# Epigenetic disruption meets immune deficiency: a case report of ICF syndrome linked to DNMT3B mutation

## TL;DR

A rare genetic disorder called ICF1 was diagnosed in a Palestinian boy through a DNMT3B mutation, and treatment improved his health.

## Contribution

This is the second genetically confirmed ICF1 case from Palestine, contributing to global awareness and genotype–phenotype understanding.

## Key findings

- A homozygous DNMT3B (Arg826Cys) mutation was identified in a Palestinian boy with ICF1 syndrome.
- IVIG therapy reduced infection frequency and improved clinical outcomes in the patient.
- The case reinforces the importance of early diagnosis and management in ICF1.

## Abstract

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare, autosomal recessive primary immunodeficiency, with fewer than 120 cases reported worldwide. ICF type 1 (ICF1) is the most prevalent subtype. Despite its rarity, ICF1 presents a distinct set of clinical features that necessitate increased awareness, particularly in populations with high rates of consanguinity. This case presents a two-year-old Palestinian boy born to consanguineous parents who presented with recurrent respiratory tract infections, facial dysmorphisms, and hypogammaglobulinemia. A comprehensive immunologic evaluation confirmed markedly reduced immunoglobulin levels consistent with an antibody deficiency. Genetic testing identified a homozygous missense mutation in DNMT3B (Arg826Cys), establishing the diagnosis. The patient was started on intravenous immunoglobulin (IVIG) replacement therapy, which was well tolerated and led to a noticeable reduction in infection frequency and an overall clinical well-being improvement. While treatment remains supportive, early recognition and immunologic management can significantly reduce morbidity. This case highlights the importance of early diagnosis and immunologic support in ICF1 syndrome, reinforces genotype–phenotype correlations, and provides valuable insights from an underrepresented region to improve global awareness, diagnosis, and care, being only the second genetically confirmed case from Palestine.