Osteoglophonic Dysplasia

Mendelian MONDO:0008150 Pathograph 5 FGFR1-related disorder Skeletal dysplasia

Osteoglophonic dysplasia is a rare skeletal disorder caused by gain-of-function mutations in FGFR1. It is characterized by craniosynostosis, rhizomelic dwarfism, nonossifying fibrous metaphyseal lesions, and severe midface hypoplasia with frontal bossing. The name derives from the Greek for "hollowed-out bone" referring to the characteristic lucent metaphyseal defects visible on radiographs. Like Pfeiffer syndrome, it results from constitutive FGFR1 activation, but produces a distinct phenotype affecting both craniofacial and appendicular skeleton with characteristic fibrous bone lesions.

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1
Inheritance
4
Pathophys.
25
Phenotypes
5
Pathograph
1
Genes
2
Treatments
1
References
1
Deep Research
👪

Inheritance

1
Autosomal dominant HP:0000006
Osteoglophonic dysplasia follows autosomal dominant inheritance with gain-of-function mutations in FGFR1.
Autosomal dominant inheritance
Show evidence (1 reference)
PMID:29019756 SUPPORT Human Clinical
"Most of these mutations are inherited in an autosomal dominant fashion and are gain-of-function-type mutations."
Confirms autosomal dominant GOF inheritance pattern for FGFR-related skeletal disorders.
⚙

Pathophysiology

4
FGFR1 Constitutive Activation
Gain-of-function mutations in FGFR1 cause constitutive receptor activation, leading to overactive FGF signaling in skeletal tissues. This molecular defect drives multiple downstream consequences in both craniofacial and appendicular skeletal development.
Osteoblast link
FGFR signaling pathway link ↑ INCREASED
Downstream
Premature Cranial Suture Fusion
Impaired Endochondral Ossification
Aberrant Fibrous Tissue Formation
Show evidence (1 reference)
PMID:29019756 SUPPORT Human Clinical
"Skeletal disorders caused by type 1 mutations include Pfeiffer syndrome (PS) and osteoglophonic dysplasia"
Confirms osteoglophonic dysplasia is caused by FGFR1 (type 1) mutations.
Premature Cranial Suture Fusion
Constitutive FGFR1 activation drives premature osteoblast differentiation at cranial suture margins, causing premature suture fusion (craniosynostosis) and resulting in abnormal skull shape with frontal bossing and midface hypoplasia.
Cranial suture morphogenesis link
Show evidence (1 reference)
PMID:38648328 SUPPORT Human Clinical
"Osteoglophonic dysplasia (OGD) is characterized by multisuture craniosynostosis (including cloverleaf skull)"
GeneReviews directly identifies multisuture craniosynostosis as a defining manifestation of OGD.
Impaired Endochondral Ossification
FGFR1 overactivation impairs normal endochondral ossification in the growth plates of long bones, leading to rhizomelic (proximal) limb shortening and short stature.
Endochondral ossification link ↓ DECREASED Bone development link ↓ DECREASED
Show evidence (1 reference)
PMID:29019756 SUPPORT Human Clinical
"FGFR1, FGFR2, and FGFR3 are crucial for both chondrogenesis and osteogenesis. Mutations in the genes encoding FGFRs, types 1-3, are responsible for various skeletal dysplasias and craniosynostosis syndromes."
Establishes that FGFR1 mutations disrupt both chondrogenesis and osteogenesis, underlying the endochondral ossification defect.
Aberrant Fibrous Tissue Formation
OGD is characterized by nonossifying fibrous lesions within metaphyseal bone, producing the characteristic radiolucent defects that give the disorder its name ("hollowed-out bone").
Show evidence (1 reference)
PMID:15625620 SUPPORT Human Clinical
"Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder."
White et al. explicitly identify nonossifying bone lesions as a characteristic feature of OGD.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Osteoglophonic Dysplasia Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

