Rumi Elisa, Passamonti Francesco, Della Porta Matteo G, Elena Chiara, Arcaini Luca, Vanelli Laura, Del Curto Cecilia, Pietra Daniela, Boveri Emanuela, Pascutto Cristiana, Cazzola Mario, Lazzarino Mario
Department of Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Viale Golgi 49, 27100 Pavia, Italy.
J Clin Oncol. 2007 Dec 10;25(35):5630-5. doi: 10.1200/JCO.2007.12.6896. Epub 2007 Nov 12.
Chronic myeloproliferative disorders (CMDs) have sporadic occurrence. However, familial clustering is reported. The purpose of this study was to assess the prevalence and the clinical phenotype of familial CMDs, and to study the anticipation of disease onset in successive generations.
Among 458 patients with apparently sporadic CMDs, an interview-based investigation of family history was performed to identify familial cases. The clinical phenotype of familial CMDs was compared with that of sporadic CMDs. Anticipation was studied evaluating age at diagnosis and telomere length in successive generations.
Among 458 patients with apparently sporadic CMDs, the prevalence of familial cases was 7.6% (35 pedigrees; 75 patients). Kolmogorov-Smirnov and two-tailed Fisher's exact tests did not demonstrate significant differences in clinical presentation between patients with familial and sporadic CMDs. Within 544 person-years of follow-up, patients with familial CMDs developed similar complications and disease evolutions as those with sporadic CMDs. The comparison of second-generation and first-generation patients showed a significantly younger age at diagnosis (Wilcoxon matched-pair test, P = .001) and a significantly higher age-dependent hazard of CMD onset (Nelson-Aalen method, P < .001) in patients of the second generation. A significant shortening of telomere length was highlighted in offspring compared with parent (P = .043).
This study indicates that a thorough investigation of family history should be part of the initial work-up of patients with CMDs. Patients with familial CMDs show the same clinical features and suffer the same complications as patients with sporadic disease. Age distribution between parent and offspring and telomere length shortening provide evidence of disease anticipation.
慢性骨髓增殖性疾病（CMDs）呈散发性发生。然而，也有家族聚集性的报道。本研究的目的是评估家族性CMDs的患病率和临床表型，并研究连续几代人中疾病发病的遗传早现现象。
在458例明显为散发性CMDs患者中，通过基于访谈的家族史调查来确定家族性病例。将家族性CMDs的临床表型与散发性CMDs的进行比较。通过评估连续几代人的诊断年龄和端粒长度来研究遗传早现现象。
在458例明显为散发性CMDs患者中，家族性病例的患病率为7.6%（35个家系；75例患者）。Kolmogorov-Smirnov检验和双尾Fisher精确检验未显示家族性和散发性CMDs患者在临床表现上有显著差异。在544人年的随访期内，家族性CMDs患者发生的并发症和疾病进展与散发性CMDs患者相似。第二代和第一代患者的比较显示，第二代患者的诊断年龄显著更小（Wilcoxon配对检验，P = .001），且CMD发病的年龄依赖性风险显著更高（Nelson-Aalen方法，P < .001）。与父母相比，后代的端粒长度显著缩短（P = .043）。
本研究表明，对CMDs患者进行初步检查时应全面调查家族史。家族性CMDs患者与散发性疾病患者具有相同的临床特征和相同的并发症。父母与后代之间的年龄分布以及端粒长度缩短为疾病遗传早现提供了证据。
