ORPHA: 75392; DO: 0080987;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12p13.31 | Ehlers-Danlos syndrome, periodontal type, 2 | 617174 | Autosomal dominant | 3 | C1S | 120580 |
A number sign (#) is used with this entry because of evidence that Ehlers-Danlos syndrome periodontal type 2 (EDSPD2) is caused by heterozygous mutation in the C1S gene (120580) on chromosome 12p13.
Periodontal Ehlers-Danlos syndrome type 2 (EDSPD2) is an autosomal dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings (Kapferer-Seebacher et al., 2016).
For a general phenotypic description and discussion of genetic heterogeneity of EDSPD, see EDSPD1 (130080).
Kapferer-Seebacher et al. (2016) studied 2 families with Ehlers-Danlos syndrome and periodontitis. In the first family (family 16), the 45-year-old female proband exhibited mild elastic skin, easy bruising, fragile skin with pretibial discoloration, and early-onset periodontitis resulting in tooth loss in her teens. Her father, 1 sister and 1 brother, and 2 of her sons had a similar phenotype. Other features in the proband and her affected sister included significant spinal osteoarthritis, fragile skin on the fingers and legs, irritable bowel symptoms, and flu-like symptoms without fever. Three of the affected individuals were diagnosed with cancer, including Wilms tumor. In the second family (family 17), the proband was a 75-year-old man with features of periodontal EDS including thin, fragile, and hyperelastic skin, easy bruising, atrophic scars, pretibial discoloration, and scoliosis. He developed periodontitis in his 20s and had lost 20 teeth by age 60. Eight of 9 affected relatives also had early-onset periodontitis, gingival recession, early tooth loss, and pretibial discoloration. In addition, 4 affected relatives had cancer, including of the uterus, breast, and colon, and lymphocytic lymphoma of the lung.
The transmission pattern of EDSPD2 in the families studied by Kapferer-Seebacher et al. (2016) was consistent with autosomal dominant inheritance.
In affected members of 2 unrelated families (families 16 and 17) with EDSPD2, Kapferer-Seebacher et al. (2016) identified heterozygous mutations in the C1S gene (120580.0003 and 120580.0004).
Kapferer-Seebacher, I., Pepin, M., Werner, R., Aitman, T. J., Nordgren, A., Stoiber, H., Thielens, N., Gaboriaud, C., Amberger, A., Schossig, A., Gruber, R., Giunta, C., and 28 others. Periodontal Ehlers-Danlos syndrome is caused by mutations in C1R and C1S, which encode subcomponents C1r and C1s of complement. Am. J. Hum. Genet. 99: 1005-1014, 2016. [PubMed: 27745832] [Full Text: https://doi.org/10.1016/j.ajhg.2016.08.019]