented. One patient died from sepsis shortly after transplantation, but the reminding five were alive and followed for 1.7-8.1 years. 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.


Surgical Care

Neurosurgical treatment with a ventriculoperitoneal shunt may be necessary for patients with hydrocephaly. Surgical repair may also be required in cases of inherited malformations (eg, anal atresia, polydactyly).



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.[79, 80] 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.

Contributor Information and Disclosures

Krystyna H Chrzanowska, MD, PhD Head of Genetic Counseling Unit, Professor, Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland

Disclosure: Nothing to disclose.


Camila K Janniger, MD Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, Rutgers New Jersey Medical School

Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Abbvie<br/>Received income in an amount equal to or greater than $250 from: Optigenex<br/>Received salary from Optigenex for employment.

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A 6-month-old infant with Nijmegen breakage syndrome. Note microcephaly, the slightly upward-slanting palpebral fissures, and small chin.
Lateral facial features with sloping forehead and receding mandible are shown in a 6-month-old infant.
Typical facial features in a 9-year-old girl with Nijmegen breakage syndrome. Note the markedly upward-slanting palpebral features.
Lateral profile. This view shows a relatively long nose and receding mandible.
Cutaneous sarcoidosis in a patient with Nijmegen breakage syndrome. Note syndactyly of the second and third toes.
Vitiligo spots in a patient with Nijmegen breakage syndrome.
Progressive vitiligo in a patient with Nijmegen breakage syndrome.
Café au lait–like spots in a patient with Nijmegen breakage syndrome.
Preaxial polydactyly of the hand in a patient with Nijmegen breakage syndrome.
MRI in a patient with Nijmegen breakage syndrome shows large cerebrospinal fluid space that communicates with the left lateral ventricle and underdevelopment of the parietal lobes. Reprinted with permission from the Journal of Medical Genetics. Copyright 2001, BMJ Publishing Group.
MRI in a patient with Nijmegen breakage syndrome. Note compression of the posterior fossa and the lack of cerebellar atrophy. Reprinted with permission from the Journal of Medical Genetics. Copyright 2001, BMJ Publishing Group.
MRI in a patient with Nijmegen breakage syndrome. Note the small frontal lobes and the narrow frontal horns of the lateral ventricles. Reprinted with permission from the Journal of Medical Genetics. Copyright 2001, BMJ Publishing Group.
MRI in a patient with Nijmegen breakage syndrome. Note the partial defect of the corpus callosum. Reprinted with permission from the Journal of Medical Genetics. Copyright 2001, BMJ Publishing Group.
Table. NBS1 Gene Pathogenic Molecular Variants
Mutation Exon Mutation Type Change in Protein Number of Families and Origin Allelic Status
c.643C>T 6 Missense R215W 1†




6 Frameshift Truncated

protein (233 aa)



founder mutation



c.681delT 6 Frameshift Truncated

protein (229 aa)





6 Frameshift Truncated

protein (236 aa)







7 Frameshift Truncated

protein (251 aa)





7 Frameshift Truncated

protein (279 aa)





7 Frameshift Truncated

protein (283 aa)





8 Frameshift Truncated

protein (305 aa)



c.976C>T 8 Nonsense Q326X 1


c.1089C>A 9 Nonsense Y363X 3



c.1142delC 10 Frameshift Truncated

protein (402 aa)



*He - Heterozygous (compound with 657del5).

†Monozygotic twin-brothers (compound heterozygotes) with severe disease phenotype.[71]

‡Ho - Homozygous.

§Three nuclear families in 1 large family; proband diagnosed first as having Fanconi anemia (FA).[67, 68]

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