Odonto-Onycho-Dermal Dysplasia

👪

Inheritance

1

Autosomal recessive HP:0000007

OODD and SSPS follow autosomal recessive inheritance. However, heterozygous carriers frequently manifest tooth agenesis and mild ectodermal features (semi-dominant with variable penetrance), making WNT10A one of the few ectodermal dysplasia genes with significant heterozygote phenotypic effects.

Autosomal recessive inheritance

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Subtypes

3

Odonto-Onycho-Dermal Dysplasia (Classic)

Classic autosomal recessive presentation with severe oligodontia or anodontia, onychodysplasia, palmoplantar keratoderma, hyperhidrosis of palms and soles, and dry sparse hair. Caused by biallelic WNT10A loss-of-function mutations.

Show evidence (1 reference)

PMID:17847007 SUPPORT Human Clinical

"Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of..."

Defines the cardinal features of OODD including dental, nail, skin, and hair abnormalities.

Schopf-Schulz-Passarge Syndrome MONDO:0009145

The most severe end of the WNT10A spectrum. Includes all features of OODD plus multiple eyelid apocrine hidrocystomas (cysts). Also autosomal recessive with biallelic WNT10A mutations.

Show evidence (2 references)

PMID:19559398 SUPPORT Human Clinical

"WNT10A mutations cause not only OODD but also other forms of ectodermal dysplasia, reaching from apparently monosymptomatic severe oligodontia to Schöpf-Schulz-Passarge syndrome, which is so far considered a unique entity by the findings of numerous cysts along eyelid margins and the increased..."

Demonstrates that SSPS is part of the WNT10A mutation spectrum, distinguished by eyelid margin cysts and skin tumor risk.

PMID:24398796 SUPPORT Human Clinical

"We conclude that OODD and SSPS should be considered as variable expressions of the same WNT10A genotype. "

Confirms that OODD and SSPS are phenotypic variants of the same molecular cause rather than distinct genetic entities.

Selective Tooth Agenesis Type 4 MONDO:0007881

The mildest phenotype in the WNT10A spectrum. Heterozygous (monoallelic) WNT10A mutations cause isolated tooth agenesis, most commonly affecting mandibular second premolars and maxillary lateral incisors. Autosomal dominant inheritance with variable expressivity.

Show evidence (1 reference)

PMID:22581971 SUPPORT Human Clinical

"WNT10A mutations were identified in 56% of the cases with non-syndromic hypodontia. MSX1, PAX9 and AXIN2 mutations were present in 3%, 9% and 3% of the cases, respectively. "

Demonstrates that WNT10A is the most commonly mutated gene in isolated hypodontia, responsible for more than half of cases.

⚙

Pathophysiology

2

WNT10A Loss of Function

WNT10A encodes a secreted glycoprotein ligand of the canonical WNT signaling pathway. Loss-of-function mutations abolish WNT10A binding to Frizzled receptors, preventing activation of the beta-catenin destruction complex inhibition and downstream TCF/LEF-mediated transcription. This disrupts ectodermal appendage morphogenesis including teeth, hair follicles, nails, and sweat glands.

ectodermal cell link ameloblast link odontoblast link

canonical Wnt signaling pathway link odontogenesis link ↓ DECREASED hair follicle development link ↓ DECREASED

Downstream

Ectodermal Appendage Defects

Show evidence (3 references)

PMID:17847007 SUPPORT Human Clinical

"This is the first report to our knowledge of a human phenotype resulting from a mutation in WNT10A, and it is the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, expanding the list of WNT-related diseases. "

Establishes WNT10A as the causative gene for OODD and links WNT signaling disruption to ectodermal dysplasia.

PMID:19471313 SUPPORT Human Clinical

"WNT10A is expressed in the skin and epidermis and it has shown to be critical for the development of ectodermal appendages. "

Confirms WNT10A expression in skin/epidermis and its critical role in ectodermal appendage development.

PMID:28105635 SUPPORT Human Clinical

"WNT10A gene encodes a canonical wingless pathway signaling molecule involved in cell fate specification as well as morphogenetic patterning of the developing ectoderm, nervous system, skeleton, and tooth. "

Confirms WNT10A role in canonical Wnt pathway and morphogenetic patterning of ectoderm and tooth.

Ectodermal Appendage Defects

Disrupted WNT/beta-catenin signaling during embryonic development leads to hypoplasia or aplasia of ectodermal appendages. Teeth are most severely affected (oligodontia/anodontia), followed by nails (dystrophy, thinning), hair (sparse, dry), and sweat glands (hypohidrosis or paradoxical hyperhidrosis of palms/soles).

keratinocyte link

ectodermal placode formation link ↓ DECREASED epidermis development link

Show evidence (1 reference)

PMID:26964878 SUPPORT Human Clinical

"Odonto-onycho-dermal dysplasia (OODD) is a rare form of ectodermal dysplasia characterized by severe oligodontia, onychodysplasia, palmoplantar hyperkeratosis, dry skin, hypotrichosis, and hyperhidrosis of the palms and soles. "

Summarizes the spectrum of ectodermal appendage defects seen in OODD including teeth, nails, skin, and hair.

✶

Histopathology

1

Eccrine Syringofibroadenomatosis

Skin biopsies from hyperkeratotic palms and soles show characteristic changes of eccrine syringofibroadenomatosis, a histopathological finding described in patients with ectodermal dysplasias.

