Home / Deep Research / Odonto-Onycho-Dermal Dysplasia

Odonto-Onycho-Dermal Dysplasia

1. Disease Information

2026-04-24
Falcon MONDO:0009773 Model: Edison Scientific Literature 22 citations

1. Disease Information

1.1 Definition and overview

OODD is described in the original gene-discovery paper as “a rare autosomal recessive syndrome” with dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma, and hyperhidrosis of palms and soles. (adaimy2007mutationinwnt10a pages 1-4)

Bohring et al. similarly summarize OODD (MIM 257980) as an autosomal recessive ectodermal dysplasia with severe oligodontia, nail dystrophy, hypotrichosis, smooth tongue with reduced papillae, and palmoplantar hyperkeratosis with altered sweating. (bohring2009wnt10amutationsare pages 1-3)

1.2 Key identifiers (as available in retrieved sources)

Note: Orphanet, ICD-10/ICD-11, and MeSH identifiers were not explicitly present in the retrieved excerpts and therefore cannot be reliably asserted from this evidence set.

1.3 Synonyms / alternative names

The retrieved primary OODD papers mainly use “odonto-onycho-dermal dysplasia (OODD)” and situate it within a broader WNT10A phenotypic spectrum that overlaps with other ectodermal dysplasias (including Schöpf–Schulz–Passarge syndrome). (bohring2009wnt10amutationsare pages 1-3, tardieu2017dentalandextra‐oral pages 1-3)

1.4 Evidence source type

The disease description and genotype–phenotype relationships in this report are derived from: - Human primary clinical genetics (affected families, case series, multicenter cohorts, case reports) (adaimy2007mutationinwnt10a pages 1-4, bohring2009wnt10amutationsare pages 1-3, tardieu2017dentalandextra‐oral pages 10-13) - Model organism evidence (mouse Wnt10a knockout and Wnt10a/Wnt10b double mutants) (tardieu2017dentalandextra‐oral pages 10-13, yoshinaga2023effectsofwnt10a pages 2-4)

2. Etiology

2.1 Disease causal factors

OODD is caused by biallelic pathogenic variants in WNT10A, consistent with autosomal recessive inheritance. (adaimy2007mutationinwnt10a pages 1-4, bohring2009wnt10amutationsare pages 1-3, yu2019distinctimpactsof pages 1-2)

  • In the initial linkage and sequencing study, all affected individuals from three consanguineous families carried the same homozygous nonsense variant c.697G>T (p.Glu233X) in exon 3 of WNT10A, predicted to truncate the protein (232 aa vs 417 aa). (adaimy2007mutationinwnt10a pages 4-6)

2.2 Genetic risk factors and genotype–phenotype considerations

  • Biallelic WNT10A variants are associated with syndromic ectodermal dysplasia phenotypes including OODD, and can produce very severe permanent tooth agenesis, including anodontia of permanent teeth. (yu2019distinctimpactsof pages 1-2)
  • Heterozygous WNT10A variants can be associated with milder ectodermal findings or isolated dental anomalies; in one ED cohort, about half of heterozygotes (53.8%) showed phenotypic manifestations, with sex-biased expression. (bohring2009wnt10amutationsare pages 1-3)

2.3 Protective factors

No genetic or environmental protective factors were identified in the retrieved evidence specific to OODD.

2.4 Gene–gene (modifier) interactions and recent developments (2023–2024 prioritized)

Recent case-based evidence suggests modifier/digenic effects influencing severity: - 2023 (Children): a patient with prominent dental phenotype and mild ectodermal signs carried compound heterozygous WNT10A variants (c.310C>T; p.Arg104Cys and c.742C>T; p.Arg248Ter) and was homozygous for an EDAR polymorphism (c.1109T>C; p.Val370Ala). The authors state the EDAR370A allele “might also attenuate the severity of other ED signs.” (garciamartinez2023dentalphenotypewith pages 1-2) - 2024 (BMC Oral Health): in two brothers with HED due to an EDA variant (c.878T>G), the more severe tooth agenesis phenotype occurred in the sibling with additional compound heterozygous WNT10A missense variants, and the authors conclude: “Compound heterozygous WNT10A missense variations may exacerbate the number of missing teeth in HED caused by EDA variation.” (liu2024compoundheterozygouswnt10a pages 1-2)

3. Phenotypes

3.1 Core phenotype spectrum (current understanding)

Across primary reports, OODD involves ectoderm-derived tissues: - Dental: severe hypodontia/oligodontia/tooth agenesis; peg-shaped/conical teeth; enamel hypoplasia; retained primary teeth; and other dental morphology anomalies. (adaimy2007mutationinwnt10a pages 1-4, yu2019distinctimpactsof pages 1-2, yu2019distinctimpactsof pages 2-3) - Nails: dystrophy/onych(o)dysplasia. (yu2019distinctimpactsof pages 2-3, bohring2009wnt10amutationsare pages 1-3) - Hair: sparse/dry/thin hair, hypotrichosis. (adaimy2007mutationinwnt10a pages 1-4, yu2019distinctimpactsof pages 1-2) - Skin/palms/soles: palmoplantar keratoderma/hyperkeratosis; xerosis; sometimes erythematous/atrophic facial patches. (bohring2009wnt10amutationsare pages 1-3, yu2019distinctimpactsof pages 1-2) - Sweating: hypo- and/or hyperhidrosis. (bohring2009wnt10amutationsare pages 3-5, yu2019distinctimpactsof pages 2-3) - Tongue: smooth tongue due to reduced papillae. (adaimy2007mutationinwnt10a pages 1-4, bohring2009wnt10amutationsare pages 3-5)

