---
title: "IKBKG Frameshift Variant in Pediatric Ectodermal Dysplasia With Immunodeficiency: Case Report and"
id: "frontiers-in-immunology-13-pediatric-ectodermal-dysplasia-with-immunodeficiency-caused-by-a-hemizygous"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-13-pediatric-ectodermal-dysplasia-with-immunodeficiency-caused-by-a-hemizygous"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1831594"
published_at: "2026-09-15T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# IKBKG Frameshift Variant in Pediatric Ectodermal Dysplasia With Immunodeficiency: Case Report and
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-13-pediatric-ectodermal-dysplasia-with-immunodeficiency-caused-by-a-hemizygous
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1831594)
- **Published At:** 2026-09-15T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The available source provides only the article title and journal metadata: a case report and literature review describing pediatric **ectodermal dysplasia** with **immunodeficiency** caused by a hemizygous **IKBKG** frameshift variant. - The article is identified as published in Frontiers in Immunology; no author names, abstract, case details, methods, results, or conclusions are present in the supplied source content. - Critical clinical data typically expected in such a report—patient age, sex, clinical presentation, physical and immunologic findings, infection history, laboratory and imaging results, genetic testing methods, variant nomenclature and pathogenicity evidence, treatment, and outcomes—are not reported in the provided source text. - The supplied content contains site navigation and journal information but no case description, literature synthesis, or specific data to summarize. - Because the source text lacks primary details, no factual statements about the case, the specific variant effect, management, or review findings can be reliably extracted or restated. - Any clinical interpretation, prevalence data, treatment recommendations, or study results cannot be inferred and would require access to the full published article. - Users seeking clinical or research details about **IKBKG**-related ectodermal dysplasia with immunodeficiency should consult the full article at Frontiers in Immunology or contact the journal for the complete text; the supplied source did not include the content necessary for an evidence-based rewrite.
## Clinical Analysis & Structured Key Points
Frontiers | Pediatric ectodermal dysplasia with immunodeficiency caused by a hemizygous IKBKG frameshift variant: a case report and literature review ORIGINAL RESEARCH article Front. Immunol. , 15 September 2026 Sec. Primary Immunodeficiencies Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1831594 Published in Frontiers in Immunology Primary Immunodeficiencies 7 impact factor 11.3 citescore Editor & Reviewers Edited by A K Attila Kumanovics Reviewed by F C Francisco Cammarata-Scalisi R Y Roukaya Yaakoubi Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Table 1 Dynamic Changes in Routine Stool Parameters. View in article Table 2 Dynamic Changes in Blood Cell Analysis and C-Reactive Protein. View in article Table 3 Specific lymphocyte subset data. View in article Table 4 WES genetic testing results for pediatric patients. View in article Table 5 Clinical manifestations, immunological phenotypes, treatment and prognosis of diseases associated with the IKBKG gene. View in article Table 6 Distribution of mutation types. View in article Table 7 Common manifestations of immunological phenotypes. View in article ORIGINAL RESEARCH article Front. Immunol. , 15 September 2026 Sec. Primary Immunodeficiencies Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1831594 Pediatric ectodermal dysplasia