Dear Editor,

The recent article on the ocular manifestations of Bloom syndrome by Bhisitkul and Rizen [1] suggested that macular drusen may be an integral part of Bloom syndrome. Recently we published the finding of drusen in a young girl with Bloom syndrome [2]; we suspected that drusen might be expected in one of the premature aging syndromes, but at that time found little information on drusen as an ocular abnormality in Bloom syndrome.[3] Were drusen a characteristic ocular finding in Bloom syndrome? Did every Bloom syndrome patient have drusen? If not, then did Bloom syndrome have different mutations, some leading to drusen and others not, and was it necessary to pay greater heed to the Bloom syndrome patients with drusen because of increased risks?

More recently, we had the opportunity to study a family of two siblings with Bloom syndrome. The diagnosis of the siblings was made based on characteristic clinical and laboratory findings and elevated sister chromatid exchange (SCE) formation. Mutation analysis was not done. Both siblings with Bloom syndrome also had drusen. A third unaffected sibling didn't have drusen, nor did the parents. The clinical phenotypes of the two affected siblings were completely discordant. The first patient had severe clinical symptoms (chronic lung disease due to pulmonary fibrosis and bronchiectasis) as a clinical presentation of rapid progress and poor prognosis. The second patient was without symptoms. Therefore, drusen may be a characteristic ocular abnormality of Bloom syndrome, and can be present in Bloom syndrome patients with different clinical phenotypes. We have yet to understand the prognostic value of drusen, if any, for the clinical course of the disease. It is possible that different mutations might cause drusen and the clinical phenotype is dependent on the type of mutation. To the best of our current knowledge, genetic heterogeneity might be involved in Bloom syndrome.[4,5] The patient described by Bhisitkul and Rizen had drusen and developed leukemia during the 1 year follow-up period.[1] This gives some support to our opinion that "the probability of developing cancer in Bloom syndrome patients with drusen might be relatively higher than those without drusen". We do not disregard the cancer predisposition potential of the syndrome itself, but it is fair to say that our opinion expressed above has merit, and it would be prudent to pay greater heed to the Bloom syndrome patients with drusen.

In the light of our experiences and the article published in your journal, drusen appear to be a typical feature of Bloom syndrome. However, the significance of this finding remains undetermined.

Deniz Aslan, Sengul Ozdek, Sibel Ozdogan

References

1) Bhisitkul RB, Rizen M. Bloom syndrome: multiple retinopathies in a chromosome breakage disorder. Br J Ophthalmol. 2004;88:354-357.

2) Aslan D, Ozturk G, Kaya Z, Bideci A, Ozdogan S, Ozdek S, Gursel T. Early-onset drusen in a girl with bloom syndrome: probable clinical importance of an ocular manifestation. J Pediatr Hematol Oncol. 2004;26:256-257.

3) Dollfus H, Porto F, Caussade P, Speeg-Schatz C, Sahel J, Grosshans E, Flament J, Sarasin A. Ocular Manifestations in the Inherited DNA Repair Disorders. Surv Ophtalmol. 2003;48:107-122.

4) German J, Ellis NA, Proytcheva M. Bloom's syndrome. XIX. Cytogenetic and population evidence for genetic heterogeneity. Clin Genet. 1996;49:223-231.

5) Ellis NA, Lennon DJ, Proytcheva M, Alhadeff B, Henderson EE, German J. Somatic intragenic recombination within the mutated locus BLM can correct the high sister-chromatid exchange phenotype of Bloom syndrome cells. Am J Hum Genet. 1995;57:1019-1027.