3.2 Phenotype frequencies / statistics from available cohorts

  • In a 4-patient OODD case series with bi-allelic WNT10A variants, peg-shaped teeth, microdontia, severe attrition, and dystrophic nails were present in 4/4, while palmar/plantar hyperkeratosis occurred in 3/4 and hypohidrosis in 2/4. (yu2019distinctimpactsof pages 2-3)
  • In a multicenter cohort of 41 patients with WNT10A mutations, major skeletal/cartilaginous anomalies were observed in 4 patients (~10%). (tardieu2017dentalandextra‐oral pages 10-13)

3.3 Onset and progression

3.4 Quality of life impacts (as available)

Formal QoL instruments were not identified in the retrieved excerpts. However, cohort descriptions report functional burdens including painful palmoplantar lacerations and discomfort at warm temperatures, consistent with keratoderma and sweating dysfunction. (bohring2009wnt10amutationsare pages 3-5)

3.5 Suggested HPO mapping

A curated HPO mapping table is provided below.

Table (click to expand)
Domain Clinical feature Suggested HPO term(s) Evidence/frequency Notes
Dentition Oligodontia / severe tooth agenesis HP:0000677 Oligodontia; HP:0009804 Tooth agenesis Core OODD feature across reports; in a 41-patient WNT10A cohort, mild-to-severe oligodontia was observed in all patients with biallelic WNT10A variants; WNT10A variants are common in selective tooth agenesis (35–50%) (tardieu2017dentalandextra‐oral pages 10-13, tardieu2017dentalandextra‐oral pages 1-3) Typically congenital/developmental and recognized in childhood when eruption is delayed or teeth are found to be absent on imaging. Severity is variable but often lifelong.
Dentition Missing permanent teeth / anodontia of permanent dentition HP:0011064 Agenesis of permanent teeth; HP:0009804 Tooth agenesis Yu et al. reported retention of primary teeth with missing permanent teeth in 4/4 OODD patients; bi-allelic WNT10A mutations can cause complete anodontia of permanent teeth (yu2019distinctimpactsof pages 2-3, yu2019distinctimpactsof pages 1-2) Permanent dentition is often more severely affected than primary dentition; developmental, non-remitting course.
Dentition Missing deciduous teeth HP:0006483 Hypodontia of primary teeth In Yu et al. 2019, congenitally missing deciduous teeth were present in all 4 patients, with counts of 4, 2, 2, and 5 missing primary teeth (yu2019distinctimpactsof pages 2-3) Suggests developmental involvement begins early, although primary dentition may be less severely affected than permanent dentition.
Dentition Peg-shaped / conical teeth HP:0006481 Conical tooth; HP:0000698 Peg-shaped teeth Peg-shaped teeth were present in 4/4 OODD patients in Yu et al. 2019; conical primary/permanent anterior teeth also documented in a 2023 WNT10A-deficient case (yu2019distinctimpactsof pages 2-3, garciamartinez2023dentalphenotypewith pages 2-6) Usually evident at eruption in childhood; stable structural abnormality.
Dentition Microdontia HP:0009827 Microdontia Present in 4/4 OODD patients in Yu et al. 2019 (yu2019distinctimpactsof pages 2-3) Developmental size abnormality; often accompanies peg-shaped teeth.
Dentition Enamel hypoplasia HP:0006297 Enamel hypoplasia Present in 3/4 OODD patients in Yu et al. 2019 (yu2019distinctimpactsof pages 2-3) Developmental enamel defect; contributes to attrition and restorative needs.
Dentition Severe tooth wear / attrition HP:0031359 Abnormal tooth wear Severe attrition was present in 4/4 OODD patients in Yu et al. 2019 (yu2019distinctimpactsof pages 2-3) Likely secondary to abnormal enamel and tooth morphology; cumulative over time.
Dentition Retained primary teeth / delayed eruption pattern HP:0006335 Delayed eruption of teeth; HP:0006349 Retained primary teeth Retention of primary teeth with absence of permanent successors emphasized in OODD reports; recent pediatric case required monitoring and prosthetic management for eruption problems (yu2019distinctimpactsof pages 2-3, nurrahma2023prostheticsmanagementof pages 1-2, garciamartinez2023dentalphenotypewith pages 2-6) Usually identified in childhood; may require long-term dental monitoring and intervention.
