Alternative titles; symbols
ORPHA: 99798; DO: 0050591;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xq13.1 | Tooth agenesis, selective, X-linked 1 | 313500 | X-linked dominant | 3 | EDA | 300451 |
A number sign (#) is used with this entry because of evidence that X-linked selective tooth agenesis-1 (STHAGX1) is caused by mutation in the gene encoding ectodysplasin A (EDA; 300451) on chromosome Xq13.
Mutations in the same gene can cause hypohidrotic ectodermal dysplasia (305100).
For a discussion of genetic heterogeneity of selective tooth agenesis, see 106600.
Erpenstein and Pfeiffer (1967) described transmission of oligodontia or hypodontia through 4 generations of a family. Males had oligodontia; females had hypodontia. No male-to-male transmission was observed. However, only 2 affected males had children (4 unaffected sons, 1 daughter with hypodontia). X-linked inheritance seemed likely.
In at least 18 persons in 4 generations Dahlberg (1937) noted absence of at least 6 anterior teeth in both dentitions. He suggested X-linked dominant inheritance, but against this was 1 unaffected daughter of the 1 affected male with children in the kindred.
Tao et al. (2006) reported a Mongolian family in which several members had congenital absence of teeth inherited in an X-linked recessive pattern. No member of the family had any other feature of hypohidrotic ectodermal dysplasia. The manifestation of hypodontia was not uniform in the family, indicating incomplete penetrance or variable expressivity. Affected members commonly had 2 pairs of permanent first molars. All of those affected had congenital absence of lower incisors and lower lateral incisors.
Tarpey et al. (2007) reported an Indian family in which almost all affected males had absence of all mandibular incisors and maxillary lateral incisors in both the primary and permanent dentition, with maxillary central incisors also missing in some cases. The absence of at least 1 incisor, typically of the maxillary lateral incisors, was also observed in affected females; at least 1 female had as severe a dental phenotype as the affected males. Inheritance was consistent with an X-linked dominant mechanism. No individuals reported abnormal sweating or heat intolerance. Tarpey et al. (2007) noted that the hypodontia in the family reported by Tao et al. (2006) was more severe and involved all classes of teeth.
In a family segregating X-linked congenital hypodontia, Tao et al. (2006) found linkage of the disorder with marker loci DXS1111, DXS1689, and DXS8101 (maximum 2-point lod score of 3.55). Haplotype analysis confined the locus to a less than 6.48-cM interval between DXS1124 and DXS1213 at Xq12-q13.1.
In a family segregating X-linked congenital hypodontia, Tao et al. (2006) identified a missense mutation in the EDA gene (R65G; 300451.0014) in all affected males and carrier females. Three of the 9 female carriers (33%) had a skewed X-chromosome inactivation pattern.
In affected members of an Indian family with X-linked incisor hypodontia, Tarpey et al. (2007) identified a mutation in the EDA gene (Q358E; 300451.0015).
In 4 affected males and 1 affected female carrier from a Chinese family with congenital hypodontia, Han et al. (2008) identified a mutation in the EDA gene (T338M; 300451.0018). The 7-year-old male proband had several deciduous teeth missing, but the shape of the residual teeth was normal. All 16 of the participating family members reported normal levels of sweating and of lachrymal and salivary secretions. Facial features, skin, hair, and nails appeared normal, and none had malformed teeth.
In 15 unrelated Chinese men with selective tooth agenesis, Song et al. (2009) sequenced the EDA gene and identified 4 patients with missense mutations: A259E (300451.0020) in 2 of the patients, and R289C (300451.0021) and R334H (300451.0022) in 1 each. The authors observed that all 4 patients had extensively distributed missing teeth in both upper and lower dentitions, including central and/or lateral incisors, but the shape and size of residual teeth were normal. Hair, skin, and nails were normal, and the patients reported normal sweating with no history of dry mouth, heat intolerance, or susceptibility to respiratory tract infections.
Han et al. (2008) analyzed 24 patients with defined mutations in the EDA gene and known patterns of tooth agenesis in their permanent dentition. Teeth with the highest probability of absence were the maxillary and mandibular lateral incisors (92%) and the mandibular central incisors (83%). Comparative analysis of the pattern of tooth agenesis between patients with EDA mutations and patients with hypodontia or tooth agenesis due to mutations in the MSX1 (142983) or PAX9 (167416) genes revealed several statistically significant differences (p less than 0.001): patients with EDA mutations were more likely to be missing maxillary and mandibular central incisors, lateral incisors, and canines, but maxillary and mandibular first permanent molars were more likely to be present.
Dahlberg, A. A. Inherited congenital absence of six incisors, deciduous and permanent. J. Dent. Res. 16: 59-62, 1937.
Erpenstein, H., Pfeiffer, R. A. Geschlechsgebunden-dominant erbliche Zahnunterzahl. Humangenetik 4: 280-293, 1967. [PubMed: 6080810] [Full Text: https://doi.org/10.1007/BF00292201]
Han, D., Gong, Y., Wu, H., Zhang, X., Yan, M., Wang, X., Qu, H., Feng, H., Song, S. Novel EDA mutation resulting in X-linked non-syndromic hypodontia and the pattern of EDA-associated isolated tooth agenesis. Europ. J. Med. Genet. 51: 536-546, 2008. [PubMed: 18657636] [Full Text: https://doi.org/10.1016/j.ejmg.2008.06.002]
Song, S., Han, D., Qu, H., Gong, Y., Wu, H., Zhang, X., Zhong, N., Feng, H. EDA gene mutations underlie non-syndromic oligodontia. J. Dent. Res. 88: 126-131, 2009. [PubMed: 19278982] [Full Text: https://doi.org/10.1177/0022034508328627]
Tao, R., Jin, B., Guo, S. Z., Qing, W., Feng, G. Y., Brooks, D. G., Liu, L., Xu, J., Li, T., Yan, Y., He, L. A novel missense mutation of the EDA gene in a Mongolian family with congenital hypodontia. J. Hum. Genet. 51: 498-502, 2006. [PubMed: 16583127] [Full Text: https://doi.org/10.1007/s10038-006-0389-2]
Tarpey, P., Pemberton, T. J., Stockton, D. W., Das, P., Ninis, V., Edkins, S., Futreal, P. A., Wooster, R., Kamath, S., Nayak, R., Stratton, M. R., Patel, P. I. A novel gln358glu mutation in ectodysplasin A associated with X-linked dominant incisor hypodontia. Am. J. Med. Genet. 143A: 390-394, 2007. [PubMed: 17256800] [Full Text: https://doi.org/10.1002/ajmg.a.31567]