Nijmegen Breakage Syndrome

Epidemiology and Etiology:

· NBS1 gene mutation

· Autosomal recessive

· May be involved in response to DNA double-strand breaks

· May be involved in meiotic recombination

Common sites:

·

Gross features:

· Small size

· Microcephaly

· Café au lait spots

Histologic features:

·

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

· NBS1 gene mutation (8q21)

· Founder mutation in all cases so far (2001)

· Cytogenetic workup:

· 50 G-banded mets for:

· chromosome 7 and 14 rearrangements

· chromosome breaks and rearrangements

· run a control sample

· 5 G-banded mets for constitutional karyotype

· Spontaneous cytogenetic abnormalities

· High level of chromosome rearrangements involving chr 7 and 14 (same as A-T but higher frequency)

· Inv(7)(p13q35)

· T(7;7)(p13;q35)

· T(7;14)(p13;q11)

· Low spontaneous chromosome breakage (same as A-T)

· Normal SCE frequency

· Induced cytogenetic abnormalities

· Increased sensitivity to X-rays and bleomycin

· X-irradiation studies can be used for diagnosis

Other features:

· Mental retardation

· Immunodeficiency

· Lymphoid malignancies

References:

· Rooney D. Human Cytogenetics: Malignancy and Acquired Abnormalities: A Practical Approach. 3rd ed. Oxford University Press; 2001.