Dentition Abnormal primary molar morphology HP:0006344 Abnormality of primary teeth; HP:0006489 Abnormal dental morphology Documented in the 2023 case with irregular coronal morphology and highly divergent roots (garciamartinez2023dentalphenotypewith pages 2-6) Developmental anomaly recognized radiographically/clinically in childhood.
Oral cavity Smooth tongue / reduced lingual papillae HP:0010298 Smooth tongue Classic OODD feature in the original family descriptions and broader WNT10A cohorts; also reported in the 2023 case (adaimy2007mutationinwnt10a pages 6-7, bohring2009wnt10amutationsare pages 3-5, garciamartinez2023dentalphenotypewith pages 2-6) Congenital or early-presenting ectodermal manifestation; generally persistent.
Nails Nail dystrophy / onychodysplasia HP:0002164 Nail dysplasia; HP:0008386 Onychodystrophy Dystrophic nails were present in 4/4 OODD patients in Yu et al. 2019; nail dysplasia is a defining OODD feature in discovery and cohort reports (yu2019distinctimpactsof pages 2-3, adaimy2007mutationinwnt10a pages 1-4, bohring2009wnt10amutationsare pages 3-5) Usually congenital or early childhood onset; persistent with variable severity.
Hair Sparse hair / hypotrichosis HP:0001006 Hypotrichosis; HP:0008070 Sparse scalp hair Sparse or dry/thin hair is a core OODD feature; Yu et al. and multiple cohort reports describe sparse hair, while original families noted very slow-growing short hair (yu2019distinctimpactsof pages 1-2, bohring2009wnt10amutationsare pages 3-5, adaimy2007mutationinwnt10a pages 6-7) Often apparent in infancy/childhood; chronic, non-progressive or slowly evolving.
Hair Sparse eyebrows HP:0000647 Sparse eyebrow Reported in WNT10A/OODD spectrum cohorts and the 2023 case (bohring2009wnt10amutationsare pages 3-5, garciamartinez2023dentalphenotypewith pages 2-6) Mild-to-moderate ectodermal manifestation; usually persistent.
Skin (palms/soles) Palmoplantar keratoderma / hyperkeratosis HP:0000982 Palmoplantar keratoderma; HP:0000957 Palmoplantar hyperkeratosis In Yu et al. 2019, palmar hyperkeratosis occurred in 3/4 and plantar hyperkeratosis in 3/4; original and later cohorts describe palmoplantar keratoderma as characteristic (yu2019distinctimpactsof pages 2-3, adaimy2007mutationinwnt10a pages 1-4, bohring2009wnt10amutationsare pages 3-5) Often develops in childhood; may be painful when severe and can impair comfort/walking.
Skin Dry skin / xerosis HP:0001021 Hyperkeratosis; HP:0000958 Dry skin Dry skin/xerosis reported in WNT10A cohorts and classic OODD descriptions (bohring2009wnt10amutationsare pages 3-5, tardieu2017dentalandextra‐oral pages 10-13) Chronic ectodermal sign; may fluctuate with environment but generally persistent.
Sweating Hypohidrosis HP:0000979 Hypohidrosis Present in 2/4 OODD patients in Yu et al. 2019; sweating dysfunction is part of the OODD spectrum (yu2019distinctimpactsof pages 2-3, yu2019distinctimpactsof pages 1-2) Variable expressivity; can contribute to heat intolerance.
Sweating Hyperhidrosis (especially palms/soles) HP:0000975 Hyperhidrosis; HP:0007428 Palmoplantar hyperhidrosis Hyperhidrosis of palms and soles was part of the original OODD description and broader WNT10A cohort spectrum (adaimy2007mutationinwnt10a pages 1-4, bohring2009wnt10amutationsare pages 3-5) Variable even within families; may be worse at night or in warm environments.
Face / skin Facial telangiectasia / atrophic facial patches HP:0001009 Telangiectasia; HP:0001070 Atrophic skin patches Bohring and Yu describe erythematous/atrophic facial lesions; the 2023 WNT10A-deficient case had facial telangiectases (bohring2009wnt10amutationsare pages 3-5, yu2019distinctimpactsof pages 1-2, garciamartinez2023dentalphenotypewith pages 2-6) Variable and not universal; tends to be a stable ectodermal skin finding.
Functional impact Painful fissures/lacerations of palms/soles HP:0001071 Fissured skin Painful palmoplantar lacerations were described in the WNT10A cohort spectrum (bohring2009wnt10amutationsare pages 3-5) Important quality-of-life impact when keratoderma is severe; may affect mobility/manual function.
Functional impact Heat intolerance / discomfort in warm temperatures HP:0002046 Heat intolerance Reported in cohort descriptions as discomfort at temperatures above 25°C in some affected individuals (bohring2009wnt10amutationsare pages 3-5) Likely related to sweating dysfunction; episodic environmental trigger rather than progressive disease feature.