25
Ear 1
Low-set ears Low-set ears (HP:0000369)
Show evidence (1 reference)
PMID:38648328 SUPPORT Human Clinical
"distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
GeneReviews includes low-set ears in the characteristic craniofacial phenotype.
Eye 2
Proptosis Proptosis (HP:0000520)
Show evidence (1 reference)
PMID:38648328 SUPPORT Human Clinical
"distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
GeneReviews includes proptosis among the distinctive craniofacial features of OGD.
Hypertelorism Hypertelorism (HP:0000316)
Show evidence (1 reference)
PMID:38648328 SUPPORT Human Clinical
"distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
The GeneReviews summary uses "widely spaced eyes," best represented by the HPO term hypertelorism.
Head and Neck 9
Multisuture craniosynostosis Craniosynostosis (HP:0001363)
Show evidence (1 reference)
PMID:38648328 SUPPORT Human Clinical
"CLINICAL CHARACTERISTICS: Osteoglophonic dysplasia (OGD) is characterized by multisuture craniosynostosis (including cloverleaf skull)"
GeneReviews identifies multisuture craniosynostosis as a defining clinical feature of OGD.
Frontal bossing Frontal bossing (HP:0002007)
Show evidence (1 reference)
PMID:35148738 SUPPORT Human Clinical
"The details of the 4-year follow-up showed that the signs of OD were more pronounced, including dwarfism, frontal bossing, delayed skeletal maturation, anteverted nares, micrognathia, and prominent ears, but the patient's impacted teeth and edentulous jaws remained unchanged."
The 4-year follow-up case directly documents frontal bossing.
Depressed nasal bridge Depressed nasal bridge (HP:0005280)
Show evidence (1 reference)
PMID:15625620 SUPPORT Human Clinical
"Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder."
White et al. describe depressed nasal bridge as part of the characteristic OGD facial phenotype.
Midface retrusion Midface retrusion (HP:0011800)
Show evidence (1 reference)
PMID:38648328 SUPPORT Human Clinical
"distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
GeneReviews includes midface retrusion in the characteristic craniofacial pattern.
Short nose Short nose (HP:0003196)
Show evidence (1 reference)
PMID:38648328 SUPPORT Human Clinical
"distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
Short nose is included in the GeneReviews craniofacial feature summary.
Anteverted nares Anteverted nares (HP:0000463)
Show evidence (1 reference)
PMID:35148738 SUPPORT Human Clinical
"The details of the 4-year follow-up showed that the signs of OD were more pronounced, including dwarfism, frontal bossing, delayed skeletal maturation, anteverted nares, micrognathia, and prominent ears, but the patient's impacted teeth and edentulous jaws remained unchanged."
The 4-year follow-up case directly documents anteverted nares.
High palate High palate (HP:0000218)
Show evidence (1 reference)
PMID:38648328 SUPPORT Human Clinical
"distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
GeneReviews includes high palate in the craniofacial phenotype summary.
Delayed eruption of teeth Delayed eruption of teeth (HP:0000684)
Show evidence (1 reference)
PMID:29147600 SUPPORT Human Clinical
"She presented with disproportionate short stature, craniosynostosis, a prominent supraorbital ridge, delayed teeth eruption, hypodontia, and multiple nonossifying bone lesions in the femur, tibia, and fibula."
The Indian mutation-confirmed case directly documents delayed eruption of teeth.
Hypodontia Hypodontia (HP:0000668)
Show evidence (1 reference)
PMID:29147600 SUPPORT Human Clinical
"Rhizomelic dwarfism, craniosynostosis, impacted teeth, hypodontia or anodontia, and multiple nonossifying bone lesions are the salient features of this condition."
Kuthiroly et al. list hypodontia, sometimes progressing to clinical anodontia, among the salient features of OGD.
Limbs 1
Nonossifying fibromas of the long bones Abnormal metaphysis morphology (HP:0000944)
Show evidence (2 references)
PMID:15625620 SUPPORT Human Clinical
"Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder."
White et al. identify nonossifying bone lesions as characteristic of OGD.
PMID:29147600 SUPPORT Human Clinical
"She presented with disproportionate short stature, craniosynostosis, a prominent supraorbital ridge, delayed teeth eruption, hypodontia, and multiple nonossifying bone lesions in the femur, tibia, and fibula."
The Indian case localizes the lesions to the long bones; HPO lacks a more specific nonossifying fibroma term, so abnormal metaphysis morphology is the closest grounded fit.
