To investigate the clinical characteristics, genetic features, and diagnostic and therapeutic strategies of deficiency in ELF4, X-linked (DEX).

A child with DEX who was hospitalized at the Children′s Hospital of Soochow University in September 2022 was enrolled as the proband. Clinical data, including clinical manifestations, laboratory findings, imaging features, genetic testing results, treatment, and follow-up outcomes, were retrospectively analyzed. Whole-exome sequencing (WES) was performed to identify ELF4 gene variants, which were subsequently confirmed by Sanger sequencing, and their pathogenicity was evaluated according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). A literature search was conducted using the keywords " " ELF4 deficiency" and " ELF4 mutation" in Chinese and English across the Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Medical Journal Network, and PubMed databases. The search period ranged from inception to December 30, 2025. This study was approved by the Medical Ethics Committee of the Children′s Hospital of Soochow University (Approval No. 2024CS087), and written informed consent was obtained from the patient′s guardian.

①The proband was a 4-year-10-month-old boy, the second-born of a twin pregnancy. His main clinical manifestations included perianal abscess, recurrent fever, abdominal pain, and oral ulcers. Colonoscopy revealed a large ulcer in the ileocecal region. WES identified a missense variant in the ELF4 gene (NM_001421.3), c.799C>T (p.R267W), located within the ETS domain. Sanger sequencing confirmed that the variant was maternally inherited, and it was classified as likely pathogenic according to the ACMG guidelines. Immunological evaluation indicated abnormalities in certain T- and B-lymphocyte subsets. The patient′s condition gradually improved following combined treatment with glucocorticoids, immunosuppressants, and biologic agents. His monozygotic twin brother presented only with recurrent oral ulcers and had milder symptoms. ②Literature review: A total of 29 pediatric patients with DEX were included. Among them, 89.7% (26/29) were male, and 64.3% (18/28) had disease onset at ≤6 years of age. The main clinical manifestations included oral ulcers (86.2%, 25/29), gastrointestinal symptoms (69.0%, 20/29), and fever (58.6%, 17/29). Glucocorticoids and biologic agents were the main therapeutic options. Overall, 72.4% (21/29) of patients achieved clinical remission after treatment, of whom 76.2% (16/21) required combination therapy. One patient maintained remission without medication, and one patient died due to multiple lymphomas. A total of 23 distinct ELF4 gene variants were identified in the 29 patients, with missense and frameshift variants being the most common, each accounting for 39.1% (9/23). Notably, 87.0% (20/23) of the variants involved the ETS domain, and variants affecting this domain were more likely to be associated with an autoinflammatory phenotype.

DEX exhibits marked clinical heterogeneity, and most patients require combination therapy for disease control. The disease predominantly presents with autoinflammatory features and may manifest as inflammatory bowel disease-like or Behçet′s disease-like phenotypes. ELF4 variants are mainly clustered in the ETS domain and variants involving the ETS domain of ELF4 may be associated with an autoinflammatory phenotype. Given that effective disease control often requires multi-drug therapy, early genetic testing should be considered in patients with early onset, atypical clinical manifestations, or poor response to treatment to establish a definitive diagnosis and guide individualized therapy.