SUMMARY
1. Rubinstein-Taybi syndrome is characterized by the following clinical features:
-Broad thumbs and great toes
-Characteristic facial features
-Short stature
-Developmental delay
-Cardiac abnormalities
-Increased susceptibility to infections
2. Immunologic abnormalities reported in patients include T cell lymphopenia, thymic hypoplasia, impaired delayed cutaneous hypersensitivity response, and impaired specific antibody response.
3. Microdeletions and truncating mutations in the CREB-binding protein (CBP) gene are found in approximately 40-60% of patients. Mutations in the EP300 gene have been reported in a small number of patients.
4. Patients with specific antibody deficiency may benefit from prophylactic antibiotic therapy or immunoglobulin replacement therapy.
OVERVIEW
Rubinstein-Taybi syndrome is characterized by the following clinical features:
-Broad thumbs and great toes
-Characteristic facial features
-Short stature
-Developmental delay
-Cardiac abnormalities
-Increased susceptibility to infections
Immunologic abnormalities reported in patients include T cell lymphopenia, thymic hypoplasia, impaired delayed cutaneous hypersensitivity response, and impaired polysaccharide antibody response.
Microdeletions and truncating mutations in the CREB-binding protein (CBP) gene are found in approximately 40-60% of patients. Mutations in the EP300 gene have been reported in a small number of patients.
EVALUATION
Step 1: Immune Evaluation
-IgG, IgM, IgA,
-Specific antibody responses to vaccine antigens
-Lymphocyte subset enumeration by flow cytometry (CD3, CD4, CD8, CD19, CD16/56)
-In vitro T cell proliferation to Mitogens
-Immunoglobulin levels are typically normal
-Responses to both protein antigens (tetanus and diphtheria) as well as polysaccharide antigens (pneumovax) should be evaluated. Impaired specific antibody responses have been reported in patients.
-T cell lymphopenia has been reported in patients.
-Decreased T cell function may be present.
Step 2: Gene Sequencing
-CREBBP gene sequencing
-Genetic testing for CREBBP mutations is commercially available at a number of testing sites (ex. Gene Dx). However it should be noted that mutations in this gene are only found in 40-60% of cases.
MANAGEMENT
Patients with specific antibody deficiency may benefit from prophylactic antibiotic therapy or immunoglobulin replacement therapy.