CGRA5: IMMUNODEFICIENCY WITH RING CHROMOSOME 21

Abstract

Ring chromosome 21 is a rare complex chromosomal deletion syndrome presenting with a variable phenotype which can include failure to thrive, hypotonia, craniofacial abnormalities, and cognitive impairment. Rare patients demonstrate hypogammaglobulinemia, potentially due to loss of a gene within the deleted segment. We report a child with ring chromosome 21 presenting with many of the associated syndromic features. This case also demonstrates panhypogammaglobulinaemia and impaired T cell function, presenting with recurrent purulent otitis media and fungal infections of the skin and renal tract. Chromosomal studies revealed 46 XX r21; 45 XX −21 mosaicism with 37% of cells containing ring chromosome 21 and the remainder being monosomy 21. She had very low IgG, absent IgA and IgE and variable IgM and a low B cell count of 6%, with no memory B cells. She had a persistent leucocytosis with a predominance of eosinophils and monocytes and an abnormal PHA. Hypogammaglobulinaemia with Ring Chromosome 21 has been previously seen in single case reports. Susceptibility to fungal infection with reduced T cell function has not been previously reported to be associated with this condition. Loss of genetic material due to formation of the ring chromosome does not include genes implicated in other defined monogenic immunodeficiencies, indicating that Ring Chromosome 21 may be an independent cause of an immunodeficiency syndrome.