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Nijmegen Breakage Syndrome Follow-up

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

Further Outpatient Care

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.

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Further Inpatient Care

Further inpatient care is needed in some Nijmegen breakage syndrome (NBS) patients with severe recurrent infection. Inpatient care is needed in all patients diagnosed with malignancy.

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Deterrence/Prevention

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.

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Complications

Recurrent pneumonia and bronchitis may result in bronchiectasis or respiratory insufficiency.

Recurrent otitis media may result in draining ear(s) or mastoiditis.

Malignancies occur frequently in patients with Nijmegen breakage syndrome.

An adverse reaction to radiation therapy, chemotherapy, or both in patients with unrecognized Nijmegen breakage syndrome may result in toxic death.

At least 3 patients who had medulloblastoma and received radiation before being diagnosed with Nijmegen breakage syndrome were fatally injured, and they eventually died from complications of the therapy.[9, 53, 54]

Alopecia was an adverse effect observed in a Polish patient with acute myeloblastic leukemia given an 18-Gy dose of cranial irradiation for CNS prophylaxis. However, another Polish patient manifested no complications after receiving an identical dose by prophylactic cranial irradiation for high-risk group T-cell acute lymphoblastic leukemia. Both patients were treated for the malignancy before the diagnosis of Nijmegen breakage syndrome was established (Chrzanowska, unpublished data).

Physicians should be aware of the possibility that Nijmegen breakage syndrome is underdiagnosed in children with malignant diseases in geographical areas where the disease is less frequent.

A high index of suspicion is necessary for patients who (1) develop any type of malignancy and have congenital defects (eg, microcephaly) and (2) develop lymphoid malignancy at a very young age (younger than 3 y).

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Prognosis

Currently, the long-term prognosis for patients with Nijmegen breakage syndrome appears to be a bit more positive as a result of more effective prevention, control, and treatment of infections. Premature death occurs from aggressive malignancy; however, experience gained in diagnostics and management of lymphoid malignancies over the last few years has led to reduced mortality. Survival to more than the the third decade has been recorded.

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Patient Education

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. To find a genetics or prenatal diagnosis clinic, see GeneTests, Laboratory Directory.

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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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†



Czech



He*
c.657_661del5



(657del5)



6 Frameshift Truncated



protein (233 aa)



>90%



Slavic



founder mutation



Ho‡



(He)



c.681delT 6 Frameshift Truncated



protein (229 aa)



1



Russian



He
c.698_701del4



(698del4)



6 Frameshift Truncated



protein (236 aa)



2



English



Ho



He



c.742_743insGG



(742insGG)



7 Frameshift Truncated



protein (251 aa)



1



Italian



Ho
c.835_838del4



(835del4)



7 Frameshift Truncated



protein (279 aa)



1



Italian



Ho
c.842_843insT



(842insT)



7 Frameshift Truncated



protein (283 aa)



1



Mexican



Ho
c.900_924del25



(900del25)



8 Frameshift Truncated



protein (305 aa)



1



Moroccan



Ho
c.976C>T 8 Nonsense Q326X 1



Dutch



Ho
c.1089C>A 9 Nonsense Y363X 3



§



Pakistani



Ho
c.1142delC 10 Frameshift Truncated



protein (402 aa)



2



Canadian



He
*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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