Thrombocytopenia, Paris-Trousseau Type

A number sign (#) is used with this entry because of evidence that the Paris-Trousseau type of thrombocytopenia (TCPT) is a contiguous gene deletion syndrome.

Clinical Features

Favier et al. (1993) reported the cases of a 30-year-old woman and her 1-year-old son with chronic thrombocytopenia associated with mild hemorrhagic complications. The platelets contained giant, red-staining granules, and in the bone marrow megakaryocytes were increased with many micromegakaryocytes. Since platelet life span was normal, Favier et al. (1993) interpreted the results as indicative of ineffective platelet production. Both patients had a deletion of band 11q23. The mother showed unusual facial features, including hypertelorism, long philtrum, and low-set ears. Mental retardation was characterized by an inability to count, although she could read and write. At the age of 10 years, she was operated on for aortic isthmic stenosis (coarctation) without hemorrhagic complications. The son showed intrauterine growth retardation and had the same dysmorphologic facial features as the mother but also had hepatomegaly and fifth finger syndactyly. Neither thrombocytopenia nor chromosomal aberrations were found in other members of the family. Psychomotor development at one year was retarded. Favier et al. (1993) noted that Wardinsky et al. (1990) had examined reports of 35 patients with deletion of 11q23. Thrombocytopenia was associated in 47% of the cases. In the mother and son reported by Favier et al. (1993), Breton-Gorius et al. (1995) identified a terminal deletion of 11q.

Using electron microscopy to examine the platelets of an infant with an 11q23.3-qter deletion and clinical features of Jacobsen syndrome (147791), Krishnamurti et al. (2001) identified giant alpha-granules identical to those described in Paris-Trousseau syndrome. They suggested that TCPT may be a variant of Jacobsen syndrome and that the thrombocytopenia in all cases of 11q23.3 deletion is due to dysmegakaryopoiesis, with formation of giant alpha-granules during prolonged residence in the bone marrow.

Favier et al. (2003) reported 10 unrelated children with deletions of 11q23 who had abnormal platelets with giant alpha-granules on peripheral blood smear and dysmegakaryopoiesis with many micromegakaryocytes on bone marrow examination. Clinical characteristics in addition to thrombocytopenia included mental retardation, facial dysmorphism, clinodactyly, and pyloric stenosis. Nine of the 10 children were found to be heterozygous for a deletion of the FLI1 gene (193067). Favier et al. (2003) noted clinical, hematologic, and cytogenetic similarities between this cohort of patients and patients with Jacobsen syndrome and stated that their findings demonstrated clear overlap between the 2 syndromes.

Raslova et al. (2004) showed that lentivirus-mediated overexpression of FLI1 in CD34-positive (142230) cells of patients with TCPT restored megakaryopoiesis in vitro, indicating that FLI1 hemizygous deletion contributes to the hematopoietic defects in the disorder. FISH analysis on pre-mRNA and single-cell RT-PCR revealed FLI1 expression to be mainly monoallelic in CD41-positive (see 607759)/CD42-negative progenitors, whereas it was predominantly biallelic in the other stages of megakaryopoiesis. In TCPT cells, the hemizygous deletion of FLI1 generated a subpopulation of CD41-positive/CD42-negative cells completely lacking FLI1 transcription. Raslova et al. (2004) proposed that the absence of FLI1 expression in those CD41-positive/CD42-negative cells might prevent their differentiation, resulting in the segregation of the TCPT megakaryocytes into 2 subpopulations: one normal and the other composed of small immature megakaryocytes undergoing massive lysis, presumably originating from FLI1-positive and FLI1-negative CD41-positive/CD42-negative cells, respectively.