Metabolism 1
Hypophosphatemia Hypophosphatemia (HP:0002148)
Show evidence (1 reference)
PMID:40260920 SUPPORT Human Clinical
"Patients may have hypophosphatemia due to high FGF23 levels."
The 2025 OGD update explicitly identifies hypophosphatemia as part of the disease spectrum and links it to elevated FGF23.
Musculoskeletal 4
Platyspondyly Platyspondyly (HP:0000926)
Show evidence (1 reference)
PMID:8995175 SUPPORT Human Clinical
"The appearance and gradual enlargement of fibrous cortical defects and multiple nonossifying fibromata are documented in this report of a 2-year-old boy with a very rare skeletal dysplasia known as osteoglophonic dysplasia, characterized by multiple and recurrent craniosynostoses, platyspondyly,..."
Azouz and Kozlowski document platyspondyly as part of the characteristic radiographic phenotype.
Epiphyseal dysplasia Epiphyseal dysplasia (HP:0002656)
Show evidence (1 reference)
PMID:8995175 SUPPORT Human Clinical
"The appearance and gradual enlargement of fibrous cortical defects and multiple nonossifying fibromata are documented in this report of a 2-year-old boy with a very rare skeletal dysplasia known as osteoglophonic dysplasia, characterized by multiple and recurrent craniosynostoses, platyspondyly,..."
The same radiology report identifies epiphyseal dysplasia as part of the OGD skeletal pattern.
Osteopenia Osteopenia (HP:0000938)
Show evidence (1 reference)
PMID:38648328 SUPPORT Human Clinical
"Radiographs show copper beaten appearance to skull, multiple cystic long bone lesions consistent with non-ossifying fibromas, irregular vertebral bodies, and osteopenia with increased risk of fractures."
GeneReviews includes osteopenia in the characteristic radiographic findings of OGD.
Pathologic fracture Pathologic fracture (HP:0002756)
Show evidence (1 reference)
PMID:8958322 SUPPORT Human Clinical
"Manifestations, not previously reported in osteoglophonic dysplasia, present in the propositus are spontaneous fractures resulting in pseudoarthroses through cystic and dysplastic foci in his proximal femoral shafts and right humerus"
Spontaneous fractures through dysplastic bone are documented as an important, though apparently uncommon, complication.
Growth 2
Disproportionate short-limb short stature Disproportionate short-limb short stature (HP:0008873)
Show evidence (1 reference)
PMID:29147600 SUPPORT Human Clinical
"She presented with disproportionate short stature, craniosynostosis, a prominent supraorbital ridge, delayed teeth eruption, hypodontia, and multiple nonossifying bone lesions in the femur, tibia, and fibula."
The mutation-confirmed Indian case directly documents disproportionate short stature.
Rhizomelia Rhizomelia (HP:0008905)
Show evidence (1 reference)
PMID:15625620 SUPPORT Human Clinical
"Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder."
White et al. describe rhizomelic dwarfism as a characteristic skeletal feature of OGD.
Other 5
Prominent supraorbital ridges Prominent supraorbital ridges (HP:0000336)
Show evidence (1 reference)
PMID:15625620 SUPPORT Human Clinical
"Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder."
White et al. identify prominent supraorbital ridging as a characteristic craniofacial manifestation.
Impacted teeth Impacted tooth (HP:0011079)
Show evidence (1 reference)
PMID:16918680 SUPPORT Human Clinical
"Radiographically, multiple lucent lesions were present in the tubular bones and mandible as well as several impacted teeth."
Roberts et al. directly document multiple impacted teeth in a long-term follow-up case.
Gingival overgrowth Gingival overgrowth (HP:0000212)
Show evidence (1 reference)
PMID:38648328 SUPPORT Human Clinical
"distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
GeneReviews includes gingival overgrowth among the characteristic craniofacial and oral features.
Overlapping toe Overlapping toe (HP:0001845)
Show evidence (1 reference)
PMID:40260920 SUPPORT Human Clinical
"Both showed classic symptoms as well as signs not previously reported, including elevated frontal temperature and overlapping toes."
The 2025 case series expands the phenotype to include overlapping toes.
Prognathism Mandibular prognathia (HP:0000303)
Show evidence (1 reference)
PMID:38648328 SUPPORT Human Clinical
"distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
GeneReviews includes prognathism among the characteristic craniofacial features of OGD.
🧬

