Ectodermal dysplasias (ED) are genodermatoses sometimes associated with immune deficiency (ED-ID) usually related with variants in genes of the NF-κB pathway, namely IKBKG (NEMO) and NFKBIA (IKB-α). The absence of mutations in these genes represent a challenge in the clinical management of ED-ID.
We present a 14-year-old male with ED-ID characterized by recurrent sinopulmonary infections (with onset at 4 years old), celiac disease and a family history with 2 deceased siblings in the neonatal period. From the immunological standpoint, he presented a selective IgA deficiency, with decreased switched memory B cells and poor response to polysaccharide antigens despite multiple boosters. Additionally, he also presented a persistent low value of C3-C4 although functional complement studies were normal. Prophylactic antibiotics were started initially but due to the persistence of infections and a worsening in his hearing, he was started on immunoglobulin replacement (IgR) with a favorable response. Sanger sequencing of IKBKG and NFKBIA showed no variant. Whole exome sequencing (WES) revealed the presence of 2 highly relevant heterozygous variants: a missense variant in WNT10A (known to cause ED) and a frameshift variant in IRF2BP2 (p.Glu253fs), known to underlie primary antibody deficiencies Patients with ED-ID represent a challenge in both diagnosis and management as there is a wide phenotypic variability in the clinical presentation and multiple treatment options going from IgR to hematopoietic stem cell transplantation. In this case, by expanding the assessment through WES, we were able to document a two genes etiology that explains the phenotype of our patient and clarify the lack of involvement of ED in the immune phenotype. Additionally, given the important role of IRF2BP2 in the Jak-STAT pathway, the documentation of this mutation could enable the use of Jak-inhibitors to treat autoimmune complications that may present in the future.