Changes in Phenotype of Bloom´s Syndrome with New Manifestations in Adult Individuals
Bloom´s syndrome results from autosomal recessive mutations in the BLM gene located on human chromosome 15 at 15q26.1, encoding a DNA helicase with homology to RecQ in E. coli (MIM 210900). Its phenotype includes (i) pre- and postnatal growth retardation, (ii) facial features with dolichocephaly and a narrow face, (iii) light-sensitive facial telangiectasia in most patients, (iv) manifestations of genomic instability as revealed by a 10-fold increase of spontaneous sister chromatid exchanges, breaks and homologous exchanges between chromosomes, and an increased rate of somatic mutations. Affected individuals develop similar types of cancer as in the population, but at a much younger age (about 1 in 4).
Eberhard Passarge and Heiko Löser
We report data of a longterm study of the natural history of 15 individuals with Bloom´s syndrome observed during the past 38 years in Germany. We found that the phenotype in adult individuals becomes less distinctive with age than it is in children. In spite of persistent feeding difficulties, such as lack of appetite or regurgitation, adult individuals tend to gain weight. A new finding is development of diabetes mellitus type 1 or type 2. This has been observed in 27 of 117 patients (23%) of individuals in the Bloom´s Syndrome Registry (J. German et al., unpublished data). The skin manifestations tend to improve with age. We diagnosed Bloom´s syndrome prenatally in a family known to be at risk. When the parents were informed about this diagnosis they changed their mind and decided to carry the pregnancy to term. Retarded growth was evident during all stage of the pregnancy and the affected infant weighed only 2000 g at birth at 40 weeks of gestation. However, he lacked the typical appearance of Bloom´s syndrome. We conclude that the phenotype of Bloom´s syndrome is wider than recorded previously. It remains to be seen whether the molecular type of mutation present in an individual influences the phenotype.
(Supported in part by the Deutsche Forschungsgemeinschaft, Bonn, Germany).