with immunodeficiency caused by a hemizygous IKBKG frameshift variant: a case report and literature review Y X Yifan Xuan † X C Xin Chang † Y Y Yanfei Yang Y W Yanfen Wang * Shanxi Bethune Hospital (Shanxi Medical Academy), Third Hospital of Shanxi Medical University, Department of Pediatrics, Shanxi Bethune Hospital, Tongji Shanxi Hospital, Taiyuan, China Article metrics View details Abstract Objective: This case report looks at a child’s ectodermal dysplasia with immunodeficiency ( EDA-ID ), caused by a mutation in the IKBKG gene, and other relevant cases. Methods: A pediatric patient diagnosed with EDA-ID was examined at Shanxi Bethune Hospital in July 2025. Clinical data were systematically collected, and whole-exome sequencing (WES) was performed on blood samples from the patient and their family members to identify potential pathogenic variants. Segregation analysis and a comprehensive literature review were performed. Results: The patient exhibited symptoms including fever, mucoid bloody stools, and atopic dermatitis. WES analysis revealed the presence of a hemizygous variant, designated c.1167dup (p. Glu390ArgfsTer5), within the IKBKG gene. In accordance with the guidelines established by the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genomics Resource (ClinGen), this variant is classified as pathogenic (PVS1+PS4). Conclusion: In pediatric patients with early-onset findings, immunodeficiency should be considered after excluding infections, rheumatic or malignancies. Key clinical features that raise suspicion include sparse hair, reduced sweating, dry skin, recurrent infections, treatment-refractory atopic dermatitis, persistently elevated acute-phase inflammatory markers, and immune dysfunction. Genetic testing facilitates early diagnosis, thereby supporting treatment planning. In this study, we identified a pathogenic IKBKG variant (c.1167dupC) in a pediatric patient with EDA-ID via WES, expanding the current understanding of genotype-phenotype correlations. 1 Introduction Ectodermal dysplasia with immunodeficiency ( EDA-ID ) is a condition resulting from impaired nuclear factor κB (NF-κB) signaling due to genetic mutations or associated defects. Its clinical presentation is diverse and includes ectodermal dysplasia, lymphedema, osteopetrosis, and multiple immunological abnormalities. Patients may experience recurrent infections, diminished antibody response to polysaccharides, hypogammaglobulinemia, hyper-IgM syndrome, impaired natural killer (NK) cell cytotoxicity, and autoimmune disorders ( 1 ). Differential diagnoses include hyper-IgM syndromes, common variable immunodeficiency(CVID), and other combined immunodeficiencies. Diagnosis relies on clinical manifestations, immunological phenotype, and genetic testing. Two genes associated with EDA-ID have been identified: mutations in the IKBKG gene, which encodes the NF-κB essential modulator ( NEMO ), follow an X-linked inheritance pattern ( 2 ); and mutations in the NFKBIA gene, encoding the NF-κB inhibitor α (IκBα), cause autosomal EDA-ID ( 3 ). X-linked EDA-ID (XL-EDA-ID) is a relatively uncommon condition. The c.1167dup mutation in IKBKG has been previously reported; however, the clinical phenotype associated with this recurrent variant is not fully characterized. This report describes a pediatric patient with EDA-ID caused by the IKBKG c.1167dup mutation, further expanding the clinical phenotype associated with this variant. By combining a literature review with this case study, we aim to enhance clinicians’ awareness of this condition and improve early diagnosis. 