Chromosomal Instability Syndromes

Fanconi Anemia

Ataxia-Telangiectasia

Bloom

Nijmegen Breakage Syndrome

ICF syndrome

Roberts

Variegated Aneuploidy with Premature Centromere Separation

Dominantly inherited premature centromere division

Werner

Xeroderma pigmentosum

Cockayne

Trichothiodystrophy

Rothmund Thomson

Epidemiology and Etiology:

· Defects in proteins involved in:

· Replication

· Repair

· Recombination

· Generation of novel immunoglobulin genes

· Sister chromatin exchange

· Cell cycling

· Chromosomal division

· Autosomal recessive mostly

· Secondary to other systemic diseases:

· Scleroderma

· SLE

Common sites:

·

Gross features:

·

Histologic features:

·

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

· Elevated spontaneous aberration frequency

· Elevated level of SCE

· Hypersensitivity to chromosome-damaging agents

· Clonal or recurrent stable chromosome rearrangements

Other features:

· Tumour predisposition

· Immune deficiency

· Growth retardation

· Premature aging

References:

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