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Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip/Palate Syndrome with Concomitant Lymphopenia: A Novel TP63 Mutation
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Adeeb A. Bulkhi, MD, Tara V. Saco, M.D., Richard F. Lockey, MD FAAAAI, Mark C. Glaum, MD PhD FAAAAI
Rationale: Ectodermal dysplasia, ectrodactyly, and cleft lip/palate syndrome (EEC) is an autosomal dominant syndrome that affects ectodermal structures. Rarely, lymphopenia is present with normal thymic development.

Methods: Genetic sequencing was performed for lymphopenia in an EEC infant.

Results: A newborn female with cleft lip, imperforate anus, and polydactyly was born at 37 weeks to a 31 year-old American of African descent with ectodermal dysplasia. Physical exam also revealed abnormal external genitalia, right foot syndactyly, skin erythema and scaling, and abnormal hair growth of the scalp. There was no evidence of thymic or cardiac abnormalities on imaging. The T cell receptor excision circle (TREC) count, which was 14 (normal > 25 copies/uL) suggested SCID. The lymphocyte subset panel revealed low CD3, 4, 8 and 19, with normal NK cells. The lymphocyte proliferation assay with mitogens was normal. Immunoglobulin levels were appropriate for her age. A novel, presumably pathogenic de novo amino acid substitution in exon 9 of TP63 (c.1039T>C; p.Cys347Arg; NCBI Reference Sequence NM_033303.3) was identified.

Conclusions: A novel TP63 mutation in EEC is reported leading to T and B cell lymphopenia with normal thymic development. Lymphocyte proliferative response was normal despite an abnormal TREC count and lymphopenia.  However, case reports of EEC exist where lymphocyte proliferative response is abnormal. Therefore, the workup for EEC should include a TREC assay and if abnormal, pursue detailed evaluation for immunodeficiency.