Table: This table maps major odonto-onycho-dermal dysplasia features to suggested HPO terms using only the cited evidence. It highlights which findings are core versus variable, and includes available frequency data such as the 4-patient OODD series from Yu et al. 2019.

4. Genetic / Molecular Information

4.1 Causal gene

4.2 Pathogenic variants (examples from primary literature)

Reported OODD-associated WNT10A variants span nonsense and frameshift loss-of-function and deleterious missense alleles.

Key examples from the retrieved evidence include: - c.697G>T (p.Glu233X) recurrent homozygous nonsense variant in Lebanese families (2007). (adaimy2007mutationinwnt10a pages 4-6) - Additional variants reported in a 2009 spectrum study (e.g., c.27G>A (p.W9X); c.321C>A (p.C107X); c.1128C>A (p.C376X); c.383G>A (p.R128Q); c.682T>A (p.F228I)). (bohring2009wnt10amutationsare pages 1-3) - 2019 report of five novel variants, including truncating and frameshift alleles (e.g., c.742C>T (p.Arg248*), c.1176C>A (p.Cys392*), c.898-899delAT (p.Ile300Profs*126)). (yu2019distinctimpactsof pages 1-2)

A concise evidence-constrained variant table is provided below.

Table (click to expand)
Category Item Details Publication / URL Evidence
Identifier Disease name Odonto-onycho-dermal dysplasia (OODD) Adaimy et al., 2007; https://doi.org/10.1086/520064 (yu2019distinctimpactsof pages 1-2, adaimy2007mutationinwnt10a pages 1-4)
Identifier OMIM/MIM disease number MIM/OMIM #257980 Yu et al., 2019; https://doi.org/10.1002/ajmg.a.60682 (yu2019distinctimpactsof pages 1-2, bohring2009wnt10amutationsare pages 1-3)
Genetic basis Inheritance Autosomal recessive Adaimy et al., 2007; https://doi.org/10.1086/520064 (yu2019distinctimpactsof pages 1-2, adaimy2007mutationinwnt10a pages 1-4, bohring2009wnt10amutationsare pages 1-3)
Genetic basis Causal gene WNT10A Adaimy et al., 2007; https://doi.org/10.1086/520064 (yu2019distinctimpactsof pages 1-2, adaimy2007mutationinwnt10a pages 1-4, bohring2009wnt10amutationsare pages 1-3)
Genetic basis WNT10A OMIM gene number OMIM/MIM *606268 Yu et al., 2019; https://doi.org/10.1002/ajmg.a.60682 (yu2019distinctimpactsof pages 1-2, bohring2009wnt10amutationsare pages 1-3)
Clinical features Hallmark features Severe hypodontia/oligodontia or tooth agenesis, peg-shaped/conical teeth, enamel hypoplasia, retained primary teeth, nail dystrophy/onychodysplasia, dry or sparse hair/hypotrichosis, palmoplantar keratoderma/hyperkeratosis, sweating abnormalities (hyperhidrosis or hypohidrosis), smooth tongue with reduced papillae Adaimy et al., 2007; https://doi.org/10.1086/520064 (yu2019distinctimpactsof pages 1-2, adaimy2007mutationinwnt10a pages 1-4, bohring2009wnt10amutationsare pages 1-3, adaimy2007mutationinwnt10a pages 4-6)
Pathogenic WNT10A variants Recurrent founder-like variant c.697G>T, p.Glu233X (reported as recurrent homozygous nonsense variant in three Lebanese families) Adaimy et al., 2007; https://doi.org/10.1086/520064 (adaimy2007mutationinwnt10a pages 1-4, adaimy2007mutationinwnt10a pages 4-6)
Pathogenic WNT10A variants Truncating variant c.27G>A, p.W9X Bohring et al., 2009; https://doi.org/10.1016/j.ajhg.2009.06.001 (bohring2009wnt10amutationsare pages 1-3)
Pathogenic WNT10A variants Truncating variant c.321C>A, p.C107X Bohring et al., 2009; https://doi.org/10.1016/j.ajhg.2009.06.001 (bohring2009wnt10amutationsare pages 1-3)
Pathogenic WNT10A variants Truncating variant c.1128C>A, p.C376X Bohring et al., 2009; https://doi.org/10.1016/j.ajhg.2009.06.001 (bohring2009wnt10amutationsare pages 1-3)
Pathogenic WNT10A variants Missense variant c.383G>A, p.R128Q Bohring et al., 2009; https://doi.org/10.1016/j.ajhg.2009.06.001 (bohring2009wnt10amutationsare pages 1-3)
Pathogenic WNT10A variants Missense variant c.682T>A, p.F228I Bohring et al., 2009; https://doi.org/10.1016/j.ajhg.2009.06.001 (bohring2009wnt10amutationsare pages 1-3)
Pathogenic WNT10A variants Novel truncating variant c.1176C>A, p.Cys392* Yu et al., 2019; https://doi.org/10.1002/ajmg.a.60682 (yu2019distinctimpactsof pages 1-2)
Pathogenic WNT10A variants Novel truncating variant c.742C>T, p.Arg248* Yu et al., 2019; https://doi.org/10.1002/ajmg.a.60682 (yu2019distinctimpactsof pages 1-2)
Pathogenic WNT10A variants Novel frameshift variant c.898-899delAT, p.Ile300Profs*126 Yu et al., 2019; https://doi.org/10.1002/ajmg.a.60682 (yu2019distinctimpactsof pages 1-2)
Pathogenic WNT10A variants Novel compound-heterozygous variant c.826T>A, p.Cys276Ser Yu et al., 2019; https://doi.org/10.1002/ajmg.a.60682 (yu2019distinctimpactsof pages 1-2)
Pathogenic WNT10A variants Novel compound-heterozygous variant c.949delG, p.Ala317Hisfs*121 Yu et al., 2019; https://doi.org/10.1002/ajmg.a.60682 (yu2019distinctimpactsof pages 1-2)
Recent related WNT10A deficiency report Compound-heterozygous pathogenic variants in a mild ectodermal phenotype suggestive of WNT10A deficiency c.310C>T, p.Arg104Cys; c.742C>T, p.Arg248Ter García-Martínez et al., 2023; https://doi.org/10.3390/children10020356 (garciamartinez2023dentalphenotypewith pages 1-2, garciamartinez2023dentalphenotypewith pages 2-6)

Table: This table compiles only evidence-supported identifiers, hallmark features, and reported WNT10A variants for odonto-onycho-dermal dysplasia from the retrieved snippets. It is useful as a citation-ready summary for disease knowledge base curation.

4.3 Functional consequence (current understanding)

The clinical genetics evidence supports primarily loss-of-function mechanisms: truncating variants (nonsense/frameshift) and deleterious missense variants affecting conserved residues (often in compound heterozygosity with truncating alleles) are associated with OODD. (bohring2009wnt10amutationsare pages 1-3, tardieu2017dentalandextra‐oral pages 10-13)

4.4 Epigenetics, chromosomal abnormalities, modifier genes

5. Environmental Information

No specific environmental or lifestyle contributors were identified in the retrieved OODD evidence. OODD is supported as a primarily genetic developmental disorder due to WNT10A variants. (adaimy2007mutationinwnt10a pages 1-4, bohring2009wnt10amutationsare pages 1-3)

6. Mechanism / Pathophysiology

6.1 Pathway-level mechanism

WNT10A is a Wnt ligand acting through canonical Wnt/β-catenin signaling: - Wnt proteins inhibit the β-catenin degradation complex; stabilized β-catenin partners with LEF/TCF transcription factors to regulate target gene expression. (bohring2009wnt10amutationsare pages 1-3) - Wnt binds Frizzled and LRP5/6, stabilizes β-catenin, and via LEF-1/TCF can induce downstream osteogenic programs (e.g., RUNX2). (tardieu2017dentalandextra‐oral pages 3-7)