Genetic Associations

1
FGFR1 gain-of-function mutations (Causative)
Show evidence (2 references)
PMID:29019756 SUPPORT Human Clinical
"Skeletal disorders caused by type 1 mutations include Pfeiffer syndrome (PS) and osteoglophonic dysplasia"
Confirms FGFR1 mutations cause osteoglophonic dysplasia.
CGGV:assertion_d958e743-2ca0-4bb9-a198-364dd58005c3-2021-03-22T203501.315Z SUPPORT Other
"FGFR1 | HGNC:3688 | osteoglophonic dwarfism | MONDO:0008150 | AD | Limited"
ClinGen classifies the FGFR1-osteoglophonic dwarfism gene-disease relationship as limited with autosomal dominant inheritance.
💊

Treatments

2
Orthopedic management
Action: Orthopedic management Ontology label: surgical procedure MAXO:0000004
Orthopedic management of skeletal complications including rhizomelic dwarfism and fibrous bone lesions. Surgical intervention may be required for severe limb deformities.
Craniofacial surgery
Action: Craniofacial surgery Ontology label: surgical procedure MAXO:0000004
Surgical correction of craniosynostosis and midface hypoplasia as needed.
{ }

Source YAML

click to show 
name: Osteoglophonic Dysplasia
creation_date: '2026-04-04T12:00:00Z'
updated_date: '2026-04-19T21:32:38Z'
category: Mendelian
description: >-
  Osteoglophonic dysplasia is a rare skeletal disorder caused by gain-of-function mutations
  in FGFR1. It is characterized by craniosynostosis, rhizomelic dwarfism, nonossifying
  fibrous metaphyseal lesions, and severe midface hypoplasia with frontal bossing. The name
  derives from the Greek for "hollowed-out bone" referring to the characteristic lucent
  metaphyseal defects visible on radiographs. Like Pfeiffer syndrome, it results from
  constitutive FGFR1 activation, but produces a distinct phenotype affecting both
  craniofacial and appendicular skeleton with characteristic fibrous bone lesions.
disease_term:
  preferred_term: osteoglophonic dysplasia
  term:
    id: MONDO:0008150
    label: osteoglophonic dysplasia
parents:
- FGFR1-related disorder
- Skeletal dysplasia
inheritance:
- name: Autosomal dominant
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  description: >-
    Osteoglophonic dysplasia follows autosomal dominant inheritance with
    gain-of-function mutations in FGFR1.
  evidence:
  - reference: PMID:29019756
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Most of these mutations are inherited in an autosomal dominant fashion and are gain-of-function-type mutations."
    explanation: Confirms autosomal dominant GOF inheritance pattern for FGFR-related skeletal disorders.
pathophysiology:
- name: FGFR1 Constitutive Activation
  description: >-
    Gain-of-function mutations in FGFR1 cause constitutive receptor activation,
    leading to overactive FGF signaling in skeletal tissues. This molecular defect
    drives multiple downstream consequences in both craniofacial and appendicular
    skeletal development.
  gene:
    preferred_term: FGFR1
    description: Fibroblast growth factor receptor 1, constitutively activated by gain-of-function mutations in osteoglophonic dysplasia.
    modifier: INCREASED
    term:
      id: hgnc:3688
      label: FGFR1
  cell_types:
  - preferred_term: Osteoblast
    term:
      id: CL:0000062
      label: osteoblast
  biological_processes:
  - preferred_term: FGFR signaling pathway
    term:
      id: GO:0008543
      label: fibroblast growth factor receptor signaling pathway
    modifier: INCREASED
  evidence:
  - reference: PMID:29019756
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Skeletal disorders caused by type 1 mutations include Pfeiffer syndrome (PS) and osteoglophonic dysplasia"
    explanation: Confirms osteoglophonic dysplasia is caused by FGFR1 (type 1) mutations.
  downstream:
  - target: Premature Cranial Suture Fusion
  - target: Impaired Endochondral Ossification
  - target: Aberrant Fibrous Tissue Formation
- name: Premature Cranial Suture Fusion
  description: >-
