[CIS-PAGID] 22q12.3 defect and poor wound healing

[Larkin, Allyson]

Dear Colleagues:


We have a 7 week old female with a 22q12.3 defect who has had poor wound healing after cardiothoracic surgery.  Immunology was asked to comment on MSSA bacteremia and mediastinitis. On review of the literature, defects in 22q13.1 are associated with “neutrophil immunodeficiency syndrome” caused by mutation in the RAC2 gene (OMIM 602049).  Her clinical history is outlined below. We would appreciate any thoughts related to her clinical presentation and her 22q12.3 defect; specifically related to the possibility of a phagocytic/neutrophil disorder.

·        Born at term to non consanguineous parents with hemihypertrophy and capillary vascular malformations. Also had a portal venous thrombosis (? Line related).

·        Known prenatal cardiac anomalies (double inlet left ventricle, hypoplastic right ventricle, large bulboventricular foreman, malposed great vessels, sub-pulmonic stenosis and valvar pulmonic stenosis)

·        Had a Blalock-Taussig shunt procedure 6 weeks ago (day of life 4). Operative report commented on presence of a thymus.

·        Discharged to home but readmitted with fever.

·        Taken back to the operating room and large amount of pus found on exploration. Wound cultures positive for MSSA and gram stain showed many neutrophils.  Blood cultures also positive for MSSA.

·        No omphalitis or delayed cord separation.

·        A genetic workup found a defect on the 22q12.3 region of the long arm of chromosome 22.

·        Family history significant for XLA in a second cousin.

·        Laboratory studies: (CBCs do not show persistent leukocytosis or lymphopenia, NOBA and CH50 pending)
IgA                                                                    21 Milligrams/deciliter
IgG                                                                    446 Milligrams/deciliter
IgM                                                                   41 Milligrams/deciliter
% T-Cells (CD3)                                               74 %  High
Total T-Cells (CD3)                                        4606 /cumm  High
% Helper Cells (CD4)                                    59 %  High
Total Helper Cells (CD4)                              3683 /cumm  High
% Suppressor Cells (CD8)                            14 %  Low
Total Suppressor Cells (CD8)                      894 /cumm
% B-Cells (CD19)                                         18 %  Low
Total B-Cells (CD19)                                     1143 /cumm
% NK Cells (CD16/CD56)                              7 %
Total NK Cells (CD16/CD56)                        419 /cumm
Helper/Suppressor Ratio                             4.12   High

                              Karyotype 22q12.3(32,191,531-532,537,463)x1.


Allyson Larkin, MD
Children's Hospital of Pittsburgh