Familial chronic myeloproliferative disorders: clinical phenotype and evidence of disease anticipation.

PURPOSE: 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.

PATIENTS AND METHODS: 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.

RESULTS: 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).

CONCLUSION: 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.