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Paris-Trousseau thrombocytopenia

General Information (adopted from Orphanet):

Synonyms, Signs:	TCPT CHROMOSOME 11q23 DELETION SYNDROME
Number of Symptoms	19
OrphanetNr:	851
OMIM Id:	188025
ICD-10:	D69.4
UMLs:	C1861178 C1956093
MeSH:	C538617
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	No data available.
Inheritance:	Sporadic [Omim]
Age of onset:	Neonatal Infancy [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Partial deletion of the long arm of chromosome 11
-Rare developmental defect during embryogenesis
-Rare genetic disease
Rare hemorrhagic disorder due to a constitutional thrombocytopenia
-Rare genetic disease
-Rare hematologic disease

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000243)	Trigonocephaly		40 / 7739
2	(HPO:0000347)	Micrognathia		426 / 7739
3	(HPO:0000508)	Ptosis		459 / 7739
4	(HPO:0001249)	Intellectual disability		1089 / 7739
5	(HPO:0009466)	Radial deviation of finger		101 / 7739
6	(HPO:0002021)	Pyloric stenosis		51 / 7739
7	(HPO:0001626)	Abnormality of the cardiovascular system	Frequent [Orphanet]	73 / 7739
8	(HPO:0003010)	Prolonged bleeding time		88 / 7739
9	(HPO:0001892)	Abnormal bleeding		85 / 7739
10	(HPO:0001873)	Thrombocytopenia		224 / 7739
11	(MedDRA:10058668)	Clinodactyly		91 / 7739
12	(OMIM)	Hemorrhagic diathesis, mild		1 / 7739
13	(OMIM)	Giant platelet alpha granules (peripheral blood)		1 / 7739
14	(MedDRA:10027120)	Megakaryocytes increased		1 / 7739
15	(OMIM)	Chromosome 11q23.3 deletion		1 / 7739
16	(HPO:0030084)	Clinodactyly		90 / 7739
17	(HPO:0012758)	Neurodevelopmental delay	Frequent [Orphanet]	949 / 7739
18	(HPO:0003745)	Sporadic		131 / 7739
19	(OMIM)	Increased micromegakaryocytes (bone marrow)		1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

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 ... 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. Breton-Gorius et al. (1995) described congenital dysmegakaryopoietic thrombocytopenia associated with giant platelet alpha-granules in a mother and child with 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.

Symptoms & Signs

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