Show evidence (1 reference)

PMID:26964878 SUPPORT Human Clinical

"Skin biopsies from the hyperkeratotic palms and soles showed the characteristic changes of eccrine syringofibroadenomatosis, which has been described in patients with ectodermal dysplasias. "

Documents eccrine syringofibroadenomatosis as a characteristic histopathological finding in OODD skin biopsies.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

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Phenotypes

12

Head and Neck 2

Oligodontia VERY_FREQUENT Oligodontia (HP:0000677)

Show evidence (2 references)

PMID:28105635 SUPPORT Human Clinical

"Mild to severe oligodontia was observed in all patients bearing biallelic WNT10A mutations. "

Demonstrates that oligodontia is universal in biallelic WNT10A mutation carriers in a 41-patient cohort.

PMID:24700731 SUPPORT Human Clinical

"Patients with bi-allelic WNT10A mutations have severe tooth agenesis while heterozygous individuals are either unaffected or have a mild phenotype. "

Confirms genotype-phenotype correlation between biallelic mutations and severe tooth agenesis.

Abnormal Tooth Morphology FREQUENT Abnormal dental morphology (HP:0006482)

Show evidence (1 reference)

PMID:28105635 SUPPORT Human Clinical

"Anomalies in tooth morphology were frequently observed with heterozygous patients displaying hypodontia. "

Tooth morphology anomalies are frequent in WNT10A mutation carriers, even in heterozygotes.

Integument 6

Palmoplantar Keratoderma Palmoplantar keratoderma (HP:0000982)

Show evidence (1 reference)

PMID:19559398 SUPPORT Human Clinical

"Odonto-onycho-dermal dysplasia (OODD), a rare autosomal-recessive inherited form of ectodermal dysplasia including severe oligodontia, nail dystrophy, palmoplantar hyperkeratosis, and hyperhidrosis "

Palmoplantar hyperkeratosis is listed as a cardinal feature of OODD.

Dry Skin FREQUENT Dry skin (HP:0000958)

Show evidence (1 reference)

PMID:26964878 SUPPORT Human Clinical

"severe oligodontia, onychodysplasia, palmoplantar hyperkeratosis, dry skin, hypotrichosis, and hyperhidrosis of the palms and soles "

Dry skin is listed among the defining features of OODD.

Hyperkeratosis FREQUENT Hyperkeratosis (HP:0000962)

Show evidence (1 reference)

PMID:17847007 SUPPORT Human Clinical

"hyperkeratosis of the skin "

Hyperkeratosis of the skin is a presenting feature of OODD.

Nail Dystrophy Nail dystrophy (HP:0008404)

Show evidence (1 reference)

PMID:19471313 SUPPORT Human Clinical

"a rare syndrome characterised by severe hypodontia, nail dystrophy, smooth tongue, dry skin, keratoderma and hyperhydrosis of palms and soles "

Nail dystrophy is a defining feature of OODD.

Sparse Hair FREQUENT Sparse hair (HP:0008070)

Show evidence (2 references)

PMID:17847007 SUPPORT Human Clinical

"dry hair "

Dry hair is a presenting feature of OODD. Sparse/dry hair reflects ectodermal appendage involvement.

PMID:26964878 SUPPORT Human Clinical

"hypotrichosis "

Hypotrichosis (sparse hair) is listed among defining OODD features.

Skin Neoplasm Risk Neoplasm of the skin (HP:0008069)

Show evidence (1 reference)

PMID:19559398 SUPPORT Human Clinical

"Schöpf-Schulz-Passarge syndrome, which is so far considered a unique entity by the findings of numerous cysts along eyelid margins and the increased risk of benign and malignant skin tumors "

Skin tumor risk is a characteristic feature distinguishing SSPS from other WNT10A-related ectodermal dysplasias.

Other 4

Selective Tooth Agenesis Selective tooth agenesis (HP:0001592)

Show evidence (1 reference)

PMID:22581971 SUPPORT Human Clinical

"The authors identified WNT10A as a major gene in the aetiology of isolated hypodontia. By including WNT10A in the DNA diagnostics of isolated tooth agenesis, the yield of molecular testing in this condition was significantly increased from 15% to 71%. "

Establishes WNT10A as the most commonly mutated gene in isolated tooth agenesis, increasing diagnostic yield dramatically.

Smooth Tongue FREQUENT Smooth tongue (HP:0010298)

Show evidence (1 reference)

PMID:17847007 SUPPORT Human Clinical

"smooth tongue with marked reduction of fungiform and filiform papillae "

Smooth tongue is listed as a presenting phenotype in the original OODD description.

Palmoplantar Hyperhidrosis FREQUENT Palmoplantar hyperhidrosis (HP:0007410)

Show evidence (1 reference)

PMID:17847007 SUPPORT Human Clinical

"keratoderma and hyperhidrosis of palms and soles "

Hyperhidrosis of palms and soles is a presenting feature of OODD.

Eyelid Apocrine Hidrocystomas Apocrine hidrocystoma (HP:0031454)

Show evidence (2 references)

PMID:19559398 SUPPORT Human Clinical

"Schöpf-Schulz-Passarge syndrome, which is so far considered a unique entity by the findings of numerous cysts along eyelid margins and the increased risk of benign and malignant skin tumors "

Eyelid margin cysts (apocrine hidrocystomas) are the hallmark feature distinguishing SSPS from other WNT10A-related ectodermal dysplasias.

PMID:21834823 SUPPORT Human Clinical

"Schöpf-Schulz-Passarge syndrome (SSPS; MIM224750) is a rare autosomal recessive form of ectodermal dysplasia that was recently shown to result from mutations in the WNT10A gene. "

Confirms that SSPS is caused by WNT10A mutations, establishing molecular overlap with OODD.

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Genetic Associations

1

WNT10A pathogenic variants

Autosomal recessive

Show evidence (4 references)

PMID:17847007 SUPPORT Human Clinical

"Screening of candidate genes in this region led us to identify the same c.697G-->T (p.Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in all patients. "

Original identification of WNT10A as the causative gene for OODD.