This signaling is central to odontogenesis and ectodermal appendage development, consistent with the restriction of clinical phenotypes to ectoderm-derived organs. (bohring2009wnt10amutationsare pages 1-3, yu2019distinctimpactsof pages 2-3)

6.2 Tissue/cell types implicated (ontology suggestions)

Primary tissues/organs (UBERON suggestions): - Tooth (UBERON:0001091) - Nail (UBERON:0001705) - Skin (UBERON:0002097) - Hair follicle (UBERON:0001034) - Tongue (UBERON:0001723)

Cell types (CL suggestions) (inferred from described organ involvement and Wnt pathway context): - Ameloblast (CL:0000148) (enamel defects) - Odontoblast (CL:0000138) (dentin/root phenotypes; odontoblast-region expression described) (yoshinaga2023effectsofwnt10a pages 1-2) - Keratinocyte (CL:0000312) (skin/nail/hair phenotypes)

GO biological process suggestions (based on pathway descriptions): - Canonical Wnt signaling pathway (GO:0060070) - Tooth development (GO:0042476) - Hair follicle development (GO:0001942) - Keratinization (GO:0031424)

6.3 Protein features relevant to disease

WNT10A has a signal peptide (aa 1–35) and a Wnt domain (aa 60–417); disease-associated mutations include truncating variants expected to disrupt these functional regions, supporting a loss-of-function model. (bohring2009wnt10amutationsare pages 1-3)

6.4 Model organism evidence

  • A wnt10a−/− mouse shows dental anomalies including molar microdontia, reduced cusp number, taurodontism and (in some reports) supernumerary molars, indicating conserved involvement of Wnt10a in odontogenesis with notable species differences from human tooth agenesis. (tardieu2017dentalandextra‐oral pages 10-13)
  • Wnt10a/Wnt10b double mutants show severe enamel/root hypoplasia; double knockouts can exhibit a decreased number of teeth (e.g., missing upper incisor or third molar), consistent with functional redundancy. (yoshinaga2023effectsofwnt10a pages 1-2)

7. Anatomical Structures Affected

7.1 Organ systems

Primary affected systems are integumentary and craniofacial/odontogenic: - Dentition (tooth agenesis, abnormal morphology) (yu2019distinctimpactsof pages 2-3) - Skin/palms/soles (keratoderma, xerosis) (bohring2009wnt10amutationsare pages 3-5) - Nails (dystrophy) (yu2019distinctimpactsof pages 2-3) - Hair/eyebrows (hypotrichosis) (bohring2009wnt10amutationsare pages 3-5) - Tongue (smooth tongue due to papillae reduction) (bohring2009wnt10amutationsare pages 3-5)

Secondary/variable involvement: skeletal/cartilaginous anomalies and other extra-ectodermal findings have been described in WNT10A cohorts (~10% for major skeletal/cartilaginous defects). (tardieu2017dentalandextra‐oral pages 10-13)

8. Temporal Development

OODD is a congenital/developmental condition with manifestations becoming apparent in infancy/childhood as dentition, hair, nails, and skin appendages develop. In one cohort description, early eruption timing of primary teeth (4–10 months) is reported in affected infants, and palmoplantar hyperkeratosis may develop around early childhood. (bohring2009wnt10amutationsare pages 3-5, adaimy2007mutationinwnt10a pages 1-4)

9. Inheritance and Population

9.1 Inheritance

OODD is autosomal recessive due to biallelic WNT10A variants. (adaimy2007mutationinwnt10a pages 1-4, yu2019distinctimpactsof pages 1-2)

9.2 Population and carrier manifestations

Heterozygous carriers may show milder manifestations; in one ectodermal dysplasia cohort, ~53.8% of heterozygotes showed phenotype manifestations with sex-biased patterns. (bohring2009wnt10amutationsare pages 1-3)

Note: Variant-specific geographic distributions and founder effects were not systematically extractable from the retrieved excerpts beyond the original observation of a recurrent variant in three families from the same community. (adaimy2007mutationinwnt10a pages 4-6)

10. Diagnostics

10.1 Clinical and radiographic evaluation

Typical work-up includes clinical examination of ectodermal structures and dental imaging (panoramic radiographs) to document absent/retained teeth and morphology. (yu2019distinctimpactsof pages 2-3)

10.2 Genetic testing approaches (real-world implementations)

Approaches documented across studies include: - Homozygosity mapping + Sanger sequencing in consanguineous families to identify WNT10A founder variants. (adaimy2007mutationinwnt10a pages 1-4) - Targeted PCR/Sanger sequencing of WNT10A with segregation analysis. (bohring2009wnt10amutationsare pages 1-3, tardieu2017dentalandextra‐oral pages 3-7) - Gene panels (e.g., orodental NGS panel) in some families. (tardieu2017dentalandextra‐oral pages 3-7) - Whole-exome sequencing (WES) in 2024 digenic HED report with ACMG-based evaluation. (liu2024compoundheterozygouswnt10a pages 1-2)

10.3 Differential diagnosis

A key differential is Schöpf–Schulz–Passarge syndrome (SSPS), which overlaps clinically with OODD but is characterized by multiple eyelid cysts / apocrine hidrocystomas and has been associated with increased risk of skin tumors. The absence of eyelid cysts is used to favor an OODD diagnosis in WNT10A-related cases. (tardieu2017dentalandextra‐oral pages 1-3, yu2019distinctimpactsof pages 2-3, bohring2009wnt10amutationsare pages 1-3)