2 Objectives and methods A four-month-old male infant was admitted to our hospital due to recurrent leukocytosis and bloody stools. After obtaining informed consent from the family, we collected clinical data and drew 5 mL of peripheral blood samples from both the infant and his parents for genetic analysis. We also collected clinical information, including medical history, family history, laboratory findings, imaging studies, and treatment records. A comprehensive literature search was performed using the keywords “ectodermal dysplasia with immunodeficiency”, “X-linked ectodermal dysplasia with immunodeficiency”, “ NEMO-ID ”, and “ IKBKG gene” in CNKI, Wanfang Database, VIP Database, and PubMed from database inception to August 31, 2025. Inclusion criteria were:(1)confirmed IKBKG mutation;(2)clinical diagnosis of EDA-ID, OL-EDA-ID (Osteopetrosis, Lymphedema, Anhidrotic Ectodermal Dysplasia with Immunodeficiency), or isolated immunodeficiency;(3)available clinical or immunological data;(4)age ≤18 years. Only articles published in English or Chinese were included. Exclusion criteria were duplicate publications or lack of original data. The literature screening was conducted in strict accordance with the PRISMA guidelines, and the specific screening procedure is presented in Figure 1 (PRISMA flow diagram). Figure 1 PRISMA flow diagram. 3 Case data and literature findings 3.1 Case presentation Family and personal history: Non-consanguineous parents, no history of infections or infant deaths. The patient was the first-born at 40 +6 weeks of gestation; oligohydramnios was noted at 37 weeks but not addressed. Birth was complicated by grade II amniotic fluid contamination and ecchymoses; platelets and coagulation were normal. The infant received antimicrobial and hemostatic therapy and was discharged. At 7 days of life, eczema developed that was unresponsive to topical therapy. Umbilical cord detachment occurred at 45 days with minor discharge. No perianal abscess was noted. The newborn has completed the screening for four conditions (Phenylketonuria, Congenital Hypothyroidism, Congenital Adrenal Hyperplasia, Glucose-6-phosphate dehydrogenase deficiency) and HIV nucleic acid test was normal. The infant presented with diarrhea at two months of age, with 7 to 10 episodes per day; the stools contained mucus and bloody pus. A thorough stool examination revealed the presence of 3 to 5 red blood cells (RBCs) per high-power field (HPF), along with 10 to 20 white blood cells (WBCs) per HPF. Further investigation was prompted by the patient’s elevated white blood cell count, which exhibited fluctuations and was measured at a range of 15.75-29.53 x 10 9 /L. Given the infant’s concurrent presentation of intractable eczema, the probable etiology was identified as a food protein allergy. Consequently, the therapeutic regimen was modified to encompass lactase, montmorillonite, probiotics, and an amino acid formula. However, the child’s diarrhea showed no improvement, and routine stool examinations continued to– reveal the presence of red and white blood cells. Consequently, the child was admitted to our hospital for treatment at 4 months of age. Upon admission, the patient was examined physically, revealing a height of 68 centimeters, a weight of 6 kilograms, and a BMI of 13.0kg/m 2 (3rd–5th percentile by WHO child growth standards). The anterior fontanelle was observed to be flat and soft, with dimensions measuring approximately 1.5 × 1.5 cm. The subject’s scalp hair and eyebrows were sparse, with no other body hair present. Teeth had not yet erupted, and nails appeared normal. In the course of febrile episodes, the occurrence of sweating was reduced or ceased. The rash was characterized by its diffuse appearance, non-pruritic, and a pale red coloration. It was also noted that the rash exhibited a circular configuration and was located in a superficial layer of the skin. Cardiac, pulmonary, and abdominal examinations revealed