PMID:19559398 SUPPORT Human Clinical

"about half of the heterozygotes (53.8%) show a phenotype manifestation, including mainly tooth and nail anomalies, which was not reported before in OODD "

Establishes semi-dominant inheritance with 53.8% penetrance in heterozygous carriers.

PMID:19559398 SUPPORT Human Clinical

"heterozygotes show a sex-biased manifestation pattern, with a significantly higher proportion of tooth anomalies in males than in females, which may implicate gender-specific differences of WNT10A expression "

Identifies sex-biased penetrance in heterozygous WNT10A carriers.

+ 1 more reference

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Treatments

4

Dental Prosthetics and Implants

Action: dental implantation MAXO:0001534

Prosthetic rehabilitation is the mainstay of treatment for oligodontia. Options include removable dentures, fixed bridges, and dental implants (after skeletal maturity).

Show evidence (1 reference)

PMID:26964878 SUPPORT Human Clinical

"dental examination revealed agenesis of permanent teeth except the two maxillary central incisors "

Near-complete absence of permanent teeth establishes the clinical indication for dental prosthetic rehabilitation in OODD.

Supportive Dermatologic Care

Action: supportive care MAXO:0000950

Emollient application for xerosis (urea-based creams), keratolytic agents (salicylic acid 6–10%) for palmoplantar keratoderma, and monitoring of skin lesions. Palmoplantar hyperhidrosis is managed with topical aluminum chloride hexahydrate (20%) as first-line therapy; iontophoresis or botulinum toxin A injections are alternatives for refractory cases. Skin manifestations may be misdiagnosed as psoriasis and require appropriate ectodermal dysplasia-specific management.

Show evidence (1 reference)

PMID:26964878 SUPPORT Human Clinical

"Odonto-onycho-dermal dysplasia (OODD) is a rare form of ectodermal dysplasia characterized by severe oligodontia, onychodysplasia, palmoplantar hyperkeratosis, dry skin, hypotrichosis, and hyperhidrosis of the palms and soles. "

Multiple skin and appendage abnormalities in OODD require ongoing supportive dermatologic care including emollients and keratolytics.

Genetic Counseling

Action: genetic counseling MAXO:0000079

Recommended for affected families given autosomal recessive inheritance and the high carrier frequency of WNT10A pathogenic variants in European populations.

Show evidence (1 reference)

PMID:19559398 SUPPORT Human Clinical

"about half of the heterozygotes (53.8%) show a phenotype manifestation, including mainly tooth and nail anomalies "

High heterozygote penetrance supports genetic counseling for families, as carriers may also be affected.

Ophthalmology Surveillance and Hidrocystoma Management

Action: supportive care MAXO:0000950

Patients with Schöpf-Schulz-Passarge syndrome (SSPS) require ophthalmology evaluation for multiple eyelid apocrine hidrocystomas and surveillance for benign and malignant skin adnexal tumors. Symptomatic hidrocystomas can be managed by CO₂ laser ablation or surgical excision. Annual ophthalmologic review is advisable given the progressive nature of eyelid lesions and elevated risk of adnexal malignancy.

Show evidence (1 reference)

PMID:19559398 SUPPORT Human Clinical

"Schöpf-Schulz-Passarge syndrome, which is so far considered a unique entity by the findings of numerous cysts along eyelid margins and the increased risk of benign and malignant skin tumors "

Eyelid hidrocystomas and elevated skin tumor risk in SSPS establish the need for ophthalmology surveillance and lesion management.

