FOXN1 Gene Considerations in Severe Combined Immunodeficiency Treatment in Children

Forkheadbox N1 (FOXN1) gene mutation in humans is a rare cause of thymic hypoplasia and T cell immunodeficiency. This gene is the master transcriptional regulator of thymic epithelial cells and disruptions have been described in consequence to a variety of antepartum complications. FOXN1 mutation-mediated immune deficiency is typically associated with severe combined immunodeficiency and alopecia universalis (SCID/NUDE phenotypes) with homozygous alterations in human animal models. Less common, however, FOXN1 alterations can occur in a heterozygous form and provide a distinct phenotype of severe combined immunodeficiency (SCID) without alopecia. Here, we present one such case of a Caucasian child born with heterozygous FOXN1 mutation, first presenting with undetectable T cell levels at newborn screen. He was confirmed to have FOXN1 immunodeficiency in the heterozygous form through genetic testing. Early identification and initiation of appropriate interventions are crucial to reduce mortality from opportunistic pathogens associated with immunodeficiency. Furthermore, we need to appreciate the less common presentations of established diseases among young patients.