    Constitutive FGFR1 activation drives premature osteoblast differentiation at
    cranial suture margins, causing premature suture fusion (craniosynostosis) and
    resulting in abnormal skull shape with frontal bossing and midface hypoplasia.
  biological_processes:
  - preferred_term: Cranial suture morphogenesis
    term:
      id: GO:0060363
      label: cranial suture morphogenesis
  evidence:
  - reference: PMID:38648328
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Osteoglophonic dysplasia (OGD) is characterized by multisuture craniosynostosis (including cloverleaf skull)"
    explanation: GeneReviews directly identifies multisuture craniosynostosis as a defining manifestation of OGD.
- name: Impaired Endochondral Ossification
  description: >-
    FGFR1 overactivation impairs normal endochondral ossification in the growth
    plates of long bones, leading to rhizomelic (proximal) limb shortening and
    short stature.
  biological_processes:
  - preferred_term: Endochondral ossification
    term:
      id: GO:0001958
      label: endochondral ossification
    modifier: DECREASED
  - preferred_term: Bone development
    term:
      id: GO:0060348
      label: bone development
    modifier: DECREASED
  evidence:
  - reference: PMID:29019756
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "FGFR1, FGFR2, and FGFR3 are crucial for both chondrogenesis and osteogenesis. Mutations in the genes encoding FGFRs, types 1-3, are responsible for various skeletal dysplasias and craniosynostosis syndromes."
    explanation: Establishes that FGFR1 mutations disrupt both chondrogenesis and osteogenesis, underlying the endochondral ossification defect.
- name: Aberrant Fibrous Tissue Formation
  description: >-
    OGD is characterized by nonossifying fibrous lesions within metaphyseal
    bone, producing the characteristic radiolucent defects that give the
    disorder its name ("hollowed-out bone").
  evidence:
  - reference: PMID:15625620
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder."
    explanation: White et al. explicitly identify nonossifying bone lesions as a characteristic feature of OGD.
phenotypes:
- category: Craniofacial
  name: Multisuture craniosynostosis
  description: >-
    Premature fusion of multiple cranial sutures is a defining manifestation and
    can be severe enough to produce a cloverleaf skull configuration.
  phenotype_term:
    preferred_term: Multisuture craniosynostosis
    term:
      id: HP:0001363
      label: Craniosynostosis
  evidence:
  - reference: PMID:38648328
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "CLINICAL CHARACTERISTICS: Osteoglophonic dysplasia (OGD) is characterized by multisuture craniosynostosis (including cloverleaf skull)"
    explanation: GeneReviews identifies multisuture craniosynostosis as a defining clinical feature of OGD.
- category: Musculoskeletal
  name: Disproportionate short-limb short stature
  description: >-
    Marked short stature with disproportionate limb shortening is a core skeletal
    manifestation.
  phenotype_term:
    preferred_term: Disproportionate short-limb short stature
    term:
      id: HP:0008873
      label: Disproportionate short-limb short stature
  evidence:
  - reference: PMID:29147600
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "She presented with disproportionate short stature, craniosynostosis, a prominent supraorbital ridge, delayed teeth eruption, hypodontia, and multiple nonossifying bone lesions in the femur, tibia, and fibula."
    explanation: The mutation-confirmed Indian case directly documents disproportionate short stature.
- category: Musculoskeletal
  name: Rhizomelia
  description: >-
    Proximal limb shortening contributes substantially to the dwarfing phenotype.
  phenotype_term:
    preferred_term: Rhizomelia
    term:
      id: HP:0008905
      label: Rhizomelia
  evidence:
  - reference: PMID:15625620
