Table 1 Disorders with chromosomal instability to be considered in the differential diagnosis of NBS
Condition | MIM | Gene | Clinical features | In vitro sensitivity to damaging agents |
|---|---|---|---|---|
NBS | 251260 | NBN (NBS1) | Microcephaly, dysmorhic face, growth retardation (OFC more retarded than height); reduced fertility (hypergonadotropic hypogonadism in females); combined cellular and humoral immunodeficiency | IR, Bleomycin; Alkylating agents (MMC, DEB)--mild |
NBSLD | 604040 | RAD50 | Microcephaly, dysmorphic face, growth retardation (OFC more retarded than height); mild spasticity, non-progressive ataxia; normal puberty; no immunodeficiency | IR, Bleomycin |
A-T | 208900 | ATM | Progressive cerebellar ataxia, oculomotor apraxia, bulbar and skin telangiectasia; (microcephaly only in exceptional cases); combined cellular and humoral immunodeficiency | IR, Bleomycin; alkylating agents (MMC, DEB) -mild |
ATLD | 604391 | MRE11 | Microcephaly (in some); cerebellar ataxia (late onset/slow progressive); oculomotor apraxia; no telangiectasia; no immunodeficiency | IR |
DNA LIG4 syndrome | 606593 | DNA LIG4 | Microcephaly, dysmorhic face, growth retardation (OFC more retarded than height); combined cellular and humoral immunodeficiency | IR, Bleomycin |
NHEJ1 | 611291 | NHEJ1 | Microcephaly, dysmorhic facies, severe growth retardation; severe combined cellular and humoral immunodeficiency | IR (variable) |
FA | 227650 | FANC* | Microcephaly (in some), growth retardation, skeletal abnormalities (radial defect); reduced fertility (hypergonadotropic hypogonadism in males); pancytopenia (progressive); no immunodeficiency | Alkylating agents (MMC, DEB); IR (mild) |
Seckel syndrome 1 (ATR-SS) | 210600 | ATR | Severe microcephaly, severe prenatal and postnatal growth retardation; developmental delay, mental retardation; pancytopenia; no immunodeficiency | Alkylating agents (MMC); UV (moderate) |
BS | 210900 | BLM (RECQL3) | Microcephaly, severe growth retardation (OFC retarded proportionally to height); no specific immunodeficiency | UV |
WBS | 613398 | DDX11 | Microcephaly, prenatal and postnatal growth retardation, deafness; developmental delay; no immunodeficiency | Alkylating agents (MMC) |