Nijmegen breakage syndrome

Nijmegen breakage syndrome, also known as Seemanova syndrome or Berlin breakage syndrome, is a rare autosomal recessive syndrome of chromosomal instability.

Clinical presentation

• microcephaly present at birth and
• progressive with age
• dysmorphic facial features
• mild growth retardation
• mild-to-moderate intellectual disability
• in females: hypergonadotropic hypogonadism

Pathology

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 .

Radiographic features

CT 

Patients with NBS carry hypersensitivity to x-radiation and gamma radiation, therefore CT is a relative contraindication.

MRI

Only small descriptive series exist on the MRI features in NBS patient .

Features present in all patients were:

• microcephaly
• 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
• colpocephaly
• 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 .