IPEX syndrome (Immune dysregulation, polyendocrinopathy, enteropathy x-linked syndrome) is characterized by autoimmune manifestations in multiple organs, particularly skin, gut, and endocrine systems. Mutations in the FOXP3 gene lead to dysfunction of T regulatory cells and an array of phenotypical manifestations. We present a child with previously undescribed neurological manifestations, very mild endocrinology and gastrointestinal symptoms, and severe pruritis leading to localized inguinal self-induced ulceration and genital enlargement.
Methods: Whole Exome Sequencing performed by Gene Dx.
This patient presented at 22 months of age with decreased interactivity, anorexia with weight loss, and abnormal gait. He had regression of milestones including refusal to walk and talk, scattered erythematous plaques and extreme pruritis localized the genital area, followed by a period of fevers without identified focus. Neurological symptoms slowly improved with a course of steroids. Multidisciplinary workup found no endocrinopathies, enteropathy, neurological or infectious etiologies. hyperkeratotic psoriasiform hyperplasia without spongiosis on skin biopsy. IgE 9527, IgG 4 163, Normal IgM and IgA. Continued itching led to ulceration of the perineal area and penile enlargement. Three years after his initial presentation, whole exome sequencing for the diseases associated with elevated IgE revealed isolated heterozygous mutation for the R397Q mutation in the FOXP3 gene. Mother does not have the mutation and he has a brother with identical HLA typing for future bone marrow transplant.
IPEX presentation can be variable that this diagnosis should be considered in a male child with potential autoimmune neurological dysfunction if associated with immune deregulation and localized pruritic skin rashes.