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder."
    explanation: White et al. describe rhizomelic dwarfism as a characteristic skeletal feature of OGD.
- category: Musculoskeletal
  name: Nonossifying fibromas of the long bones
  description: >-
    Multiple metaphyseal or cystic lucent lesions, often involving the long bones
    and sometimes the mandible, are a radiographic hallmark of OGD.
  phenotype_term:
    preferred_term: Nonossifying fibromas of the long bones
    term:
      id: HP:0000944
      label: Abnormal metaphysis morphology
  evidence:
  - reference: PMID:15625620
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder."
    explanation: White et al. identify nonossifying bone lesions as characteristic of OGD.
  - reference: PMID:29147600
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "She presented with disproportionate short stature, craniosynostosis, a prominent supraorbital ridge, delayed teeth eruption, hypodontia, and multiple nonossifying bone lesions in the femur, tibia, and fibula."
    explanation: The Indian case localizes the lesions to the long bones; HPO lacks a more specific nonossifying fibroma term, so abnormal metaphysis morphology is the closest grounded fit.
- category: Musculoskeletal
  name: Platyspondyly
  description: >-
    Flattened vertebral bodies are a recurrent radiographic feature.
  phenotype_term:
    preferred_term: Platyspondyly
    term:
      id: HP:0000926
      label: Platyspondyly
  evidence:
  - reference: PMID:8995175
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The appearance and gradual enlargement of fibrous cortical defects and multiple nonossifying fibromata are documented in this report of a 2-year-old boy with a very rare skeletal dysplasia known as osteoglophonic dysplasia, characterized by multiple and recurrent craniosynostoses, platyspondyly, short tubular bones, and epiphyseal dysplasia."
    explanation: Azouz and Kozlowski document platyspondyly as part of the characteristic radiographic phenotype.
- category: Musculoskeletal
  name: Epiphyseal dysplasia
  description: >-
    Epiphyseal involvement accompanies the spondylo-metaphyseal abnormalities in
    some affected individuals.
  phenotype_term:
    preferred_term: Epiphyseal dysplasia
    term:
      id: HP:0002656
      label: Epiphyseal dysplasia
  evidence:
  - reference: PMID:8995175
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The appearance and gradual enlargement of fibrous cortical defects and multiple nonossifying fibromata are documented in this report of a 2-year-old boy with a very rare skeletal dysplasia known as osteoglophonic dysplasia, characterized by multiple and recurrent craniosynostoses, platyspondyly, short tubular bones, and epiphyseal dysplasia."
    explanation: The same radiology report identifies epiphyseal dysplasia as part of the OGD skeletal pattern.
- category: Musculoskeletal
  name: Osteopenia
  description: >-
    Reduced bone density is part of the characteristic radiographic phenotype and
    likely contributes to bone fragility.
  phenotype_term:
    preferred_term: Osteopenia
    term:
      id: HP:0000938
      label: Osteopenia
  evidence:
  - reference: PMID:38648328
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Radiographs show copper beaten appearance to skull, multiple cystic long bone lesions consistent with non-ossifying fibromas, irregular vertebral bodies, and osteopenia with increased risk of fractures."
    explanation: GeneReviews includes osteopenia in the characteristic radiographic findings of OGD.
- category: Musculoskeletal
  name: Pathologic fracture
  description: >-
    Fragility fractures can occur through dysplastic cystic lesions and may lead
    to pseudoarthrosis in severe cases.
  phenotype_term:
    preferred_term: Pathologic fracture
    term:
      id: HP:0002756
      label: Pathologic fracture
  evidence:
