A Family with EEC Syndrome in the Son and ADULT Syndrome in His Father Caused by the c.797G>A (p.Arg266Gln) Pathogenic Variant in the TP63 Gene

Abstract

Introduction: To our knowledge, there are few examples of intrafamilial variability involving two different TP63-linked morphopathies within a same family. Here, we describe a Mexican family in which the son had ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3), and his father acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome, both heterozygous for the p.Arg266Gln pathogenic variant in TP63. Additionally, we reviewed the clinical information reported for this TP63 genotype.

Case presentation: The son of this family presented ectodermal defects (thin and sparse hair, mild nail dysplasia), tetramelic ectrodactyly, syndactyly, and nasolacrimal duct obstruction (NLDO), indicative of an EEC3 diagnosis. His father, however, exhibited severe NLDO, facial freckling, dental abnormalities, mild nail dysplasia, and a history of micturition problems, compatible with ADULT syndrome. Both were heterozygous for the NM_003722.5(TP63):c.797G>A (p.Arg266Gln) pathogenic variant in TP63.

Discussion: This report expands the spectrum of intrafamilial variability confirming that this can include the expression of distinct types of TP63-related disorders among different members of the same family, whose implications should be also considered in genetic counseling. From our review, we observed that p.Arg266Gln variant seems to correlate particularly with the presence of NLDO, sparse hair/eyebrows, ridged/dystrophic nails, anodontia/hypodontia, and micturition difficulties, as well as for a minor frequency of cleft lip/cleft palate.

Keywords: Ectrodactyly; Freckling; Intrafamilial variability; Micturition problems; Nasolacrimal duct obstruction; TP63.