SUMMARY

 

 

1.  Kabuki syndrome is a multi-system autosomal dominant disorder which derives its name from the resemblance of patients to the actors in traditional Japanese Kabuki theater.

 

2.  The syndrome is characterized by the following clinical features: 

 

Short stature
Developmental delay
Congenital heart disease
Skeletal anomalies
Cleft Palate
Distinct facial features
Recurrent infections (60%)

 

3.  The unique facial features include long palpebral fissures with eversion of the lateral portion of the lower eyelids, prominent eyelashes, arching of the eyebrows with sparse lateral third, ptosis, large protuberant ears, and open mouth with tented upper lip. 

 

4.  Immunodeficiency has been reported in Kabuki syndrome and includes hypogammaglobulinemia (low IgG and IgA) as well as impaired specific antibody response.  

 

5.  Autoimmune hemolytic anemia and ITP has also been reported in patients. 

 

6.  Approximately 70% of patients with disease carry a mutation in the MLL2 gene which encodes for a Trithorax-group histone methyltransferase. 

 

 

 

 

 

                                                                                                               

OVERVIEW

      

 

    Kabuki syndrome is a multi-system autosomal dominant disorder which derives its name from the resemblance of patients to the actors in traditional Japanese Kabuki theater.
    
     The syndrome is characterized by the following clinical features: 

Short stature
Developmental delay
Congenital heart disease
Skeletal anomalies
Cleft Palate
Distinct facial features
Recurrent infections (60%)

 

      The unique facial features include long palpebral fissures with eversion of the lateral portion of the lower eyelids, prominent eyelashes, arching of the eyebrows with sparse lateral third, ptosis, large protuberant ears, and open mouth with tented upper lip. 

 

      Immunodeficiency has been reported in Kabuki syndrome and includes hypogammaglobulinemia (low IgG and IgA) as well as impaired specific antibody response.  Autoimmune hemolytic anemia and ITP has also been reported in patients. 

 

      Approximately 70% of patients with disease carry a mutation in the MLL2 gene which encodes for a Trithorax-group histone methyltra

 

 

 

                                 

EVALUATION

 

 Step 1:  Immune Evaluation

 

-IgG, IgM, IgA, 
-Specific antibody responses to vaccine antigens

-Low IgG and IgA levels have been reported in patients.
-Responses to both protein antigens (tetanus and diphtheria) as well as polysaccharide antigens (pneumovax) should be evaluated.  Impaired specific vaccine responses have been reported in patients.

 


Step 2:  Gene Sequencing  


-MLL2 gene sequencing

-Genetic testing for MLL2 mutations is commercially available at a number of testing sites. However it should be noted that MLL2 gene mutations are only found in 70% of cases.  Thus, a negative test does not exclude Kabuki syndrome. 

 

 

 

                                                                   

MANAGEMENT

          

      For patients with hypogammaglobulinemia and recurrent sinopulmonary infections, a trial of prophylactic antibiotics may be considered.  For patients with a CVID phenotype (low IgG and impaired specific antibody response) immunoglobulin replacement therapy should be considered. 

                                                                           

 

 

 

 

 

RESOURCES

 

Diagnostic Resources


1.  UNIV. CHICAGO - MLL2 sequencing 

2.  BOSTON U. - MLL2 sequencing 

 

 

 

Literature Resources

 

1.  Adam 2005 
     Kabuki Syndrome (review)
    

2.  Hoffman 2005 
     Immune abnormalities in Kabuki Syndrome 
 

3.  Ng 2010 
     MLL2 mutations cause Kabuki Syndrome