Alternative titles; symbols
SNOMEDCT: 403762003; ORPHA: 2721;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q35 | Ectodermal dysplasia 16 (odontoonychodermal dysplasia) | 257980 | Autosomal recessive | 3 | WNT10A | 606268 |
A number sign (#) is used with this entry because of evidence that odontoonychodermal dysplasia (OODD) is caused by homozygous or compound heterozygous mutation in the WNT10A gene (606268) on chromosome on chromosome 2q35.
Odontoonychodermal dysplasia (OODD) is an autosomal recessive disorder characterized by dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, hyperkeratosis of the palms and soles, hypo- and hyperhidrosis of the skin, and atrophic patches on the face (summary by Adaimy et al., 2007; Yu et al., 2019).
In 3 consanguineous Lebanese Muslim Shiite sibships, Fadhil et al. (1983) described an apparently 'new' form of ectodermal dysplasia with dystrophic nails, misshapen teeth, including peg-shaped incisors, and erythematous lesions of face and thickening of the palms and soles which showed hyperhidrosis. The hair was unaffected in some but was described as dry and sparse with thinning of the eyebrows in others. The 3 sibships contained 24 children of whom 7 were affected.
Arnold et al. (1995) described a sporadic case. The 31-year-old man was born of nonconsanguineous parents. He complained of progressive thickening of the palmar skin with painful chaffing and increased sweating. Hypodontia with persistence of deciduous teeth was found. There was mild mental deficiency.
Zirbel et al. (1995) described an 11-month-old male infant of nonconsanguineous parents who had atrophic malar plaques that reddened with heat, nail dystrophy, sparse hair, lingual concavity of the incisors, a bifid maxillary incisor, a 5-cusped molar, and hyperhidrosis of the palms and soles. In addition, he had chronic tearing, photophobia, blepharitis, and a mild keratitis. Zirbel et al. (1995) concluded that the child most resembled patients with odontoonychodermal dysplasia, although his eye findings were unique.
Megarbane et al. (2004) reported 3 patients, 2 Lebanese Muslim Shiite brothers and their maternal cousin, who presented with dry hair, pilar keratosis, severe hypodontia, smooth tongue, onychodysplasia, and keratoderma and hyperhidrosis of palms and soles. Molecular analysis excluded X-linkage, suggesting instead autosomal recessive inheritance. The parents denied direct consanguinity but all members of the family originated from the same village.
Bohring et al. (2009) reported 12 patients from 11 unrelated families of German and Turkish origin with ectodermal dysplasia due to confirmed WNT10A mutations. A brother and sister from 1 family had oligodontia and sparse body hair and eyebrows as their only manifestations, and a female proband from another family had cysts of the eyelids in addition to hypodontia, hypotrichosis, palmoplantar keratosis, and dystrophic nails (Schopf-Schulz-Passarge syndrome; 224750). Three patients had photophobia, which was previously described in a patient with OODD by Zirbel et al. (1995). The proband with SSPS was also diagnosed with a porocarcinoma of the left heel. Bohring et al. (2009) suggested that patients with OODD might also be at increased risk for skin tumors. The most consistent finding in all cases and the most specific diagnostic criterion was severe oligodontia of the permanent teeth with normal or less-affected deciduous dentition, involving conical front teeth or agenesis of the upper lateral or central incisors. The authors noted that this pattern of tooth anomalies was similar to that seen in selective tooth agenesis-4 (STHAG4; 150400) and anodontia of permanent teeth (206780), dominant and recessive dental traits, respectively. Despite the high degree of variability in phenotypic expression, Bohring et al. (2009) stated that there was no recognizable genotype/phenotype correlation.
Yu et al. (2019) described 4 unrelated individuals with OODD. Findings in their deciduous teeth included microdontia, attrition, taurodontism, peg-shaped teeth, enamel hypoplasia, and missing teeth. All 4 patients had complete absence of permanent dentition and dystrophic nails. Three patients had palmoplantar hyperkeratosis, 2 had hypohidrosis, 1 had sparse scalp hair, and 2 had sparse eyebrows. One patient had atrophic and erythematous patches of skin on his face.
Adaimy et al. (2007) studied 3 consanguineous Lebanese Muslim Shiite families that included 6 individuals affected with odontoonychodermal dysplasia. Using a homozygosity mapping strategy, they assigned the disease locus to a region of approximately 9 cM at 2q35-q36.2, with a maximum multipoint lod score of 5.7.
