Paris-Trousseau syndrome (PTS) is a rare inherited platelet-based bleeding disorder characterized by clinical features such as intellectual deficit, cardiac malformations, and facial abnormalities associated with thrombocytopenia and dysmegakaryopoiesis. Two morphologically distinct populations of megakaryocytes (MKs) are present in the bone marrow of PTS patients: one is normal whereas the other one consists of small immature MKs undergoing massive lysis. Giant alpha-granules can be detected on blood smears or by electron microscopy in a fraction of the circulating platelets. These alpha granules do not release their content upon thrombin stimulation. A deletion of variable length of the long arm of chromosome 11 is characteristically found in all PTS patients. This deletion includes two genes belonging to the ETS family: ets-1 and fli-1. The critical role played by the fli-1 transcription factor in MK differentiation has been demonstrated both in vitro and in vivo and appears highly relevant to PTS pathophysiology. Fli-1 transactivates several MK-specific genes associated with terminal differentiation, in particular the gene coding for the glycoprotein GPIb (CD42b). Dramatic reduction in MK number, small MKs similar to those seen in PTS patients, and major bleeding have been observed in fli-1-/- knockout mice embryos. Ets-1-/- knockout mice do not present with thrombocytopenia and exhibit an abnormal lymphoid differentiation but a normal MK differentiation, suggesting that the role of ets-1 in PTS is more limited. The mechanisms by which haploinsufficiency of the fli-1 gene leads to dysmegakaryopoiesis remain to be elucidated. It has recently been proposed that transient monoallelic fli-1 expression combined with hemizygous fli-1 deletion in a subgroup of progenitor cells might prevent their differentiation, which could explain the segregation of the PTS MKs into two morphologically distinct populations. As observed in other platelet disorders (for example, thrombocytopenia with absent radii (TAR) Syndrome), platelet counts approach the low normal range in some children as they get older. Recent findings have demonstrated an overlap between PTS and Jacobsen syndrome. Treatment of PTS is symptomatic only. Before using Minirin (desmopressin), which is not recommended for use in children under two years of age, or platelet transfusion, bleeding risk must be evaluated on the basis of the platelet count, degree of bleeding signs, type of surgical procedure, and results of the platelet function studies if they have been performed.
Last update: February 2005