CD4+ CD31+ recent thymic emigrants in CHD7 haploinsufficiency (CHARGE syndrome): A case

Lymphocyte counts <2000 cells/μL are associated with early death in infants with CHARGE (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness) syndrome and CHD7 haploinsufficiency. Absence of recent thymic emigrants is also accompanied by an Omenn-like syndrome and infant death in CHD7 haploinsufficiency. Studies positively identifying recent thymic emigrants, in relation to CHD7 haploinsufficiency, are non-existent. Thirty two months of flow-cytometric work-up of an athymic (evaluated by four chest X-rays) infant, with a novel CHD7 deletion, demonstrated sparse (<50 cells/mm3) but continuous egress of recent thymic emigrants (CD3+ CD4+ CD45RA+ CD45RO− CD31+) and homeostatic lymphocyte expansion. Infectious or autoimmune episodes (e.g., Omenn-like syndrome) were not detected (despite lymphocyte counts <2000 cells/μL) and excellent vaccination (tetanus, Haemophilus influenzae type B and pneumococcal conjugate vaccines) and proliferation (anti-CD3 and anti-CD28 stimulated) responses were recorded. Her CD4+ T cells displayed Gaussian distributed TCR (CDR3) spectratypes (22 functional Vβ families). Her CD4+ T cell profile was also characterized by a slightly increased proportion CD4+ CD25+ FoxP3+ T cells. Since CD3+ CD4+ CD45RA+ CD45RO− CD31+ RTE are reported to be TCR diverse and to contain regulatory T cells, we found it important to report that continuously reduced numbers of CD3+ CD4+ CD45RA+ CD45RO− CD31+ RTE, in the context of CHD7 haploinsufficiency and despite severe lymphopenia, is consistent with an uneventful clinical outcome.