no abnormalities. The perianal region exhibited no signs of redness, swelling, or ulceration. Post-admission laboratory monitoring revealed an elevated white blood cell count, with red and white blood cells visible in routine stool examinations. Further diagnostic procedures, including stool culture, did not reveal any signs of a specific infection. Normal platelet and coagulation function levels suggest the absence of coagulation disorders for the time being. Abdominal X-ray and ultrasound revealed no congenital intestinal anomalies. The most probable diagnosis was that of infectious diarrhea, and the child was treated with cefotaxime for the infection. The child’s diarrhea exhibited a marginal improvement, with red and white blood cells in the stool returning to normal levels. However, the fecal occult blood test remained positive. The child developed a fever and diarrhea after contact with a sick family member. Inflammatory bowel disease and immunodeficiency were considered as possible causes. Comprehensive respiratory NGS testing revealed Pneumocystis jirovecii pneumonia and parainfluenza virus type 3 infection. The treatment regimen was adjusted to penicillin combined with cefoperazone/sulbactam. Monitoring of immune function revealed hypogammaglobulinaemia, suggesting immunodeficiency, and the patient was transferred to Beijing Children’s Hospital. During hospitalization, the patient underwent bone marrow aspiration, lumbar puncture, bronchoscopic alveolar lavage and genetic testing. The patient was placed on mechanical ventilation and treated with trimethoprim-sulfamethoxazole for infection and intravenous immunoglobulin (IVIG). Genetic testing results confirmed EDA-ID caused by a mutation in the IKBKG gene. In January 2026, the patient underwent allogeneic hematopoietic stem cell transplantation. Currently, the patient is in good health with no post-transplant complications reported, and further evaluation is scheduled for July 2026. 3.2 Laboratory testing 3.2.1 Routine stool examination and occult blood test (March 18-July 28, 2025) The specific details are provided in Tables 1 and 2 . Table 1 Times Fecal occult blood Leukocytes/HP Red blood cells/HP 2025-07-20 + 20-30 1-3 2025-07-22 + 5-10 3-5 2025-07-23 + 5-10 1-3 2025-07-24 +- 5-10 0-1 2025-07-25 + 0-1 5-10 2025-07-28 + 0 0 Dynamic Changes in Routine Stool Parameters. Table 2 Times WBC*10 9 /L neutrophil% hemoglobin(g/l) Platelets*10 9 /L C-Reactive Protein (mg/l) 2025-03-18 29.53 70.0% 190 342 T; p.Arg1084Ter), inherited from the father (mother wild type). This variant is associated with thyroid secretory disorder type 6(autosomal recessive). It is likely incidental, as no thyroid dysfunction was observed. Limitation: No functional validation(e.g. NF-κB phosphorylation, IκBα degradation, TNF-α stimulation assays)was performed due to the unavailability of frozen samples. The detailed genetic testing results and the Sanger sequencing chromatograms are shown in Table 4 and Figure 2 , respectively. Table 4 Genes Chromosome Nucleotide variation in transcript numbering Genotype Pathogenic classification Mode of inheritance IKBKG chrX:153792583-153792584 exon10 c.1167dup Hemizygous Father: Wild-type Mother: Heterozygous pathogenic X-linked inheritance DUOX2 chr15:45392025 exon25 c.3250C>T Heterozygous Father: heterozygous Mother: wild-type pathogenic Autosomal Recessive WES genetic testing results for pediatric patients. IKBKG (OMIM:300248); DUOX2 (OMIM:606759). Figure 2 Sequencing map of the IKBKG gene in each member of the EDA-ID family. Pediatric patient (hemizygous); Mother (heterozygous); Father (wild-type). Arrows indicate variant sites. 