Patients with mutations in the ectodysplasin receptor signalling pathway genes - the X-linked ligand ectodysplasin-A (<i>EDA</i>), the receptor <i>EDAR</i> or the receptor adapter <i>EDARADD</i> - have hypohidrotic ectodermal dysplasia (HED).
In total, four genes, namely ectodysplasin A (EDA), ectodysplasin A receptor (EDAR), EDAR-associated death domain protein (EDARADD) and Wnt family member 10A (WNT10A), are known to be involved in the etiology of HED.
Hypohidrotic ectodermal dysplasia (HED) is a rare hereditary disorder that affects tissues derived from the ectoderm including hair, teeth and sweat glands.EDA is the major causative gene of HED.
The aim of this review was to update the main clinical characteristics of HED regarding to recent molecular advances in the comprehension of all the possible genes involved in this group of disorders since it is known that Eda-A1-Edar signaling has multiple roles in ectodermal organ development, regulating their initiation, morphogenesis, and differentiation steps.
Therefore the aim of the study was to search for etiological variations of EDA and other candidate genes in two unrelated Egyptian male children with sporadic non-syndromic tooth agenesis (NTA) and hypohidrotic ectodermal dysplasia (HED).
Hypohidrotic ectodermal dysplasia (HED) results from mutation of the EDA, EDAR or EDARADD genes and is characterized by reduced or absent eccrine sweat glands, hair follicles and teeth, and defective formation of salivary, mammary and craniofacial glands.
Significant differences in the number of some primary missing teeth (incisor and canine) related to EDA-EDAR genes defects were detected for the first time between XLHED and autosomal recessive HED, suggesting differential local effects of EDA-EDAR genes during odontogenesis.
We also present a new mutation in the EDA gene which causes selective tooth agenesis and demonstrates the phenotype variation that can be encountered in the ectodermal dysplasia syndrome (HED) with the highest prevalence worldwide.