{ }

Source YAML

click to show

name: Odonto-Onycho-Dermal Dysplasia
creation_date: '2026-04-24T12:00:00Z'
updated_date: '2026-04-24T18:30:00Z'
category: Mendelian
description: >-
  Odonto-onycho-dermal dysplasia (OODD) is an autosomal recessive ectodermal
  dysplasia caused by biallelic loss-of-function mutations in WNT10A, encoding
  a ligand in the canonical WNT/beta-catenin signaling pathway. WNT10A is the
  most commonly mutated gene in isolated and syndromic tooth agenesis.
  The phenotypic spectrum ranges from selective tooth agenesis (the mildest
  presentation, often seen in heterozygous carriers) through OODD
  (oligodontia with nail, skin, and palmoplantar keratoderma features) to
  Schopf-Schulz-Passarge syndrome (which adds eyelid apocrine hidrocystomas).
  All three conditions represent a severity continuum of the same WNT10A
  deficiency. The WNT10A c.682T>A (p.Phe228Ile) founder variant is the most
  frequent pathogenic allele in European populations.
disease_term:
  preferred_term: odonto-onycho-dermal dysplasia
  term:
    id: MONDO:0009773
    label: odonto-onycho-dermal dysplasia
parents:
- Ectodermal Dysplasia
- Genetic Disease
has_subtypes:
- name: OODD
  display_name: Odonto-Onycho-Dermal Dysplasia (Classic)
  description: >
    Classic autosomal recessive presentation with severe oligodontia or
    anodontia, onychodysplasia, palmoplantar keratoderma, hyperhidrosis of
    palms and soles, and dry sparse hair. Caused by biallelic WNT10A
    loss-of-function mutations.
  evidence:
  - reference: PMID:17847007
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome
      in which the presenting phenotype is dry hair, severe hypodontia,
      smooth tongue with marked reduction of fungiform and filiform papillae,
      onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and
      hyperkeratosis of the skin.
    explanation: >
      Defines the cardinal features of OODD including dental, nail, skin,
      and hair abnormalities.
- name: SSPS
  display_name: Schopf-Schulz-Passarge Syndrome
  subtype_term:
    preferred_term: Schopf-Schulz-Passarge syndrome
    term:
      id: MONDO:0009145
      label: Schöpf-Schulz-Passarge syndrome
  description: >
    The most severe end of the WNT10A spectrum. Includes all features of OODD
    plus multiple eyelid apocrine hidrocystomas (cysts). Also autosomal
    recessive with biallelic WNT10A mutations.
  evidence:
  - reference: PMID:19559398
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      WNT10A mutations cause not only OODD but also other forms of ectodermal
      dysplasia, reaching from apparently monosymptomatic severe oligodontia
      to Schöpf-Schulz-Passarge syndrome, which is so far considered a
      unique entity by the findings of numerous cysts along eyelid margins
      and the increased risk of benign and malignant skin tumors
    explanation: >
      Demonstrates that SSPS is part of the WNT10A mutation spectrum,
      distinguished by eyelid margin cysts and skin tumor risk.
  - reference: PMID:24398796
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      We conclude that OODD and SSPS should be considered as variable
      expressions of the same WNT10A genotype.
    explanation: >
      Confirms that OODD and SSPS are phenotypic variants of the same
      molecular cause rather than distinct genetic entities.
- name: STHAG4
  display_name: Selective Tooth Agenesis Type 4
  subtype_term:
    preferred_term: selective tooth agenesis type 4
    term:
      id: MONDO:0007881
      label: tooth agenesis, selective, 4
  description: >
    The mildest phenotype in the WNT10A spectrum. Heterozygous (monoallelic)
    WNT10A mutations cause isolated tooth agenesis, most commonly affecting
    mandibular second premolars and maxillary lateral incisors. Autosomal
    dominant inheritance with variable expressivity.
  evidence:
  - reference: PMID:22581971
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      WNT10A mutations were identified in 56% of the cases with non-syndromic
      hypodontia. MSX1, PAX9 and AXIN2 mutations were present in 3%, 9% and
      3% of the cases, respectively.
    explanation: >
      Demonstrates that WNT10A is the most commonly mutated gene in isolated
      hypodontia, responsible for more than half of cases.
pathophysiology:
- name: WNT10A Loss of Function
  description: >
    WNT10A encodes a secreted glycoprotein ligand of the canonical WNT
    signaling pathway. Loss-of-function mutations abolish WNT10A binding
    to Frizzled receptors, preventing activation of the beta-catenin
    destruction complex inhibition and downstream TCF/LEF-mediated
    transcription. This disrupts ectodermal appendage morphogenesis
    including teeth, hair follicles, nails, and sweat glands.
  cell_types:
  - preferred_term: ectodermal cell
    term:
      id: CL:0000221
      label: ectodermal cell
  - preferred_term: ameloblast
    term:
      id: CL:0000059
      label: ameloblast
  - preferred_term: odontoblast
    term:
      id: CL:0000060
      label: odontoblast
  biological_processes:
  - preferred_term: canonical Wnt signaling pathway
    term:
      id: GO:0060070
      label: canonical Wnt signaling pathway
  - preferred_term: odontogenesis
    term:
      id: GO:0042476
      label: odontogenesis
    modifier: DECREASED
  - preferred_term: hair follicle development
    term:
      id: GO:0001942
      label: hair follicle development
    modifier: DECREASED
  downstream:
  - target: Ectodermal Appendage Defects
  evidence:
  - reference: PMID:17847007
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      This is the first report to our knowledge of a human phenotype
      resulting from a mutation in WNT10A, and it is the first demonstration
      of an ectodermal dysplasia caused by an altered WNT signaling pathway,
      expanding the list of WNT-related diseases.
    explanation: >
      Establishes WNT10A as the causative gene for OODD and links
      WNT signaling disruption to ectodermal dysplasia.
  - reference: PMID:19471313
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      WNT10A is expressed in the skin and epidermis and it has shown to be
      critical for the development of ectodermal appendages.
    explanation: >
      Confirms WNT10A expression in skin/epidermis and its critical
      role in ectodermal appendage development.
  - reference: PMID:28105635
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      WNT10A gene encodes a canonical wingless pathway signaling molecule
      involved in cell fate specification as well as morphogenetic patterning
      of the developing ectoderm, nervous system, skeleton, and tooth.
    explanation: >
      Confirms WNT10A role in canonical Wnt pathway and morphogenetic
      patterning of ectoderm and tooth.
- name: Ectodermal Appendage Defects
  description: >
    Disrupted WNT/beta-catenin signaling during embryonic development leads
    to hypoplasia or aplasia of ectodermal appendages. Teeth are most
    severely affected (oligodontia/anodontia), followed by nails
    (dystrophy, thinning), hair (sparse, dry), and sweat glands
    (hypohidrosis or paradoxical hyperhidrosis of palms/soles).
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  biological_processes:
  - preferred_term: ectodermal placode formation
    term:
      id: GO:0060788
      label: ectodermal placode formation
    modifier: DECREASED
  - preferred_term: epidermis development
    term:
