[P3-155] FOXP3 mutation in a patient with proportional microcephaly and developmental delay
Most cases of proportional microcephaly with growth failure and developmental delay have a genetic or metabolic etiology. Whole-exome sequencing (WES) has recently uncovered many causative genes and has also broadened the phenotypic spectrum of each gene. The present study applied WES to a boy with proportional microcephaly, growth failure, developmental delay, and atopic dermatitis, which reveal an unexpected frame-shift mutation (c.1248_1253delinsCT, NM_014009.3; p.Lys416Asnfs, NP_054728.2) in the forkhead box P3 gene (FOXP3). Mutations of this gene are known to result in immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, whose clinical triad comprises (i) chronic enteropathy resulting in protracted diarrhea, (ii) eczematous dermatitis, and (iii) autoimmune endocrinopathy such as type 1 diabetes mellitus and thyroiditis. Mutation of FOXP3 on the X chromosome was reverified by Sanger sequencing in the proband and his carrier mother. Flow-cytometry expression study of FOXP3 in peripheral white blood cells showed that the mean fluorescence intensity of FOXP3 was lower in the proband than in a normal control. We report a mild form of IPEX syndrome presenting with proportional microcephaly, failure to thrive, developmental delay, seizures, atopic dermatitis, and chronic iron-deficiency anemia, but without protracted diarrhea or recurrent major infections. A particularly notable observation was that his late-childhood-onset seizures were aggravated by hypercapnic respiratory acidosis and had progressed to life-threatening status epilepticus. This case warns clinicians of the hazard of respiratory failure in IPEX patients. In addition, our patient had developmental delays in gross and fine motor functions that need to be investigated further in other IPEX patients.