RT Book, Section
A1 Schneider, Susanne A.
A1 Bhatia, Kailash P.
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102705155
T1 Ataxia-Telangiectasia
T2 Clinical Genomics: Practical Applications in Adult Patient Care
YR 2014
FD 2014
PB McGraw-Hill Education
PP New York, NY
SN 9780071622448
LK accessmedicine.mhmedical.com/content.aspx?aid=1102705155
RD 2024/04/20
AB Disease  summary:Ataxia-telangiectasia  (AT)  is  a  recessive  hereditary  genomic  instability  disorder  occurring  in  between  1  out  of  40,000  and  1  out  of  100,000  persons  worldwide.AT  is  clinically  characterized  by  early-onset  progressive  cerebellar  ataxia,  telangiectasias  of  the  skin  and  bulbar  conjunctiva,  progressive  apraxia  of  eye  movements,  increased  susceptibility  to  sinopulmonary  infections,  endocrine  deficiencies  and  lymphoreticular  malignancies,  and  other  malignant  tumors.  Atypical  forms  including  adult-onset  AT  and  AT  with  early-onset  dystonia  including  levodopa-responsive  dystonia  may  occur.Laboratory  confirmation  of  the  diagnosis  is  based  on  a  combination  of  increased  serum  α-fetoprotein  level,  increased  in  vitro  radiosensitivity,  decreased  or  absent  intracellular  ATM  protein  levels  on  western  blotting,  and  mutations  in  the  ATM  gene.Hereditary  basis:AT  is  due  to  ATM  gene  mutations,  which  follow  an  autosomal  recessive  inheritance  pattern.  More  than  600  mutations  of  the  ATM  gene  have  already  been  identified,  most  of  which  are  unique  to  single  families  (private  mutations).  Genetic  screening  can  be  extensive  and  remains  unsuccessful  in  5%  to  15%  of  cases.Differential  diagnosis:AT  variants  have  been  recognized  which  include  the  Nijmegen  breakage  syndrome  due  to  mutations  in  the  NBS1  gene  on  chromosome  8q21,  and  AT-like  disorder  (ATLD)  due  to  mutations  in  the  MRE11.Ataxia  with  ocular  motor  apraxia  types  1  and  2  can  clinically  mimic  AT.  Other  ataxia  disorders  including  Friedreich  ataxia  and  vitamin  E-associated  ataxia  should  also  be  considered.