      id: GO:0008544
      label: epidermis development
  evidence:
  - reference: PMID:26964878
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Odonto-onycho-dermal dysplasia (OODD) is a rare form of ectodermal
      dysplasia characterized by severe oligodontia, onychodysplasia,
      palmoplantar hyperkeratosis, dry skin, hypotrichosis, and
      hyperhidrosis of the palms and soles.
    explanation: >
      Summarizes the spectrum of ectodermal appendage defects seen in OODD
      including teeth, nails, skin, and hair.
phenotypes:
- category: Dental
  name: Oligodontia
  frequency: VERY_FREQUENT
  description: >
    Absence of six or more permanent teeth is the hallmark feature,
    present in virtually all homozygous/compound heterozygous patients.
    Commonly affects mandibular second premolars, maxillary lateral
    incisors, and lower incisors.
  phenotype_term:
    preferred_term: Oligodontia
    term:
      id: HP:0000677
      label: Oligodontia
  evidence:
  - reference: PMID:28105635
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Mild to severe oligodontia was observed in all patients bearing
      biallelic WNT10A mutations.
    explanation: >
      Demonstrates that oligodontia is universal in biallelic WNT10A
      mutation carriers in a 41-patient cohort.
  - reference: PMID:24700731
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Patients with bi-allelic WNT10A mutations have severe tooth agenesis
      while heterozygous individuals are either unaffected or have a mild
      phenotype.
    explanation: >
      Confirms genotype-phenotype correlation between biallelic mutations
      and severe tooth agenesis.
- category: Dental
  name: Selective Tooth Agenesis
  description: >
    Congenital absence of one or more teeth, the mildest dental phenotype
    seen especially in heterozygous carriers of WNT10A mutations.
  phenotype_term:
    preferred_term: Selective tooth agenesis
    term:
      id: HP:0001592
      label: Selective tooth agenesis
  subtype: STHAG4
  evidence:
  - reference: PMID:22581971
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      The authors identified WNT10A as a major gene in the aetiology of
      isolated hypodontia. By including WNT10A in the DNA diagnostics of
      isolated tooth agenesis, the yield of molecular testing in this
      condition was significantly increased from 15% to 71%.
    explanation: >
      Establishes WNT10A as the most commonly mutated gene in isolated
      tooth agenesis, increasing diagnostic yield dramatically.
- category: Dental
  name: Smooth Tongue
  frequency: FREQUENT
  description: >
    Smooth tongue with marked reduction of fungiform and filiform papillae,
    reflecting ectodermal involvement in tongue surface differentiation.
  phenotype_term:
    preferred_term: Smooth tongue
    term:
      id: HP:0010298
      label: Smooth tongue
  evidence:
  - reference: PMID:17847007
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      smooth tongue with marked reduction of fungiform and filiform papillae
    explanation: >
      Smooth tongue is listed as a presenting phenotype in the original
      OODD description.
- category: Dermatological
  name: Palmoplantar Keratoderma
  description: >
    Thickened, hyperkeratotic skin on palms and soles, often with a
    smooth waxy texture. A cardinal feature of OODD and SSPS.
  phenotype_term:
    preferred_term: Palmoplantar keratoderma
    term:
      id: HP:0000982
      label: Palmoplantar keratoderma
  evidence:
  - reference: PMID:19559398
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Odonto-onycho-dermal dysplasia (OODD), a rare autosomal-recessive
      inherited form of ectodermal dysplasia including severe oligodontia,
      nail dystrophy, palmoplantar hyperkeratosis, and hyperhidrosis
    explanation: >
      Palmoplantar hyperkeratosis is listed as a cardinal feature of OODD.
- category: Dermatological
  name: Palmoplantar Hyperhidrosis
  frequency: FREQUENT
  description: >
    Excessive sweating localized to palms and soles, paradoxically
    co-occurring with dry skin elsewhere.
  phenotype_term:
    preferred_term: Palmoplantar hyperhidrosis
    term:
      id: HP:0007410
      label: Palmoplantar hyperhidrosis
  evidence:
  - reference: PMID:17847007
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      keratoderma and hyperhidrosis of palms and soles
    explanation: >
      Hyperhidrosis of palms and soles is a presenting feature of OODD.
- category: Dermatological
  name: Dry Skin
  frequency: FREQUENT
  description: >
    Generalized dry skin (xerosis) reflecting ectodermal involvement
    beyond palmoplantar surfaces.
  phenotype_term:
    preferred_term: Dry skin
    term:
      id: HP:0000958
      label: Dry skin
  evidence:
  - reference: PMID:26964878
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      severe oligodontia, onychodysplasia, palmoplantar hyperkeratosis,
      dry skin, hypotrichosis, and hyperhidrosis of the palms and soles
    explanation: >
      Dry skin is listed among the defining features of OODD.
- category: Dermatological
  name: Hyperkeratosis
  frequency: FREQUENT
  description: >
    Generalized hyperkeratosis of the skin beyond palmoplantar surfaces.
  phenotype_term:
    preferred_term: Hyperkeratosis
    term:
      id: HP:0000962
      label: Hyperkeratosis
  evidence:
  - reference: PMID:17847007
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      hyperkeratosis of the skin
    explanation: >
      Hyperkeratosis of the skin is a presenting feature of OODD.
- category: Nail
  name: Nail Dystrophy
  description: >
    Nail abnormalities including thinning, ridging, brittleness, and
    slow growth affecting fingernails and toenails.
  phenotype_term:
    preferred_term: Nail dystrophy
    term:
      id: HP:0008404
      label: Nail dystrophy
  evidence:
  - reference: PMID:19471313
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      a rare syndrome characterised by severe hypodontia, nail dystrophy,
      smooth tongue, dry skin, keratoderma and hyperhydrosis of palms and
      soles
    explanation: >
      Nail dystrophy is a defining feature of OODD.
- category: Hair
  name: Sparse Hair
  frequency: FREQUENT
  description: >
    Thin, dry, and sparse scalp hair. Body hair may also be reduced.
  phenotype_term:
    preferred_term: Sparse hair
    term:
      id: HP:0008070
      label: Sparse hair
  evidence:
  - reference: PMID:17847007
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      dry hair
    explanation: >
      Dry hair is a presenting feature of OODD. Sparse/dry hair reflects
      ectodermal appendage involvement.
  - reference: PMID:26964878
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      hypotrichosis
    explanation: >
      Hypotrichosis (sparse hair) is listed among defining OODD features.
- category: Ophthalmological
  name: Eyelid Apocrine Hidrocystomas
  description: >
    Multiple apocrine hidrocystomas of the eyelids, distinguishing
    Schopf-Schulz-Passarge syndrome from classic OODD.
  phenotype_term:
    preferred_term: Apocrine hidrocystoma
    term:
      id: HP:0031454
      label: Apocrine hidrocystoma
  subtype: SSPS
  evidence:
  - reference: PMID:19559398
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Schöpf-Schulz-Passarge syndrome, which is so far considered a unique
      entity by the findings of numerous cysts along eyelid margins and the