The transmission pattern of OODD in the families reported by Adaimy et al. (2007) was consistent with autosomal recessive inheritance.
In affected members of 3 consanguineous Lebanese Muslim Shiite families with odontoonychodermal dysplasia, Adaimy et al. (2007) found homozygosity for the same nonsense mutation in the WNT10A gene (E233X; 606268.0001). The mutation was predicted to result in a prematurely terminated protein of 232 amino acids instead of 417 amino acids. One of the families had been reported by Megarbane et al. (2004), and another was a branch of one of the families described by Fadhil et al. (1983). The authors stated that this was the first report of a phenotype related to a mutation in WNT10A and the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, thus expanding the list of WNT-related diseases.
In 12 patients from 11 unrelated families of German and Turkish origin with ectodermal dysplasia, who were known to be negative for mutation in the ectodysplasin-A gene (EDA; 300451), Bohring et al. (2009) identified homozygosity or compound heterozygosity for 5 missense and nonsense mutations in the WNT10A gene (606268.0002-606268.0006). Approximately half of heterozygotes had minor manifestations, and none of the wildtype homozygotes had any symptoms.
In 2 Indian sibs with OODD, Xu et al. (2017) identified homozygosity for a splice site mutation in the WNT10A gene (606268.0010). Both parents were heterozygous for the mutation.
In 4 unrelated patients with OODD, Yu et al. (2019) identified 5 novel mutations in the WNT10A gene (see, e.g., 606268.0011-606268.0013). The mutations segregated with the disorder in the families for which parental DNA was available for testing.
Adaimy, L., Chouery, E., Megarbane, H., Mroueh, S., Delague, V., Nicolas, E., Belguith, H., de Mazancourt, P., Megarbane, A. Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. Am. J. Hum. Genet. 81: 821-828, 2007. [PubMed: 17847007] [Full Text: https://doi.org/10.1086/520064]
Arnold, W. P., Merkx, M. A. W., Steijlen, P. M. Variant of odontoonychodermal dysplasia? Am. J. Med. Genet. 59: 242-244, 1995. [PubMed: 8588594] [Full Text: https://doi.org/10.1002/ajmg.1320590224]
Bohring, A., Stamm, T., Spaich, C., Haase, C., Spree, K., Hehr, U., Hoffmann, M., Ledig, S., Sel, S., Wieacker, P., Ropke, A. WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes. Am. J. Hum. Genet. 85: 97-105, 2009. [PubMed: 19559398] [Full Text: https://doi.org/10.1016/j.ajhg.2009.06.001]
Fadhil, M., Ghabra, T. A., Deeb, M., Der Kaloustian, V. M. Odontoonychodermal dysplasia: a previously apparently undescribed ectodermal dysplasia. Am. J. Med. Genet. 14: 335-346, 1983. [PubMed: 6837628] [Full Text: https://doi.org/10.1002/ajmg.1320140213]
Megarbane, H., Haddad, M., Delague, V., Renoux, J., Boehm, N., Megarbane, A. Further delineation of the odonto-onycho-dermal dysplasia syndrome. Am. J. Med. Genet. 129A: 193-197, 2004. [PubMed: 15316967] [Full Text: https://doi.org/10.1002/ajmg.a.30188]
Xu, M., Horrell, J., Snitow, M., Cui, J., Gochnauer, H., Syrett, C. M., Kallish, S., Seykora, J. T., Liu, F., Gaillard, D., Katz, J. P., Kaestner, K. H., and 13 others. WNT10A mutation causes ectodermal dysplasia by impairing progenitor cell proliferation and KLF4-mediated differentiation. Nature Commun. 8: 15397, 2017. Note: Electronic Article. [PubMed: 28589954] [Full Text: https://doi.org/10.1038/ncomms15397]
Yu, M., Liu, Y., Liu, H., Wong, S.-W., He, H., Zhang, X., Wang, Y., Han, D., Feng, H. Distinct impacts of bi-allelic WNT10A mutations on the permanent and primary dentitions in odonto-onycho-dermal dysplasia. Am. J. Med. Genet. 179A: 57-64, 2019. [PubMed: 30569517] [Full Text: https://doi.org/10.1002/ajmg.a.60682]
Zirbel, G. M., Ruttum, M. S., Post, A. C., Esterly, N. B. Odonto-onycho-dermal dysplasia. Brit. J. Derm. 133: 797-800, 1995. [PubMed: 8555039] [Full Text: https://doi.org/10.1111/j.1365-2133.1995.tb02761.x]