The term ectodermal dysplasia (ED) has been used to describe around 200 different clinical conditions . EDs are genetic disorders with lack or dysgenesis of at least two of the ectodermal derivatives hair, nails, teeth or sweat glands . Hypohidrotic ectodermal dysplasia (HED) is the most common form of ectodermal dysplasia and is characterized by defective development of teeth, hair, and sweat glands. Common symptoms in subjects with HED are reduced number of teeth and sweat glands, reduced saliva secretion, sparse and thin hair, and dry skin . Other clinical manifestations are dryness of airways and mucous membranes presumably due to the defective development of exocrine glands. HED can also be associated with dysmorphic facial features as a prominent forehead, dark, hyperkeratinized skin around the eyes, everted nose, and prominent lips .
HED can be inherited in an X-linked, autosomal dominant or autosomal recessive manner . Four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases .
The EDAR protein plays an important role for embryogenesis. The protein is a member of the tumor necrosis factor (TNF) receptor family, and is activated by its ligand EDA and uses EDARADD as an adaptor to build an intracellular NF-kB signal-transducing complex which is necessary for normal development of ectodermal organs both in humans and in mice [5, 6], Autosomal dominant (AD) forms of HED have previously been linked to mutations in the ectodysplasin 1 anhidrotic receptor (EDAR) protein but mutations in the EDAR gene are also associated with recessive forms of ED [7, 8]. Mutations in EDAR have been reported to account for 25 per cent of non-EDA1 HED cases .
Previously we analyzed the coding sequence of the EDAR gene in two families with AD HED and in both families identified a non-sense C to T mutation in exon 12, c.1072C > T, that changes an arginine amino acid into a stop codon; p. Arg358X . Our finding corroborated an earlier finding in an American family . AD HED is not as thoroughly clinically characterized as the more common X-linked HED, although one clinical study in a family with putative AD HED was made in Texas, USA, where affected members of the family had mild hypotrichosis, mild hypodontia and variable degrees of hypohidrosis . Another large American family with known AD HED showed hypotrichosis, hypohidrosis, hypodontia with abnormally shaped teeth, and variable nail abnormalities , however, in this study number and type of missing teeth was not reported. Additionally, three successive generations of women with AD HED with a defect of the 2q12 region has been described with alopecia, anhidrosis, hypodontia and malar hypoplasia .
The aim of the present study was to clinically describe individuals with the c.1072C > T mutation (p. Arg358X) in the EDAR gene with respect to dental signs and saliva secretion, symptoms from other ectodermal structures and to assess orofacial function. A secondary aim was to assess caries experience and dental treatment received and to compare all outcomes with family members without the mutation. The null hypothesis was that there were no differences between family members with and without the c.1072C > T mutation.