Nijmegen breakage syndrome, also known as Seemanova syndrome or Berlin breakage syndrome, is a rare autosomal recessive syndrome of chromosomal instability.
- microcephaly present at birth and
- progressive with age
- dysmorphic facial features
- mild growth retardation
- mild-to-moderate intellectual disability
- in females: hypergonadotropic hypogonadism
The cause is considered a founder mutation in the NBS1 gene (c.657_661del5) on chromosome 8q21. It is most common in West Slavic populations. The role of the NBS1 protein is to arrest the cell cycle in the S phase when there are errors in the cell DNA; and to interact with FANCD2 that can activate the BRCA1/BRCA2 pathway of DNA repair. As a result of a NBS1 defect, there is a higher frequency of malignancies 1.
Patients with NBS carry hypersensitivity to x-radiation and gamma radiation, therefore CT is a relative contraindication.
Only small descriptive series exist on the MRI features in NBS patient 2,3.
Features present in all patients were:
- decreased size of frontal lobes and narrow frontal horns of the lateral ventricles
- sinusitis as a result of primary immunodeficiency
Features present in some patients were:
- agenesis of the posterior part of the corpus callosum
- temporal horn dilatation
Features in a few patients were:
- callosal hypoplasia
Treatment and prognosis
There is no specific treatment for this syndrome. Hematopoietic stem cell transplantation can be considered. The prognosis is poor due to the high frequency of malignancies.
History and etymology
The condition was first described in the Dutch city of Nijmegen.
The alternative name for the condition, "Seemanova syndrome", is named after Eva Seemanova, a Czech geneticist, publication in 1985 4.
- 1. Chrzanowska KH, Gregorek H, Dembowska-Bagińska B et-al. Nijmegen breakage syndrome (NBS). Orphanet J Rare Dis. 2012;7 (1): 13. doi:10.1186/1750-1172-7-13 - Free text at pubmed - Pubmed citation
- 2. Bekiesińska-Figatowska M, Chrzanowska KH, Sikorska J et-al. Cranial MRI in the Nijmegen breakage syndrome. Neuroradiology. 2000;42 (1): 43-7. Pubmed citation
- 3. Bekiesińska-Figatowska M, Chrzanowska KH, Jurkiewicz E et-al. Magnetic resonance imaging of brain abnormalities in patients with the Nijmegen breakage syndrome. Acta Neurobiol Exp (Wars). 2005;64 (4): 503-9. Pubmed citation
- 4. Seemanová E, Passarge E, Beneskova D et-al. Familial microcephaly with normal intelligence, immunodeficiency, and risk for lymphoreticular malignancies: a new autosomal recessive disorder. Am. J. Med. Genet. 1985;20 (4): 639-48. doi:10.1002/ajmg.1320200410 - Pubmed citation
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