11. Outcome / Prognosis

OODD is generally compatible with normal growth and neurodevelopment in reported families, but is a chronic lifelong disorder requiring ongoing dental/dermatologic care (e.g., “Growth and mental development were normal”). (adaimy2007mutationinwnt10a pages 1-4)

Major determinants of morbidity are functional and psychosocial impacts of severe tooth agenesis, chewing/speech/aesthetic challenges, and skin/nail/hair symptoms. Formal survival or mortality statistics were not identified in the retrieved excerpts. (bohring2009wnt10amutationsare pages 3-5, nurrahma2023prostheticsmanagementof pages 1-2)

12. Treatment

12.1 Current standard of care

No curative therapy is described; management is supportive and multidisciplinary. A recent report states: “Currently there is no curative treatment for OODD. Multidisciplinary supportive management remains the gold standard.” (kalaszi2026casereportnovel pages 2-4)

12.2 Dental/prosthetic rehabilitation (real-world implementations; 2023 emphasis)

  • 2023 pediatric OODD case report (Journal of Dentomaxillofacial Science; Dec 2023; https://doi.org/10.15562/jdmfs.v8i3.1638): a 12-year-old received removable dentures (maxillary and mandibular). Reported short-term outcomes included eruption of maxillary molars after 3 months, followed by denture perforation to accommodate erupting teeth; mandibular premolars erupted by ~1 month later, with surgical exposure used to accelerate eruption. The authors emphasize interdisciplinary therapy. (nurrahma2023prostheticsmanagementof pages 1-2)
  • Monitoring and planning: a 2023 WNT10A-deficient oligodontia case was monitored for jaw growth and planned future rehabilitation rather than immediate definitive prosthetics. (garciamartinez2023dentalphenotypewith pages 2-6)

MAXO suggestions (inferred for management actions described): - Dental prosthesis therapy (MAXO term suggestion for removable dentures) - Surgical exposure of tooth (MAXO term suggestion) - Dental surveillance/monitoring (MAXO term suggestion)

12.3 Pharmacotherapy / advanced therapeutics

No OODD-specific pharmacologic or gene therapies were identified in the retrieved evidence. A case report references emerging regenerative approaches and related prenatal EDA trials in XLHED, but these are not OODD-specific. (kalaszi2026casereportnovel pages 2-4)

12.4 Clinical trials

A ClinicalTrials.gov search for “WNT10A”/“odonto-onycho-dermal dysplasia” did not identify OODD-targeted interventional trials in the retrieved trial set. (adaimy2007mutationinwnt10a media 078cd7b3)

13. Prevention

No primary prevention is available for a congenital Mendelian disorder; prevention focuses on: - Genetic counseling for recurrence risk in families with identified WNT10A variants, and cascade testing of relatives (noted in clinical genetics practice in recent case-based reports). (kalaszi2026casereportnovel pages 2-4) - Secondary/tertiary prevention of complications: early dental evaluation, caries prevention, and proactive prosthetic/orthodontic planning to reduce functional and psychosocial burden. (nurrahma2023prostheticsmanagementof pages 3-4)

14. Other Species / Natural Disease

Naturally occurring OODD analogs in non-human species were not identified in the retrieved excerpts.

15. Model Organisms

Mouse models

  • Wnt10a knockout mice: enamel hypoplasia, altered tooth shape, taurodontic roots; unexpected supernumerary teeth reported, highlighting species differences and pathway complexity. (yoshinaga2023effectsofwnt10a pages 2-4)
  • Wnt10a/Wnt10b double mutants: severe enamel/root hypoplasia and reduced tooth number in double knockouts, supporting redundancy between paralogs. (yoshinaga2023effectsofwnt10a pages 1-2)

Key visual evidence

A key figure/table set in the original gene-discovery report includes: - Table summarizing OODD clinical features across families and sequencing chromatograms for the c.697G>T (p.Glu233X) mutation (adaimy2007mutationinwnt10a media 78f3e813, adaimy2007mutationinwnt10a media beb3a4f1).

Summary of key 2023–2024 developments

Limitations of this evidence set

This report is limited to the retrieved primary texts and excerpts. Several requested identifiers (Orphanet/ICD/MeSH), formal prevalence/incidence estimates for OODD specifically, and rigorous QoL metrics were not present in the available excerpts and therefore are not asserted.

References

  1. (adaimy2007mutationinwnt10a pages 1-4): Lynn Adaimy, Eliane Chouery, Hala Mégarbané, Salman Mroueh, Valérie Delague, Elsa Nicolas, Hanen Belguith, Philippe de Mazancourt, and André Mégarbané. Mutation in wnt10a is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. American journal of human genetics, 81 4:821-8, Oct 2007. URL: https://doi.org/10.1086/520064, doi:10.1086/520064. This article has 315 citations and is from a highest quality peer-reviewed journal.

  2. (bohring2009wnt10amutationsare pages 1-3): Axel Bohring, Thomas Stamm, Christiane Spaich, Claudia Haase, Kerstin Spree, Ute Hehr, Mandy Hoffmann, Susanne Ledig, Saadettin Sel, Peter Wieacker, and Albrecht Röpke. Wnt10a mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes. American journal of human genetics, 85 1:97-105, Jul 2009. URL: https://doi.org/10.1016/j.ajhg.2009.06.001, doi:10.1016/j.ajhg.2009.06.001. This article has 275 citations and is from a highest quality peer-reviewed journal.

