Table II.

Chromosome Breakage Syndromes Inherited as Recessive Disorders and Associated with Cancer Predisposition

Syndrome	Clinical Appearance	Chromosome Effects	Gene
Ataxia-Telangiectasia	Progressive cerebellar ataxia; oculo-cutaneous telangiectases, immune deficiency; predisposition to cancers, especially leukemias and lymphomas; elevated cancer incidence in heterozygotes	Chromatid breaks; formation of dicentric and acentric chromosomes, radiosensitivity	ATM
Xeroderma Pigmentosum	Sensitivity to sunlight, leading to “parchment skin” with pigmentary disturbances, multiple skin cancers (basal cell and squamous cell carcinoma, melanoma), leukemias, sarcomas; mental deterioration, ocular abnormalities	Defective nucleotide excision repair, elevated number of crossovers between sister chromatids	XPA-XPG, XPV
Bloom Syndrome	Short stature, disfiguring facial rashes made worse by sunlight; immunological problems; predisposition to leukemias and lymphomas, Wilms tumor, medulloblastoma and other solid tumors	Chromosome breaks; elevated number of crossovers between sister chromatids	BLM
Fanconi Anemia	Anemia and pancytopenia; short stature; radial aplasia and other skeletal defects; hyper- or hypopigmentation and cafe-au-lait spots; renal and genitourinary malformations; cardiac, gastrointestinal, and central nervous system abnormalities, predisposition to cancer, especially leukemia but also solid tumors	Chromatid breaks, gaps; exchange of segments between chromosomes; hypersensitivity to cross-linking agents	FANCA, FANCB, FANCC, BRCA2 a (FANCD1)b, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL
AT-like disorder	Ataxia, immune deficiency, neurological problems, predisposition	Chromosome breaks, radiosensitivity	MRE11A
Nijmegen Breakage Syndrome	Microcephaly, distinct facial appearance, short stature, immunodeficiency, radiation sensitivity, predisposition to lymphoma, glioma, medulloblastoma, rhabdomyosarcoma	Chromosome breaks	NBS1
Mosaic Variegated Aneuploidy	Microcephaly, short stature, eye abnormalities, CNS abnormalities, seizures, intellectual disability, predisposition to Wilms tumor, nephroblastoma, rhabdomyosarcoma, leukemia	Anueploidy	BUB1B
Werner Syndrome	Premature aging, short stature, cancer predisposition (especially sarcomas)	Chromosomal deletions and translocations	WRN
Rothmund-Thomson Syndrome	Skin atrophy, telangiectasia, hyper- and hypopigmentation, skeletal abnormalities, elevated risk of cancer (especially osteosarcomas and skin cancer)	Chromosomal instability	RECQL4
LIG4 Syndrome	Unusual facies, microcephaly, developmental delay, pancytopenia, immune deficiency, predisposition to leukemia	Defects in DNA strand break repair, radiosensitivity,	LIG4
46BR Syndrome	Immune deficiency, sun sensitivity, stunt growth, predisposition to lymphoma	Chromosomal instability	LIG1
MUTYH-Associated Polyposis	Colonic adenomas and cancer, duodenal and gastric adenomas and cancer, elevated risk of ovarian, bladder, breast, endometrial and thyroid cancer	Defects in excision repair of adenine opposite 8-oxoguanine, resulting in elevated C:G to A:T transversions	MUTYH

^aBiallelic mutations in BRCA2 cause Fanconi Anemia (recessive), whereas monoallelic mutations are associated with BRCA2 breast/ovarian cancer syndrome (dominant).

^bAlternative gene name