D1.418 - An EBP Gene Variant in a Child with Immunodeficiency: A Case from the Chondrodysplasia Pontata Spectrum

Primary immunodeficiencies are a heterogeneous group of diseases characterized by recurrent infections in early childhood. In syndromic cases, the association of infections with structural anomalies may delay diagnosis. Chondrodysplasia punctata is a rare syndrome spectrum characterized primarily by skeletal system anomalies, and its X-linked form is associated with variants in the EBP gene. This report presents a pediatric case with an EBP gene variant and humoral immunodeficiency findings.

This study is a case presentation of a retrospective review of the clinical, immunological, radiological, and genetic data of a single pediatric patient evaluated due to recurrent infections and syndromic findings.

A five-year-old male patient was evaluated for upper and lower respiratory tract infections that had increased in frequency over the past year. His medical history included intrauterine growth retardation and a history of surgery for patent ductus arteriosus. Anthropometric assessment revealed a height measurement below −2 SDS. Physical examination revealed a dysmorphic facial appearance accompanying growth retardation; sparse hair and eyebrows, low-set and protruding ears, and a short and broad nape of the neck were present. Respiratory, cardiovascular, and abdominal system examinations were normal.

Laboratory tests revealed panhypogammaglobulinemia. Inadequate specific antibody responses were observed. Flow cytometric analysis showed low CD19⁺ B cell ratios and an inverted CD4/CD8 ratio. Radiological examinations revealed metaphyseal irregularities in the distal radius and ulna, as well as ovoid shaping of the vertebrae. Next-generation sequencing analysis identified a hemizygous missense variant in the EBP gene. Based on the combined clinical and laboratory findings, the patient was diagnosed with common variable immunodeficiency and started on intravenous immunoglobulin replacement therapy. Follow-up after treatment showed a marked decrease in the frequency and severity of infections.

This case demonstrates that immunodeficiency may accompany the clinical picture in the spectrum of EBP-associated chondrodysplasia punctata. In children presenting with syndromic skeletal anomalies and dysmorphic findings, infections should not be attributed solely to anatomical causes; detailed immunological evaluation and long-term follow-up are crucial for early diagnosis and appropriate treatment.