International Research Symposium on Ankyloblepharon‐Ectodermal Defects‐Cleft Lip/Palate (AEC) Syndrome

Abstract

Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) Syndrome (Hay-Wells syndrome, MIM #106220) is a rare autosomal dominant ectodermal dysplasia syndrome. It is due to mutations in the p63 gene, known to be a regulatory gene with many downstream gene targets. TP63 is important in the differentiation and proliferation of the epidermis, as well as many other processes including limb and facial development. It is also known that mutations in p63 lead to skin erosions. These erosions, especially on the scalp, are defining features of AEC syndrome and cause significant morbidity and mortality in these patients. It was this fact that led to the 2003 AEC Skin Erosion Workshop. That conference laid the groundwork for the International Research Symposium for AEC Syndrome held at Texas Children's Hospital in 2006. The conference brought together the largest cohort of individuals with AEC syndrome, along with a multitude of physicians and scientists. The overarching goals were to define the clinical and pathologic findings for improved diagnostic criteria, to obtain tissue samples for further study and to define future research directions. The symposium was successful in accomplishing these aims as detailed in this conference report. Following our report, we also present eleven manuscripts within this special section that outline the collective clinical, pathologic and mutational data from eighteen individuals enrolled in the concurrent Baylor College of Medicine IRB-approved protocol: Characterization of AEC syndrome. These collaborative findings will hopefully provide a stepping stone to future translational projects of p63 and p63-related syndromes.

Integrating Animal Models and In Vitro Tissue Models to Elucidate the Role of Desmosomal Proteins in Diseases

“…This is caused, in part, by the lack of availability of skin samples for this rare disorder. We obtained skin biopsies from AEC patients, thus allowing us to interrogate abnormal expression of genes and proteins associated with skin integrity (Fete et al, 2009; Koster et al, 2009; Beaudry et al, 2009). Consistent with reports using smaller sample sets, our analysis of AEC patient skin revealed the presence of suprabasal proliferation, impaired terminal differentiation, and abnormal deposition of basement membrane components (Koster et al, 2009; Marinari et al, 2009; Clements et al, 2012; Browne et al, 2011; McGrath et al, 2001).…”

P63‐related disorders: Dermatological characteristics in 22 patients

“…They are mainly located on the scalp and may extend to the neck, shoulders, back and buttocks. Palms and soles might be involved (18% in our series) . Complete wound healing varies from 2 months to 12 years.…”

“…Complete wound healing varies from 2 months to 12 years. Persistent and/or recurrent erosions on the scalp impact the daily life and might interfere with the laying of the hearing aid . The pathophysiological mechanisms of erosions and their healing remain unknown.…”

Anatomical analysis of zygomatic bone in ectodermal dysplasia patients with oligodontia

“…Some authors suggested that the dysregulation of the EDA‐NF‐κB signaling pathway resulted in abnormal skeletogenic neural crest cell differentiation, migration, and osteoclastic differentiation such that craniofacial abnormalities presented clinical signs in ED patients . Mutation of the p 63 gene also caused disorders in facial development because the transcription and expression of the p 63 gene played an essential role in epidermal differentiation and proliferation during embryogenesis . Additionally, other authors suggested that craniofacial features, such as reduced maxilla length and prognathism, retroclined nasal bone, short nose, and reduced facial height, also resulted from the absence of teeth .…”