Mutations in P63 and IRF-6 Present with Overlapping Craniofacial Defects: A study from Lebanon

Mazen Kurban,Lamiaa Hamie,Pamela Kassabian,Edgar Jabbour

doi:10.31487/j.ord.2019.01.04

Abstract

Interferon Regulatory Factor 6 (IRF-6) and p63 are two vital transcription factors implicated in normal craniofacial development. In this report, we present a family with Van Der Woude Syndrome (VWS) with a mutation in exon 9 of IRF-6 gene and a phenotypically overlapping case of Rapp-Hodgkin Syndrome (RHS) resulting from a mutation in the p63 gene. Members from both families presented with congenital lip pits and cleft lip/palate. The RHS case had additional ectodermal features that underscore the upstream nature of p63 in the complex p63-IRF-6 interactive pathway.

Highlights

The intricate nature of embryogenesis requires tightly regulated interactions between different signaling pathways
We present a family with Van Der Woude Syndrome (VWS) with a mutation in exon 9 of Interferon Regulatory Factor 6 (IRF-6) gene and a phenotypically overlapping case of Rapp-Hodgkin Syndrome (RHS) resulting from a mutation in the p63 gene
P63 is a key protein and its loss or aberrant functioning is often the major culprit in ectodermal dysplasias, those presenting with cleft lip and palate (CLP)

Summary

Introduction

The intricate nature of embryogenesis requires tightly regulated interactions between different signaling pathways. P63-related disorders are divided into six major groups, each is categorized by a constellation of phenotypic features and deleterious heterozygous mutations in p63 These six groups are at times hard to clinically differentiate as many features are overlapping, in addition there is a wide range of intra-syndromic, and intra-familial variability [1]. CLP are cardinal features of Ectrodactyly-EctodermalDysplasia-Cleft-lip/palate (EEC) Syndrome, AnkyloblepharonEctodermal dysplasia-clefting (AEC) syndrome, and Rapp-Hodgkin Syndrome (a milder form of AEC), all of which are P63-related disorders. This highlights the importance of P63 in craniofacial development [1]. There are two IRF-6- related syndromes; Van der Woude (VWS) and popliteal pterygium syndromes (PPS) These are autosomal dominant disorders categorized by the presence of lower lip pits [2]. The clinical and molecular data underscores the cross-talk/interaction between p63 and IRF-6 in craniofacial development

Family 1

Findings

Discussion