A Rare Case of MHC Class II Deficiency Diagnosed In Utero

Introduction MHC Class II deficiency, also known as Bare Lymphocyte Syndrome type II (BLS II) is a combined immunodeficiency syndrome that results from loss of HLA class II on antigen-presenting cells. There are four distinct groups of BLS II, each resulting from disease causing variants in either class II transactivator (CIITA) or 3 subunits of regulatory factor X. There are less than 100 reported cases of BLS II worldwide. Here we present a case of a newborn who was diagnosed with BLS II prenatally. Case Discussion The mother of an ex–full-term male was referred for an immunology evaluation after diagnostic fetal chorionic villous sampling (CVS) was positive for a homozygous likely pathogenic c.3317+1G>A CIITA variant. Earlier in her pregnancy, a routine prenatal ultrasound found increased nuchal translucency in the fetus, for which she was referred for evaluation by reproductive genetics. Screening for consanguinity was positive. Expanded genetic screening was performed and both parents were found to be carriers of a pathogenic variant c.3317+1G>A in CIITA. Diagnostic CVS confirmed homozygosity for this variant in the fetus. At 39 weeks and 2 days gestational age, the mother delivered a male baby transferred to NICU for further isolation and immunological testing. Confirmatory immune studies including MHC II expression level testing are pending. He is to remain admitted for early-life evaluation for hematopoietic stem cell transplant (HSCT). Discussion The median age of diagnosis of BLS II is at 16 months of age. TREC levels are usually detected with this disease, so it is often missed with newborn screening and usually only diagnosed once the patient starts developing multiple recurrent bacterial infections. The identification of a pathogenic variant in CIITA while in utero resulted in early-life identification of BLS II, improving the chances of survival and prognosis for this patient with early HSCT. This case highlights the advancements in fetal medicine, genetics, and immunologic study techniques that have improved early diagnosis of MHC class deficiencies.