  3. (yu2019distinctimpactsof pages 1-2): Miao Yu, Yang Liu, Haochen Liu, Sing‐Wai Wong, Huiying He, Xiaoxia Zhang, Yue Wang, Dong Han, and Hailan Feng. Distinct impacts of bi‐allelic wnt10a mutations on the permanent and primary dentitions in odonto‐onycho‐dermal dysplasia. American Journal of Medical Genetics Part A, 179:57-64, Jan 2019. URL: https://doi.org/10.1002/ajmg.a.60682, doi:10.1002/ajmg.a.60682. This article has 43 citations.

  4. (kalaszi2026casereportnovel pages 1-2): Marianna Kalaszi, Ciaran Moore, Chrysoula Koniari, and Theodoros Mavridis. Case report: novel pathogenic variant in autosomal recessive wnt10a-related odonto-onycho-dermal dysplasia. Frontiers in Genetics, Mar 2026. URL: https://doi.org/10.3389/fgene.2026.1750692, doi:10.3389/fgene.2026.1750692. This article has 0 citations and is from a peer-reviewed journal.

  5. (tardieu2017dentalandextra‐oral pages 1-3): C. Tardieu, Sophie Jung, K. Niederreither, Megana K. Prasad, S. Hadj-Rabia, N. Philip, A. Mallet, É. Consolino, E. Sfeir, B. Noueiri, N. Chassaing, H. Dollfus, M. Manière, M. Manière, A. Bloch-Zupan, and F. Clauss. Dental and extra‐oral clinical features in 41 patients with wnt10a gene mutations: a multicentric genotype–phenotype study. Clinical Genetics, 92:477-486, Nov 2017. URL: https://doi.org/10.1111/cge.12972, doi:10.1111/cge.12972. This article has 34 citations and is from a peer-reviewed journal.

  6. (tardieu2017dentalandextra‐oral pages 10-13): C. Tardieu, Sophie Jung, K. Niederreither, Megana K. Prasad, S. Hadj-Rabia, N. Philip, A. Mallet, É. Consolino, E. Sfeir, B. Noueiri, N. Chassaing, H. Dollfus, M. Manière, M. Manière, A. Bloch-Zupan, and F. Clauss. Dental and extra‐oral clinical features in 41 patients with wnt10a gene mutations: a multicentric genotype–phenotype study. Clinical Genetics, 92:477-486, Nov 2017. URL: https://doi.org/10.1111/cge.12972, doi:10.1111/cge.12972. This article has 34 citations and is from a peer-reviewed journal.

  7. (yoshinaga2023effectsofwnt10a pages 2-4): Kaoru Yoshinaga, Akihiro Yasue, Silvia Naomi Mitsui, Yoshiyuki Minegishi, Seiichi Oyadomari, Issei Imoto, and Eiji Tanaka. Effects of wnt10a and wnt10b double mutations on tooth development. Genes, 14:340, Jan 2023. URL: https://doi.org/10.3390/genes14020340, doi:10.3390/genes14020340. This article has 7 citations.

  8. (adaimy2007mutationinwnt10a pages 4-6): Lynn Adaimy, Eliane Chouery, Hala Mégarbané, Salman Mroueh, Valérie Delague, Elsa Nicolas, Hanen Belguith, Philippe de Mazancourt, and André Mégarbané. Mutation in wnt10a is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. American journal of human genetics, 81 4:821-8, Oct 2007. URL: https://doi.org/10.1086/520064, doi:10.1086/520064. This article has 315 citations and is from a highest quality peer-reviewed journal.

  9. (garciamartinez2023dentalphenotypewith pages 1-2): Victoria-Eugenia García-Martínez, Ximo Galiana-Vallés, Otilia Zomeño-Alcalá, Raquel Rodríguez-López, Carmen Llena, María del Carmen Martínez-Romero, and Encarna Guillén-Navarro. Dental phenotype with minor ectodermal symptoms suggestive of wnt10a deficiency. Children, 10:356, Feb 2023. URL: https://doi.org/10.3390/children10020356, doi:10.3390/children10020356. This article has 1 citations.

  10. (liu2024compoundheterozygouswnt10a pages 1-2): Yiting Liu, Jing Sun, Caiqi Zhang, Yi Wu, Siyuan Ma, Xuechun Li, Xiaoshan Wu, and Qingping Gao. Compound heterozygous wnt10a missense variations exacerbated the tooth agenesis caused by hypohidrotic ectodermal dysplasia. BMC Oral Health, Jan 2024. URL: https://doi.org/10.1186/s12903-024-03888-5, doi:10.1186/s12903-024-03888-5. This article has 6 citations and is from a peer-reviewed journal.

  11. (yu2019distinctimpactsof pages 2-3): Miao Yu, Yang Liu, Haochen Liu, Sing‐Wai Wong, Huiying He, Xiaoxia Zhang, Yue Wang, Dong Han, and Hailan Feng. Distinct impacts of bi‐allelic wnt10a mutations on the permanent and primary dentitions in odonto‐onycho‐dermal dysplasia. American Journal of Medical Genetics Part A, 179:57-64, Jan 2019. URL: https://doi.org/10.1002/ajmg.a.60682, doi:10.1002/ajmg.a.60682. This article has 43 citations.

  12. (bohring2009wnt10amutationsare pages 3-5): Axel Bohring, Thomas Stamm, Christiane Spaich, Claudia Haase, Kerstin Spree, Ute Hehr, Mandy Hoffmann, Susanne Ledig, Saadettin Sel, Peter Wieacker, and Albrecht Röpke. Wnt10a mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes. American journal of human genetics, 85 1:97-105, Jul 2009. URL: https://doi.org/10.1016/j.ajhg.2009.06.001, doi:10.1016/j.ajhg.2009.06.001. This article has 275 citations and is from a highest quality peer-reviewed journal.

