ANKYLOBLEPHARON ECTODERMAL DEFECTS WITH CLEFT LIP/PALATE SYNDROME AND T-CELL LYMPHOPENIA RESULTING FROM TP-63 MUTATION

Introduction Since the advent of routine newborn screening programs, neonates at risk for severe combined immunodeficiency (SCID) are often identified before onset of severe illness, which has significantly improved prognosis and outcomes. The differential diagnosis for SCID is broad. This case presents a rare instance of a female infant identified by abnormal newborn screen (NBS) with t-cell lymphopenia that is a result of TP63 mutation (OMIM 603273). Case Description The patient is a 3 week old female born at 36 5/7 weeks gestational age, identified by NBS as being at risk for SCID based on t-cell receptor excision circle (TREC) count below normal cutoff. Physical exam findings included diffuse epidermal erythema with areas of sloughed skin, ankyloblepharon and bilateral cleft lip/palate. Immunologic evaluation indicated moderate t-cell lymphopenia with slightly abnormal naive CD4+ t-cell count and reassuring mitogen stimulation assay. She was subsequently found to have a mutation in tumor suppressor gene TP63 . Her constellation of findings is consistent with ankyloblepharon ectodermal defects with cleft lip/palate (AEC) syndrome. Despite her t-cell lymphopenia, she remains healthy. Discussion The differential diagnosis for abnormal NBS concerning for SCID is broad, and uncommon etiologies such as TP63 mutation should remain on the differential, particularly when physical exam findings are concerning for syndromic diagnosis. The phenotype of patients with AEC and TP63 mutation is heterogeneous, and very few of these patients have had their immune system characterized. This currently unreported case further characterizes the variable immunophenotype of AEC syndrome and provides evidence of an association between TP63 mutations and AEC syndrome.