      increased risk of benign and malignant skin tumors
    explanation: >
      Eyelid margin cysts (apocrine hidrocystomas) are the hallmark feature
      distinguishing SSPS from other WNT10A-related ectodermal dysplasias.
  - reference: PMID:21834823
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Schöpf-Schulz-Passarge syndrome (SSPS; MIM224750) is a rare autosomal
      recessive form of ectodermal dysplasia that was recently shown to
      result from mutations in the WNT10A gene.
    explanation: >
      Confirms that SSPS is caused by WNT10A mutations, establishing
      molecular overlap with OODD.
- category: Dermatological
  name: Skin Neoplasm Risk
  description: >
    Increased risk of benign and malignant skin tumors, a distinguishing
    feature of Schopf-Schulz-Passarge syndrome within the WNT10A spectrum.
  phenotype_term:
    preferred_term: Neoplasm of the skin
    term:
      id: HP:0008069
      label: Neoplasm of the skin
  subtype: SSPS
  evidence:
  - reference: PMID:19559398
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Schöpf-Schulz-Passarge syndrome, which is so far considered a unique
      entity by the findings of numerous cysts along eyelid margins and the
      increased risk of benign and malignant skin tumors
    explanation: >
      Skin tumor risk is a characteristic feature distinguishing SSPS from
      other WNT10A-related ectodermal dysplasias.
- category: Dental
  name: Abnormal Tooth Morphology
  frequency: FREQUENT
  description: >
    Teeth that are present may show morphological abnormalities including
    microdontia, peg-shaped teeth, or enamel defects.
  phenotype_term:
    preferred_term: Abnormal dental morphology
    term:
      id: HP:0006482
      label: Abnormal dental morphology
  evidence:
  - reference: PMID:28105635
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Anomalies in tooth morphology were frequently observed with
      heterozygous patients displaying hypodontia.
    explanation: >
      Tooth morphology anomalies are frequent in WNT10A mutation carriers,
      even in heterozygotes.
genetic:
- name: WNT10A pathogenic variants
  inheritance:
  - name: Autosomal recessive
    evidence:
    - reference: PMID:17847007
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >
        Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome
      explanation: >
        Establishes autosomal recessive inheritance for OODD.
  variants:
  - name: c.697G>T (p.Glu233X)
    description: >
      First identified pathogenic WNT10A variant. Homozygous nonsense
      mutation found in consanguineous Lebanese families with OODD.
      Predicted to cause premature truncation at 232 of 417 amino acids.
    evidence:
    - reference: PMID:17847007
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >
        Screening of candidate genes in this region led us to identify the
        same c.697G-->T (p.Glu233X) homozygous nonsense mutation in exon 3
        of the WNT10A gene in all patients.
      explanation: >
        Identifies the first pathogenic WNT10A mutation causing OODD.
  - name: c.682T>A (p.Phe228Ile)
    description: >
      Most common pathogenic WNT10A allele in European populations.
      Allele frequency approximately 10 times higher in tooth agenesis
      cohorts than in general population databases.
    evidence:
    - reference: PMID:24700731
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >
        The WNT10A Phe228Ile variant alone reached an allele frequency of
        0.21 in the tooth agenesis cohort, about 10 times higher than the
        allele frequency reported in large SNP databases for Caucasian
        populations.
      explanation: >
        Quantifies the enrichment of the Phe228Ile founder variant in
        tooth agenesis patients relative to the general population.
  - name: c.392C>T (p.Ala131Val)
    description: >
      Missense mutation in a conserved alpha-helix domain of WNT10A.
      Identified in a consanguineous Pakistani family with complete OODD.
    evidence:
    - reference: PMID:19471313
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >
        a homozygous c.392C>T transition in exon 3 of WNT10A, which
        predicts a p.A131V substitution in a conserved alpha-helix domain
      explanation: >
        First inherited missense mutation reported in WNT10A causing OODD.
  - name: c.321C>A (p.Cys107X)
    description: >
      Nonsense mutation reported in both OODD and SSPS, illustrating
      allelic heterogeneity and phenotypic variability with the same
      mutation.
    evidence:
    - reference: PMID:21834823
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >
        a 59-year-old woman with SSPS in whom a homozygous nonsense
        mutation (p.Cys107X) in WNT10A was detected
      explanation: >
        Same p.Cys107X mutation causes SSPS, demonstrating phenotypic
        variability within the WNT10A spectrum.
  notes: >
    About half of heterozygous carriers (53.8%) show phenotypic manifestations,
    primarily tooth and nail anomalies, with a sex-biased pattern showing
    significantly higher penetrance in males. WNT10A mutations are found in
    approximately 9% of unselected ectodermal dysplasia patients and cause
    35-50% of selective tooth agenesis cases.
  evidence:
  - reference: PMID:17847007
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Screening of candidate genes in this region led us to identify the
      same c.697G-->T (p.Glu233X) homozygous nonsense mutation in exon 3
      of the WNT10A gene in all patients.
    explanation: >
      Original identification of WNT10A as the causative gene for OODD.
  - reference: PMID:19559398
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      about half of the heterozygotes (53.8%) show a phenotype
      manifestation, including mainly tooth and nail anomalies, which was
      not reported before in OODD
    explanation: >
      Establishes semi-dominant inheritance with 53.8% penetrance in
      heterozygous carriers.
  - reference: PMID:19559398
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      heterozygotes show a sex-biased manifestation pattern, with a
      significantly higher proportion of tooth anomalies in males than
      in females, which may implicate gender-specific differences of
      WNT10A expression
    explanation: >
      Identifies sex-biased penetrance in heterozygous WNT10A carriers.
  - reference: PMID:24700731
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Mutations in the WNT10A gene were first detected in the rare
      syndrome odonto-onycho-dermal dysplasia (OODD, OMIM257980) but have
      now also been found to cause about 35-50% of selective tooth
      agenesis (STHAG4, OMIM150400)
    explanation: >
      WNT10A mutations account for 35-50% of selective tooth agenesis.
treatments:
- name: Dental Prosthetics and Implants
  description: >
    Prosthetic rehabilitation is the mainstay of treatment for
    oligodontia. Options include removable dentures, fixed bridges,
    and dental implants (after skeletal maturity).
  treatment_term:
    preferred_term: dental implantation
    term:
      id: MAXO:0001534
      label: dental implantation
  evidence:
  - reference: PMID:26964878
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      dental examination revealed agenesis of permanent teeth except the
      two maxillary central incisors
    explanation: >
      Near-complete absence of permanent teeth establishes the clinical
