Ankyloblepharon-ectodermal defect-cleft lip/palate (AEC) syndrome (Hay–Wells syndrome, MIM #106220) belongs to a large, heterogeneous group of ectodermal dysplasias (ED) that affect embryonic development of ectodermal tissues: hair, nails, teeth, sweat glands, and skin [McKusick, 1987]. The number and definition of distinct ED syndromes are ambiguous because of overlapping phenotypes and genotypes, and estimates of their overall incidence vary widely [Brunner et al., 2002].
Recent discoveries have linked AEC and several allelic disorders to mutations in TP63, a homologue of TP53 [McGrath et al., 2001]. These TP63 mutations give rise to a varied range of phenotypes in patients affected by AEC syndrome. TP63 is an important regulatory gene and appears to control processes related to epidermal proliferation and differentiation [Koster and Roop, 2004a].
The ground work for this conference was laid at the 2003 AEC Skin Erosion Workshop held in St. Louis, MO and sponsored by the National Foundation for Ectodermal Dysplasias (NFED), which provides support for ED families and advocates for clinical and basic science research. Participants at this workshop discussed directions for future research, formulated consensus recommendations for improved skin and wound care [Siegfried et al., 2005] and also recognized the need for more extensive clinical evaluation and tissue sampling to further the understanding of this disorder. Subsequently on November 8–10, 2006, the NFED convened the International Research Symposium on Ankyloblepharon-Ectodermal Defect-Cleft Lip/Palate (AEC) Syndrome in Houston, Texas. Participants included clinical professionals and biomedical researchers from North America and Europe and 23 affected individuals from 13 families. Reaching beyond the scope of the first conference, participants worked together to examine and systematically document the clinical findings of these patients to develop a uniform, coordinated approach to diagnosis. The results of these subspecialty evaluations are detailed in the subsequent manuscripts [see Bree, 2009; Cole et al., 2009; Dishop et al., 2009; Farrington and Lausten, 2009; Julapalli et al., 2009; Lane et al., 2009; Motil and Fete, 2009; Sutton et al., 2009 in this issue]. Blood, hair, and nail specimens were also obtained for mutational, microscopic, and immunohistochemical evaluation, with these results also presented [see Beaudry et al., 2009; Dishop et al., 2009; Koster et al., 2009; Rinne et al., 2009 this issue].
This unique research, educational, and patient-oriented symposium began with a day of structured clinical evaluations by multiple subspecialists (Appendix II) in the areas of audiology, dentistry [see Farrington and Lausten, 2009 this issue], dermatology [see Julapalli et al., 2009 this issue], genetics [see Sutton et al., 2009 this issue], growth/nutrition/gastroenterology [see Motil and Fete, 2009 this issue], otorhinolaryngology [see Cole et al., 2009 this issue], ophthalmology, plastic surgery, and psychiatry [see Lane et al., 2009 this issue] to obtain and document clinical history and physical examination findings prospectively. The patients also donated tissue samples, including blood, hair, and skin biopsies [see Beaudry et al., 2009; Dishop et al., 2009; Koster et al., 2009; Rinne et al., 2009 this issue]. On the second day, the patients participated in a Grand Rounds conference. The Baylor Dermatology Residents (Appendix III) presented the case studies to the group for discussion, followed by participant lectures on AEC-related topics: medical history, nosology, genetics, as well as TP63-associated developmental and molecular biological research. On the third day, the faculty participated in a round table discussion focused on defining better diagnostic markers, current care guidelines, and improved coordination between the clinical and research communities. The overarching goal was to establish a long-term direction for AEC research.