Summary An investigation of 22 new patients with Shwachman‐Diamond syndrome (SDS) and the follow‐up of 14 previously reported cases showed that (i) clonal chromosome changes of chromosomes 7 and 20 were present in the bone marrow (BM) of 16 out of 36 cases, but if non‐clonal changes were taken into account, the frequency of anomalies affecting these chromosomes was 20/36: a specific SDS karyotype instability was thus confirmed; (ii) the recurrent isochromosome i(7)(q10) did not include short arm material, whereas it retained two arrays of D7Z1 alphoid sequences; (iii) the deletion del(20)(q11) involved the minimal region of deletion typical of myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML); (iv) only one patient developed MDS, during the rapid expansion of a BM clone with a chromosome 7 carrying additional material on the short arms; (v) the acquisition of BM clonal chromosome anomalies was age‐related. We conclude that karyotype instability is part of the natural history of SDS through a specific mutator effect, linked to lacking SBDS protein, with consequent clonal anomalies of chromosomes 7 and 20 in BM, which may eventually promote MDS/AML with the patients’ ageing.

Article abstract-Objective: An epidemiologic survey was conducted to determine the prevalence and incidence of MS in the city of Catania, Sicily, Italy. Prevalence rate was calculated as point prevalence at January 1,1995, and incidence during 1974 to 1995. Methods: The authors studied the frequency of MS in the community of Catania in a population of 333,075 inhabitants according to the 1991 census. The primary sources for the case ascertainment were the neurologic and motor rehabilitation departments, the MS Center, the Italian MS Association, private neurologists, and family doctors. All patients who satisfied the Poser criteria for clinically definite MS, laboratory-supported definite MS, clinically probable MS, and laboratory-supported probable MS were considered prevalent and incident cases. Results: One hundred ninetyfive patients with MS who had had the onset of disease on prevalence day in a population of 333,075 inhabitants were detected. The prevalence rate was 58.5 per 100,000 (95% CI 50.7 to 67.5). Prevalence was higher in women (62.0/100,000) than in men (54.8/100,000). The age-specific prevalence showed a peak in the group aged 35 to 44 (145

acquired TTP but with an atypical presentation. A suboptimal response to PEX, defined as the absence of a steadily declining lactate dehydrogenase level and an increase in the platelet count after 4-5 days of daily PEX in the context of ADAMTS13 >10%, would lead us to consider therapy with eculizumab over intensified PEX or immune-based therapy as might be considered in TTP.

BackgroundAn interstitial deletion of the long arms of chromosome 20, del(20)(q), is frequent in the bone marrow (BM) of patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and myeloproliferative neoplasms (MPN), and it is recurrent in the BM of patients with Shwachman-Diamond syndrome (SDS), who have a 30-40% risk of developing MDS and AML.ResultsWe report the results obtained by microarray-based comparative genomic hybridization (a-CGH) in six patients with SDS, and we compare the loss of chromosome 20 material with one patient with MDS, and with data on 92 informative patients with MDS/AML/MPN and del(20)(q) collected from the literature.ConclusionsThe chromosome material lost in MDS/AML/MPN is highly variable with no identifiable common deleted regions, whereas in SDS the loss is more uniform: in 3/6 patients it was almost identical, and the breakpoints that we defined are probably common to most patients from the literature. In some SDS patients less material may be lost, due to different distal breakpoints, but the proximal breakpoint is in the same region, always leading to the loss of the EIF6 gene, an event which was related to a lower risk of MDS/AML in comparison with other patients.

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