      indication for dental prosthetic rehabilitation in OODD.
- name: Supportive Dermatologic Care
  description: >
    Emollient application for xerosis (urea-based creams), keratolytic agents
    (salicylic acid 6–10%) for palmoplantar keratoderma, and monitoring of skin
    lesions. Palmoplantar hyperhidrosis is managed with topical aluminum chloride
    hexahydrate (20%) as first-line therapy; iontophoresis or botulinum toxin A
    injections are alternatives for refractory cases. Skin manifestations may be
    misdiagnosed as psoriasis and require appropriate ectodermal dysplasia-specific
    management.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:26964878
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Odonto-onycho-dermal dysplasia (OODD) is a rare form of ectodermal
      dysplasia characterized by severe oligodontia, onychodysplasia,
      palmoplantar hyperkeratosis, dry skin, hypotrichosis, and
      hyperhidrosis of the palms and soles.
    explanation: >
      Multiple skin and appendage abnormalities in OODD require ongoing
      supportive dermatologic care including emollients and keratolytics.
- name: Genetic Counseling
  description: >
    Recommended for affected families given autosomal recessive
    inheritance and the high carrier frequency of WNT10A pathogenic
    variants in European populations.
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
  evidence:
  - reference: PMID:19559398
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      about half of the heterozygotes (53.8%) show a phenotype
      manifestation, including mainly tooth and nail anomalies
    explanation: >
      High heterozygote penetrance supports genetic counseling for families,
      as carriers may also be affected.
- name: Ophthalmology Surveillance and Hidrocystoma Management
  description: >
    Patients with Schöpf-Schulz-Passarge syndrome (SSPS) require ophthalmology
    evaluation for multiple eyelid apocrine hidrocystomas and surveillance for
    benign and malignant skin adnexal tumors. Symptomatic hidrocystomas can be
    managed by CO₂ laser ablation or surgical excision. Annual ophthalmologic
    review is advisable given the progressive nature of eyelid lesions and elevated
    risk of adnexal malignancy.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:19559398
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Schöpf-Schulz-Passarge syndrome, which is so far considered a unique
      entity by the findings of numerous cysts along eyelid margins and the
      increased risk of benign and malignant skin tumors
    explanation: >
      Eyelid hidrocystomas and elevated skin tumor risk in SSPS establish
      the need for ophthalmology surveillance and lesion management.
histopathology:
- name: Eccrine Syringofibroadenomatosis
  description: >
    Skin biopsies from hyperkeratotic palms and soles show characteristic
    changes of eccrine syringofibroadenomatosis, a histopathological
    finding described in patients with ectodermal dysplasias.
  finding_term:
    preferred_term: Eccrine syringofibroadenoma
    term:
      id: NCIT:C43356
      label: Syringofibroadenoma
  evidence:
  - reference: PMID:26964878
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Skin biopsies from the hyperkeratotic palms and soles showed the
      characteristic changes of eccrine syringofibroadenomatosis, which
      has been described in patients with ectodermal dysplasias.
    explanation: >
      Documents eccrine syringofibroadenomatosis as a characteristic
      histopathological finding in OODD skin biopsies.
diagnosis:
- name: Clinical Diagnosis
  description: >
    Diagnosis based on the combination of severe oligodontia,
    onychodysplasia, palmoplantar keratoderma, and hyperhidrosis. Dental
    radiograph (OPG) documents tooth agenesis pattern; dermatological
    assessment quantifies PPK severity. The condition can be difficult to
    diagnose as individual features may be misattributed to common conditions
    such as psoriasis. Interdisciplinary evaluation (dentistry, dermatology,
    ophthalmology for SSPS) is essential.
  evidence:
  - reference: PMID:26964878
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      This case illustrates the challenges of diagnosing ectodermal
      dysplasia like OODD and highlights the relevance of interdisciplinary
      cooperation in the diagnosis of rare conditions.
    explanation: >
      Emphasizes the need for interdisciplinary evaluation for diagnosis.
- name: WNT10A Molecular Genetic Testing
  description: >
    Molecular confirmation via WNT10A sequencing (full coding region and splice
    sites) is the gold standard. WNT10A is identified in more than half of cases
    with isolated hypodontia and is found in approximately 9% of unselected
    ectodermal dysplasia patients. Including WNT10A in dental agenesis panels
    dramatically improves the diagnostic yield. For oligodontia with ectodermal
    features, a gene panel covering WNT10A alongside EDA, EDAR, EDARADD, MSX1,
    and PAX9 is recommended.
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: MAXO:0000533
      label: molecular genetic testing
  evidence:
  - reference: PMID:22581971
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      By including WNT10A in the DNA diagnostics of isolated tooth agenesis,
      the yield of molecular testing in this condition was significantly
      increased from 15% to 71%.
    explanation: >
      Adding WNT10A to molecular testing panels dramatically improves
      diagnostic yield in tooth agenesis from 15% to 71%.
  - reference: PMID:28105635
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      Mild to severe oligodontia was observed in all patients bearing
      biallelic WNT10A mutations.
    explanation: >
      Universal oligodontia in biallelic WNT10A mutation carriers makes
      molecular testing essential when severe tooth agenesis is present.
- name: Differential Diagnosis from Hypohidrotic Ectodermal Dysplasia
  description: >
    WNT10A-related ectodermal dysplasia must be distinguished from
    EDA1/EDAR/EDARADD-related hypohidrotic/anhidrotic ectodermal dysplasia
    (HED/EDA). Key distinguishing features: WNT10A patients show a marked dental
    phenotype and absent or minimal facial dysmorphism (no frontal bossing, no
    saddle nose), whereas EDA1-related HED typically features frontal bossing,
    saddle nose, and periorbital hyperpigmentation. Together, EDA1, EDAR,
    EDARADD, and WNT10A account for approximately 90% of HED/EDA cases.
  evidence:
  - reference: PMID:20979233
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >
      patients harboring WNT10A mutations displayed distinctive clinical
      features (marked dental phenotype, no facial dysmorphism), helping to
      decide which gene should be first investigated in HED/EDA.
    explanation: >
      WNT10A-related ectodermal dysplasia can be distinguished from EDA1/EDAR-related
      HED by predominant dental involvement and absence of facial dysmorphism.
inheritance:
- name: Autosomal recessive
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >
    OODD and SSPS follow autosomal recessive inheritance. However,
    heterozygous carriers frequently manifest tooth agenesis and mild
    ectodermal features (semi-dominant with variable penetrance), making
    WNT10A one of the few ectodermal dysplasia genes with significant
    heterozygote phenotypic effects.
datasets: []