  13. (garciamartinez2023dentalphenotypewith pages 2-6): Victoria-Eugenia García-Martínez, Ximo Galiana-Vallés, Otilia Zomeño-Alcalá, Raquel Rodríguez-López, Carmen Llena, María del Carmen Martínez-Romero, and Encarna Guillén-Navarro. Dental phenotype with minor ectodermal symptoms suggestive of wnt10a deficiency. Children, 10:356, Feb 2023. URL: https://doi.org/10.3390/children10020356, doi:10.3390/children10020356. This article has 1 citations.

  14. (nurrahma2023prostheticsmanagementof pages 1-2): Rifaat Nurrahma, Syakriani Syahrir, Muhammad Ikbal, Edy Machmud, Irfan Dammar, Acing H. Mude, Ike D. Habar, Ludfia Ulfa, Nurimah Wahyuni, and Ainun Bazira. Prosthetics management of odonto-onycho-dermal dysplasia pediatric patient: a case report. Journal of Dentomaxillofacial Science, 8:196-199, Dec 2023. URL: https://doi.org/10.15562/jdmfs.v8i3.1638, doi:10.15562/jdmfs.v8i3.1638. This article has 0 citations.

  15. (adaimy2007mutationinwnt10a pages 6-7): Lynn Adaimy, Eliane Chouery, Hala Mégarbané, Salman Mroueh, Valérie Delague, Elsa Nicolas, Hanen Belguith, Philippe de Mazancourt, and André Mégarbané. Mutation in wnt10a is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. American journal of human genetics, 81 4:821-8, Oct 2007. URL: https://doi.org/10.1086/520064, doi:10.1086/520064. This article has 315 citations and is from a highest quality peer-reviewed journal.

  16. (tardieu2017dentalandextra‐oral pages 3-7): C. Tardieu, Sophie Jung, K. Niederreither, Megana K. Prasad, S. Hadj-Rabia, N. Philip, A. Mallet, É. Consolino, E. Sfeir, B. Noueiri, N. Chassaing, H. Dollfus, M. Manière, M. Manière, A. Bloch-Zupan, and F. Clauss. Dental and extra‐oral clinical features in 41 patients with wnt10a gene mutations: a multicentric genotype–phenotype study. Clinical Genetics, 92:477-486, Nov 2017. URL: https://doi.org/10.1111/cge.12972, doi:10.1111/cge.12972. This article has 34 citations and is from a peer-reviewed journal.

  17. (yoshinaga2023effectsofwnt10a pages 1-2): Kaoru Yoshinaga, Akihiro Yasue, Silvia Naomi Mitsui, Yoshiyuki Minegishi, Seiichi Oyadomari, Issei Imoto, and Eiji Tanaka. Effects of wnt10a and wnt10b double mutations on tooth development. Genes, 14:340, Jan 2023. URL: https://doi.org/10.3390/genes14020340, doi:10.3390/genes14020340. This article has 7 citations.

  18. (kalaszi2026casereportnovel pages 2-4): Marianna Kalaszi, Ciaran Moore, Chrysoula Koniari, and Theodoros Mavridis. Case report: novel pathogenic variant in autosomal recessive wnt10a-related odonto-onycho-dermal dysplasia. Frontiers in Genetics, Mar 2026. URL: https://doi.org/10.3389/fgene.2026.1750692, doi:10.3389/fgene.2026.1750692. This article has 0 citations and is from a peer-reviewed journal.

  19. (adaimy2007mutationinwnt10a media 078cd7b3): Lynn Adaimy, Eliane Chouery, Hala Mégarbané, Salman Mroueh, Valérie Delague, Elsa Nicolas, Hanen Belguith, Philippe de Mazancourt, and André Mégarbané. Mutation in wnt10a is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. American journal of human genetics, 81 4:821-8, Oct 2007. URL: https://doi.org/10.1086/520064, doi:10.1086/520064. This article has 315 citations and is from a highest quality peer-reviewed journal.

  20. (nurrahma2023prostheticsmanagementof pages 3-4): Rifaat Nurrahma, Syakriani Syahrir, Muhammad Ikbal, Edy Machmud, Irfan Dammar, Acing H. Mude, Ike D. Habar, Ludfia Ulfa, Nurimah Wahyuni, and Ainun Bazira. Prosthetics management of odonto-onycho-dermal dysplasia pediatric patient: a case report. Journal of Dentomaxillofacial Science, 8:196-199, Dec 2023. URL: https://doi.org/10.15562/jdmfs.v8i3.1638, doi:10.15562/jdmfs.v8i3.1638. This article has 0 citations.

  21. (adaimy2007mutationinwnt10a media 78f3e813): Lynn Adaimy, Eliane Chouery, Hala Mégarbané, Salman Mroueh, Valérie Delague, Elsa Nicolas, Hanen Belguith, Philippe de Mazancourt, and André Mégarbané. Mutation in wnt10a is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. American journal of human genetics, 81 4:821-8, Oct 2007. URL: https://doi.org/10.1086/520064, doi:10.1086/520064. This article has 315 citations and is from a highest quality peer-reviewed journal.

  22. (adaimy2007mutationinwnt10a media beb3a4f1): Lynn Adaimy, Eliane Chouery, Hala Mégarbané, Salman Mroueh, Valérie Delague, Elsa Nicolas, Hanen Belguith, Philippe de Mazancourt, and André Mégarbané. Mutation in wnt10a is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. American journal of human genetics, 81 4:821-8, Oct 2007. URL: https://doi.org/10.1086/520064, doi:10.1086/520064. This article has 315 citations and is from a highest quality peer-reviewed journal.