Alternative titles; symbols
ORPHA: 1810, 238468; DO: 0111653;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q42.3-q43 | Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant | 614940 | Autosomal dominant | 3 | EDARADD | 606603 |
A number sign (#) is used with this entry because autosomal dominant ectodermal dysplasia-11A (ECTD11A) is caused by heterozygous mutation in the EDAR (604095)-associated death domain gene (EDARADD; 606603) on chromosome 1q42-q43.
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings.
Hypohidrotic, or anhidrotic, ectodermal dysplasia (HED/EDA) is characterized by a triad of signs comprising sparse hair (hypotrichosis), abnormal or missing teeth (anodontia or hypodontia), and inability to sweat (anhidrosis or hypohidrosis). Typical clinical manifestations also include dryness of the skin, eyes, airways, and mucous membranes presumably due to the defective development of several exocrine glands. Hypohidrotic ectodermal dysplasia can be associated with dysmorphic features (forehead bumps, rings under the eyes, everted nose, and prominent lips) and occasionally with absent nipples (summary by Cluzeau et al., 2011).
Bal et al. (2007) reported a large Moroccan family in which 7 members had the clinical triad of hypohidrotic ectodermal dysplasia, i.e., hypotrichosis, hypodontia, and anhidrosis.
Wohlfart et al. (2016) described a German family in which a 16-year-old girl, her mother, and her maternal grandfather all had very thin, brittle, sparse or even absent hair and reduced sweating. Dental x-rays of the proband confirmed absence of a considerable number of permanent teeth, and her mother and grandfather also had a reduced number of permanent teeth. The proband had bilateral amazia and her mother had unilateral amazia. In addition, the girl developed bilateral mature ovarian teratomas containing hair, sebaceous glands, and sweat glands.
The transmission pattern of HED in the family reported by Bal et al. (2007) was consistent with autosomal dominant inheritance.
In a Moroccan family segregating autosomal dominant HED, Bal et al. (2007) demonstrated that the disorder mapped to a 5-cM region of chromosome 1q42-q43 encompassing the EDARADD gene.
In 7 affected members of a large Moroccan family with autosomal dominant anhidrotic ectodermal dysplasia, who were negative for mutation in the EDAR gene, Bal et al. (2007) identified a heterozygous mutation in the EDARADD gene (606603.0002). The findings indicated that mutations in the EDARADD gene can cause autosomal dominant and autosomal recessive HED (see 614941).
In a male patient with oligodontia, Bergendal et al. (2011) identified a heterozygous missense mutation in the EDARADD gene that was predicted to be functionally relevant. The patient, who was not clinically ascertained, did not report any ectodermal symptoms besides the teeth.
In a 3-generation German family with HED, Wohlfart et al. (2016) identified heterozygosity for a missense mutation in the EDARADD gene (D123N; 606603.0003) that segregated fully with disease and was not found in the ExAC database.
Bal, E., Baala, L., Cluzeau, C., El Kerch, F., Ouldim, K., Hadj-Rabia, S., Bodemer, C., Munnich, A., Courtois, G., Sefiani, A., Smahi, A. Autosomal dominant anhidrotic ectodermal dysplasias at the EDARADD locus. Hum. Mutat. 28: 703-709, 2007. [PubMed: 17354266] [Full Text: https://doi.org/10.1002/humu.20500]
Bergendal, B., Klar, J., Stecksen-Blicks, C., Norderyd, J., Dahl, N. Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes. Am. J. Med. Genet. 155A: 1616-1622, 2011. [PubMed: 21626677] [Full Text: https://doi.org/10.1002/ajmg.a.34045]
Cluzeau, C., Hadj-Rabia, S., Jambou, M., Mansour, S., Guigue, P., Masmoudi, S., Bal, E., Chassaing, N., Vincent, M.-C., Viot, G., Clauss, F., Maniere, M.-C., and 11 others. Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases. Hum. Mutat. 32: 70-77, 2011. [PubMed: 20979233] [Full Text: https://doi.org/10.1002/humu.21384]
Wohlfart, S., Soder, S., Smahi, A., Schneider, H. A novel missense mutation in the gene EDARADD associated with an unusual phenotype of hypohidrotic ectodermal dysplasia. Am. J. Med. Genet. 170A: 249-253, 2016. [PubMed: 26440664] [Full Text: https://doi.org/10.1002/ajmg.a.37412]