Disease
Description
Cited
literature
This
website deals with clinical management, diagnosis, therapeutic options of the
disease and genetic counselling in general terms. The information in this
website can by no means substitute for medical advice to the individual patient
or family.
The Nijmegen Breakage Syndrome (NBS) was
first delineated by C. Weemaes and colleagues (Nijmegen, The
Netherlands) in 1981.
They observed a Dutch family with consanguineous parents and two boys affected with
microcephaly, growth defect, skin abnormalities, mental retardation and
immunodeficiency; a high incidence of chromosome 7 and 14 rearrangements was
demonstrated in the cultured lymphocytes of the
younger brother. Since then around 200 cases have been identified
worldwide and an International
NBS Registry is currently held in Nijmegen. The NBS1 gene (whose biallelic
mutations cause NBS) was identified in 1998.
NBS is considered as a rare autosomal recessive disease, but its actual
prevalence is not known. The disease appears to be more frequent among Eastern and
Central European populations and NBS patients of Slavic origin share a conserved
haplotype with a unique mutation 657del5 (more than 90% of all NBS patients are
homozygous for this mutation). The carrier rate of the 657del5 allele has been
studied in three Slav populations (Czech Republic, Poland, Ukraine) and
assessed at 1/177.
NBS has also been reported in the United States, France,
United Kingdom, Spain, Turkey, Morocco, Argentina, Chile and New Zealand.
In Italy, four NBS patients have been described. One of them is from
North-Eastern Italy and is homozygous for the 657del5 mutation. In two other Italian patients two different private mutations (742ins2 and
835del4) were found. A girl born in Italy, but of Moroccan origin, was
demonstrated to be homozygous for a further mutation (900del25).
The Italian patient who is homozygous for the 742ins2 mutation is now 53 year
old.
Clinical phenotype
Cytogenetics and cellular phenotype
Page last updated on: 18th May 2007