3.3 Literature review The comprehensive literature search identified 56 English-language and 3 Chinese-language publications, reporting 65 EDA-ID patients with IKBKG variants (excluding the present case). Among these, eight cases were identified as OL-EDA-ID , and 11 cases were classified as the non-ectodermal dysplasia subtype, which is characterized by pure immunodeficiency. The c.1167dup mutation identified in this case is one of the most frequently reported pathogenic mutations to date. The detailed list of included references is provided in Table 5 . Table 5 Cases Nucleotide or amino acid alterations Family history EDA Infectious diseases Immunological phenotypes Outcome 1 ( 4 ) c.1117 + 5G>C + – + IgA↓, IgG↓ Death 2 ( 5 ) c.111dupC(p.Met38fsTer48) – – + IgA↓, IgG↓, IgM↑ Death 3 ( 6 ) c.1056-1G>A – – + NK cells↓ IVIG 4 ( 7 ) c.601C>T (p.Gln201Ter, Q201X) + – + – Death 5 ( 8 ) c.931C>G (p.Asp311Glu, D311E) – – + – HSCT 6 ( 9 ) c.956G>A (p.Arg319Gln, R319Q) – – + IgG↑ Treatment for tuberculosis 7 ( 10 ) c.1238A>G (p.His413Arg, H413R) – + + All IgG subclasses↓, B cells↓, NK cells↓ Death 8 ( 11 ) c.1259A>G (p.Ter420Trp, X420W) + + + Impaired TNF-α response Death 9 ( 12 ) c.1259A>G (p.Ter420Trp, X420W) + + + IgG↓, T cell deficiency Death 10 ( 13 ) c.1259A>G (p.Ter420Trp, X420W) + + + IgG↓, lack of antibodies to polysaccharide antigens Death 11 ( 14 ) c.1259A>G (p.Ter420Trp, X420W) + + + Impaired TNF-α response Death 12 ( 15 ) c.1167dupC (p.Glu390fs, E390fs) + + + All IgG subclasses↓, CD3+ T cells↑, CD4+ T cells↑, NK cells↓ HSCT 13 ( 16 ) c.1167dupC (p.Glu390fs, E390fs) + + + IgG↓, NK cell activity↓, B cells↑ HSCT 14 ( 17 ) c.1167dupC (p.Glu390fs, E390fs) + + Unknown – Unknown 15 ( 18 ) c.1167dupC (p.Glu390fs, E390fs) + + + IgA↑, production of polysaccharide-specific antibodies↓ Unknown 16 ( 19 ) c.169G>A (p.Glu57Lys, E57K) – – + IgG↓, specific polysaccharide antibody deficiency, B cells↓ IVIG 17 ( 20 ) c.1167dupC (p.Glu390fs, E390fs) + + + IgG↓ HSCT 18 ( 21 ) c.1167dupC (p.Glu390fs, E390fs) + + + IgG↓ HSCT 19 ( 21 ) c.1167dupC (p.Glu390fs, E390fs) – + Unknown IgG↓, NK cells↓ Death 20 ( 21 ) c.1167dupC (p.Glu390fs, E390fs) – + + IgG↓, CD8+ T cell proportion↓, NK cells↓ Death 21 ( 18 ) c.1250G>T (p.Cys417Phe, C417F) – + + IgA↑, IgM↑, IgG↓, production of polysaccharide-specific antibodies↓ IVIG 22 ( 22 ) c.1171G>A (p.Arg352SerfsTer373, R352Sfs*373) – + + IgG↓, IgM↑ HSCT 23 ( 23 ) c.1027 + 5G>A + + + IgG↑, IgA↓, IgM↓, T cells↑, B cells↓ Unknown 24 ( 24 ) c.944A>C (p.Glu315Ala, E315A) – + + IgG↑, T cells↑ Death 25 ( 25 ) c.916G>A (p.Asp306Asn, D306N) + + + IgA↑ Death 26 ( 26 ) c.1249T>C (p.Cys417Arg, C417R) – + + IgG↓ IVIG 27 ( 18 ) c.1249T>C (p.Cys417Arg, C417R) – + + IgG↓, IgA↓, IgM↑ Death 28 ( 18 ) c.1249T>C (p.Cys417Arg, C417R) – + + IgG↓, NK cells↓ IVIG 29 ( 27 ) c.1171G>T (p.Glu391Ter, E391X) – + + T cells↓, B cells↑ IVIG 30 ( 27 ) c.1171G>T (p.Glu391Ter, E391X) – + + T cells↓, B cells↑ IVIG 31 ( 27 ) c.1171G>T (p.Glu391Ter, E391X) – + + T cells↓, B cells↑ IVIG 32 ( 24 ) c.761G>A(p.Arg254Gln, R254Q) – – + IgA↓, IgG↓, B cells↓, CD4+ T cells↓ Death 33 ( 28 ) c.1117 + 1G>A – – + IgA↑, IgM↓, memory B cells↓ Death 34 ( 27 ) c.1171G>T (p.Glu391Ter, E391X) – + + T cells↓, B cells↑ IVIG 35 ( 18 ) c.1171G>T (p.Glu391Ter, E391X) – + + IgA↓, IgG↓, IgM↑ Death 36 ( 29 ) c.458T>G (p.Leu153Arg, L153R) – + + NK cell cytotoxicity deficiency HSCT 37 ( 18 ) c.1171G>T (p.Glu391Ter, E391X) – + + IgA↓, IgG↓, IgM↑ Death 38 ( 30 ) c.399 + 850_674dup (Dupfrom intron 3 to exon 6) + + + IgG↑, IgA↑, IgM↓, CD4+ T cells↓ Death 39 ( 30 ) c.399 + 850_674dup (Dupfrom intron 3 to exon 6) + + + T cell proliferation↓ Death 40 ( 24 ) Rearrangement from Intron 4-8 – + + All Ig subclasses↓ Unknown 41 ( 24 ) c.597G>A (A174_K224del) – + + IgA↓, IgG↓, IgM↑ Unknown 42 ( 31 ) c.74_77delACGT(p.His25ArgfsTer14) – – + IgA↓, IgG↓, IgM↑
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