A recurrent TP63 mutation causing EEC3 and Rapp–Hodgkin syndromes

Abstract

The ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3; OMIM #604292), the Rapp-Hodgkin syndrome (RHS), and various other syndromes are caused by mutations in the TP63 gene, which encodes a p53-like transcription factor. Here, we report on a woman aged 37 years and her daughter aged 3 years with the previously reported c.1028G>A (p.Arg343Gln) mutation in exon 8 of TP63. The mother lacked ectrodactyly, indicating a diagnosis of RHS, whereas the girl presented with all three major features (ectrodactyly, ectodermal dysplasia, clefting) and different minor features (including small and brittle nails, and recurrent conjunctivitis believed to be because of stenotic and blocked nasolacrimal ducts) of the EEC3 syndrome. The EEC and EEC-like syndromes are usually distinguished on the basis of the clinical findings; however, these syndromes show a huge variability in features because of variable expressivity and incomplete penetrance, making the correct clinical assignment difficult. In EEC3 syndrome and RHS, a clustering of mutations in the different domains of TP63 can be observed. Our findings indicate the clinical variability with TP63 mutations and underline that in the case of two syndromes being clinically possible in a patient, the final diagnosis should be assigned only after molecular diagnostics.

Case report: Prenatal diagnosis of Ectrodactyly–Ectodermal dysplasia–Cleft syndrome (EEC) in a fetus with cleft lip and polycystic kidney

“…Remarkable clinical variability has been observed for different TP63 mutations. Regarding the special amino acid mutation of R304 observed in the present case, we summarized the clinical presentations of the reported 33 cases with EEC syndrome and the R304 mutation ( Table 1 ) ( Wessagowit et al, 2000 ; van Bokhoven et al, 2001 ; Hamada et al, 2002 ; de Mollerat et al, 2003 ; Dianzani et al, 2003 ; Paranaíba et al, 2010 ; Gawrych et al, 2013 ; Okamura et al, 2013 ; Brueggemann and Bartsch, 2016 ; Wenger et al, 2018 ). Orofacial cleft, the most significant feature of EEC syndrome, is presented in approximately 80% of patients.…”

Adalimumab Experience in the Management of Hidradenitis Suppurativa Burdened with Rapp-Hodgkin Syndrome

“…[2]. Синдром характеризуется гипоплазией потовых желез, приводящей к гипо-, реже -ангидрозу (отсутствию потоотделения), наличием расщелины губы и неба, а также грубых и жестких волос, маленького рта, узкого носа, олигодонтии или анодонтии, конических зубов, анонихии, гипонихии, дистрофичных ногтей, аномалий протоков слезных желез, уха и слухового прохода, мочеполовой системы, молочных желез [3,4]. Синдром Рэппа -Ходжкина вызван изменениями в гене TP63, кодирующем опухолевый белок p63 [5].…”