Paris-Trousseau syndrome

Overview

Paris-Trousseau syndrome is a rare genetic disorder characterized primarily by a lifelong bleeding tendency due to a platelet function defect. It is often associated with a broader chromosomal abnormality known as Jacobsen syndrome, which results from a partial deletion of the long arm of chromosome 11 (11q). Individuals with Paris-Trousseau syndrome typically have a reduced number of platelets (thrombocytopenia) and abnormal platelet morphology, leading to impaired clot formation and prolonged bleeding times. The syndrome is named after the French physicians who first described the condition. While bleeding is the hallmark symptom, it is often accompanied by other congenital anomalies seen in Jacobsen syndrome, such as developmental delays, heart defects, and facial dysmorphisms.

Causes

Paris-Trousseau syndrome is caused by a deletion on chromosome 11 at the long arm (11q23.3), often as part of Jacobsen syndrome. This deletion results in the loss of multiple genes, including FLI1, a transcription factor crucial for normal platelet development and function. The absence or reduced expression of FLI1 disrupts megakaryocyte maturation—cells responsible for producing platelets—and leads to the formation of abnormally large, dysfunctional platelets. The condition is typically not inherited but arises de novo (sporadically) during embryonic development. In rare cases, it may be passed from an affected parent with a balanced chromosomal rearrangement.

Symptoms

The primary clinical manifestation of Paris-Trousseau syndrome is a bleeding disorder due to platelet abnormalities. Symptoms may range from mild to severe and include:

Hematologic Symptoms

• Easy bruising: Even with minimal trauma

• Prolonged bleeding: After cuts, surgical procedures, or dental work

• Nosebleeds (epistaxis): Frequent and difficult to control

• Bleeding gums: Especially during tooth brushing or dental procedures

• Menorrhagia: Heavy menstrual bleeding in adolescent and adult females

• Gastrointestinal bleeding: In rare, severe cases

Associated Features from Jacobsen Syndrome

Because Paris-Trousseau syndrome often occurs as part of Jacobsen syndrome, additional symptoms may include:

• Facial anomalies: Such as a broad nasal bridge, drooping eyelids (ptosis), and small lower jaw (micrognathia)

• Congenital heart defects: Including ventricular septal defect or hypoplastic left heart syndrome

• Developmental delays: Intellectual disability and motor skill impairment

• Behavioral issues: ADHD, anxiety, and autistic traits

• Immunodeficiency: Increased susceptibility to infections in some cases

Diagnosis

Diagnosis of Paris-Trousseau syndrome is based on a combination of clinical findings, blood tests, and genetic analysis. Steps include:

• Complete blood count (CBC): Typically reveals thrombocytopenia (low platelet count)

• Peripheral blood smear: Shows large, immature platelets with abnormal granules

• Platelet function tests: Demonstrate impaired platelet aggregation and response to stimuli

• Genetic testing: Chromosomal microarray or karyotyping confirms 11q deletion and helps diagnose Jacobsen syndrome

• Flow cytometry and molecular studies: May be used to assess FLI1 expression and megakaryocyte markers

• Family history and physical exam: To identify any associated congenital anomalies or dysmorphic features

Treatment

Treatment of Paris-Trousseau syndrome focuses on managing the bleeding disorder and addressing associated complications. A multidisciplinary approach is often required, involving hematologists, cardiologists, geneticists, and developmental specialists.

Hematologic Management

• Bleeding prevention: Avoidance of trauma and careful monitoring during surgeries or dental work

• Platelet transfusions: Used during active bleeding episodes or before invasive procedures

• Desmopressin (DDAVP): May be considered in some cases to improve platelet function

• Antifibrinolytics: Such as tranexamic acid to reduce bleeding, especially for mucosal bleeding

• Avoidance of NSAIDs: Such as aspirin or ibuprofen, which can worsen platelet dysfunction

Supportive Care for Associated Features

• Developmental therapy: Early intervention programs for speech, motor, and cognitive delays

• Cardiac care: Monitoring and surgical correction of congenital heart defects if needed

• Educational support: Individualized learning plans for children with intellectual disabilities

• Immunological support: Monitoring and management of infections in cases with immune deficiency

Prognosis

The prognosis of Paris-Trousseau syndrome depends on the severity of the bleeding disorder and the presence of additional anomalies related to Jacobsen syndrome. While the platelet defect typically persists throughout life, many individuals can manage bleeding episodes effectively with proper precautions and medical support. Severe bleeding events are relatively uncommon with careful care, but the risk increases during surgery or trauma.

In cases associated with Jacobsen syndrome, developmental delays, cardiac defects, and immune dysfunction may significantly impact quality of life and long-term outcomes. Early diagnosis, regular follow-up, and a coordinated care team greatly enhance prognosis and help individuals with Paris-Trousseau syndrome lead safer and more functional lives.