LAUSR

To the Editor: Immunodeficiency, centromeric instability and facial anomalies syndrome (ICF) is a rare autosomal recessive condition (OMIM 242860) characterized by pericentromeric chromosome instability and a heterogeneous clinical presentation of recurrent infections, neurologic abnormalities, and facial dysmorphism (hypertelorism, macroglossia, and micrognathia) [1]. In ICF syndrome, defects in DNA methylation at the pericentromeric regions of chromosomes 1, 9, and 16 lead to cytogenetic abnormalities which are prone to breakage [1–3]. Pathogenic variants in four genes have been recognized to date; DNA methyltransferase 3B gene (DNMT3B) causing ICF1, Zinc-finger and BTB domain-containing 24 gene (ZBTB24) causing ICF2, and cell division cycle associated 7 gene (CDCA7) and helicase lymphoid-specific gene (HELLS) causing ICF3 and ICF4, respectively [2]. The most common subtype, affecting approximately 50% of patients, is ICF1 [1]. Immunologic abnormalities in ICF1 result from this epigenetic dysregulation and include defective lymphocyte differentiation, activation, and migration, as evidenced by absent CD19CD27 class switched memory (CSM) B cells, hypogammaglobulinemia, and sub-optimal T cell proliferation with antigen stimulation. Subsequently, patients suffer from recurrent pyogenic infections, opportunistic infections, and failure to thrive [3–5]. Treatment for the immunologic manifestations of ICF1 includes early immunoglobulin replacement and prophylaxis for opportunistic organisms; however, recurrent infections frequently lead to shortened lifespan, with affected patients rarely surviving beyond the second decade [4]. The only curative option for the immunodeficiency associated with ICF1 is hematopoietic cell transplant (HCT), which has been reported in less than 10 cases of ICF1 worldwide [3, 6–8]. All previously reported patients seemingly had successful correction of their hypogammaglobulinemia and reported full donor chimerism following either myeloablative or reduced intensity conditioning (RIC); however, data regarding long-term follow up after transplant is limited. Herein, we describe the case of a Caucasian male who presented at age 6 months with recurrent infections, was subsequently diagnosed with ICF1 syndrome, and underwent HCT at 22 months of life with immune