📚

References & Deep Research

Deep Research

1

Falcon ▸

1. Disease Information

Edison Scientific Literature 22 citations 2026-04-24T18:28:17.971839

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)

OMIM/MIM disease number: 257980 (OODD) (yu2019distinctimpactsof pages 1-2, bohring2009wnt10amutationsare pages 1-3)
Causal gene: WNT10A (chromosome 2q35) (yu2019distinctimpactsof pages 1-2, kalaszi2026casereportnovel pages 1-2)
OMIM/MIM gene number: WNT10A *606268 (yu2019distinctimpactsof pages 1-2, bohring2009wnt10amutationsare pages 1-3)

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

Clinical manifestations begin during development and are often recognized in childhood (e.g., early dental referral at 23 months in a WNT10A-deficient case). (garciamartinez2023dentalphenotypewith pages 2-6)
In one OODD family description, palmoplantar hyperkeratosis appeared “at around age 3 years,” while growth and mental development were normal. (adaimy2007mutationinwnt10a pages 1-4)

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.

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

WNT10A is the causal gene for OODD. (adaimy2007mutationinwnt10a pages 1-4, bohring2009wnt10amutationsare pages 1-3)

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.

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

Epigenetic mechanisms and chromosomal structural abnormalities were not identified in the retrieved excerpts.
Candidate modifiers suggested by case/cohort data include EDAR (Val370Ala) (garciamartinez2023dentalphenotypewith pages 1-2) and digenic interactions involving EDA with WNT10A (liu2024compoundheterozygouswnt10a pages 1-2).

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

2023: recognition of “dental-dominant” WNT10A deficiency presentations with mild ectodermal signs and possible modifier effects (EDAR Val370Ala) (garciamartinez2023dentalphenotypewith pages 1-2).
2024: evidence supporting digenic/modifier interactions (EDA + WNT10A) affecting tooth agenesis severity, with structural modeling implicating altered WNT10A–FZD5 interactions (liu2024compoundheterozygouswnt10a pages 1-2).

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

(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.
(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.

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Inheritance

Subtypes

Pathophysiology

Histopathology

Pathograph

Phenotypes

Genetic Associations

Treatments

Source YAML

References & Deep Research

Deep Research

1. Disease Information

1.1 Definition and overview

1.2 Key identifiers (as available in retrieved sources)

1.3 Synonyms / alternative names

1.4 Evidence source type

2. Etiology

2.1 Disease causal factors

2.2 Genetic risk factors and genotype–phenotype considerations

2.3 Protective factors

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

3. Phenotypes

3.1 Core phenotype spectrum (current understanding)

3.2 Phenotype frequencies / statistics from available cohorts

3.3 Onset and progression

3.4 Quality of life impacts (as available)

3.5 Suggested HPO mapping

4. Genetic / Molecular Information

4.1 Causal gene

4.2 Pathogenic variants (examples from primary literature)

4.3 Functional consequence (current understanding)

4.4 Epigenetics, chromosomal abnormalities, modifier genes

5. Environmental Information

6. Mechanism / Pathophysiology

6.1 Pathway-level mechanism

6.2 Tissue/cell types implicated (ontology suggestions)

6.3 Protein features relevant to disease

6.4 Model organism evidence

7. Anatomical Structures Affected

7.1 Organ systems

8. Temporal Development

9. Inheritance and Population

9.1 Inheritance

9.2 Population and carrier manifestations

10. Diagnostics

10.1 Clinical and radiographic evaluation

10.2 Genetic testing approaches (real-world implementations)

10.3 Differential diagnosis

11. Outcome / Prognosis

12. Treatment

12.1 Current standard of care

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

12.3 Pharmacotherapy / advanced therapeutics

12.4 Clinical trials

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Mouse models

Key visual evidence

Summary of key 2023–2024 developments

Limitations of this evidence set