  - reference: PMID:8958322
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Manifestations, not previously reported in osteoglophonic dysplasia, present in the propositus are spontaneous fractures resulting in pseudoarthroses through cystic and dysplastic foci in his proximal femoral shafts and right humerus"
    explanation: Spontaneous fractures through dysplastic bone are documented as an important, though apparently uncommon, complication.
- category: Craniofacial
  name: Frontal bossing
  description: >-
    Forehead prominence contributes to the characteristic craniofacial appearance.
  phenotype_term:
    preferred_term: Frontal bossing
    term:
      id: HP:0002007
      label: Frontal bossing
  evidence:
  - reference: PMID:35148738
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The details of the 4-year follow-up showed that the signs of OD were more pronounced, including dwarfism, frontal bossing, delayed skeletal maturation, anteverted nares, micrognathia, and prominent ears, but the patient's impacted teeth and edentulous jaws remained unchanged."
    explanation: The 4-year follow-up case directly documents frontal bossing.
- category: Craniofacial
  name: Prominent supraorbital ridges
  description: >-
    Supraorbital ridging is part of the characteristic facial gestalt.
  phenotype_term:
    preferred_term: Prominent supraorbital ridges
    term:
      id: HP:0000336
      label: Prominent supraorbital ridges
  evidence:
  - reference: PMID:15625620
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder."
    explanation: White et al. identify prominent supraorbital ridging as a characteristic craniofacial manifestation.
- category: Craniofacial
  name: Depressed nasal bridge
  description: >-
    A depressed nasal bridge is a recurring facial feature.
  phenotype_term:
    preferred_term: Depressed nasal bridge
    term:
      id: HP:0005280
      label: Depressed nasal bridge
  evidence:
  - reference: PMID:15625620
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder."
    explanation: White et al. describe depressed nasal bridge as part of the characteristic OGD facial phenotype.
- category: Craniofacial
  name: Proptosis
  description: >-
    Ocular prominence is part of the distinctive craniofacial phenotype.
  phenotype_term:
    preferred_term: Proptosis
    term:
      id: HP:0000520
      label: Proptosis
  evidence:
  - reference: PMID:38648328
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
    explanation: GeneReviews includes proptosis among the distinctive craniofacial features of OGD.
- category: Craniofacial
  name: Hypertelorism
  description: >-
    Widely spaced eyes are part of the characteristic craniofacial dysmorphism.
  phenotype_term:
    preferred_term: Hypertelorism
    term:
      id: HP:0000316
      label: Hypertelorism
  evidence:
  - reference: PMID:38648328
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
    explanation: The GeneReviews summary uses "widely spaced eyes," best represented by the HPO term hypertelorism.
- category: Craniofacial
  name: Midface retrusion
  description: >-
    Midfacial hypoplasia or retrusion is a recurrent and clinically important
    facial manifestation.
  phenotype_term:
    preferred_term: Midface retrusion
    term:
      id: HP:0011800
      label: Midface retrusion
  evidence:
  - reference: PMID:38648328
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
    explanation: GeneReviews includes midface retrusion in the characteristic craniofacial pattern.
- category: Craniofacial
  name: Short nose
  description: >-
    Short nasal length is part of the recurring OGD facial gestalt.
  phenotype_term:
    preferred_term: Short nose
    term:
      id: HP:0003196
      label: Short nose
  evidence:
  - reference: PMID:38648328
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
    explanation: Short nose is included in the GeneReviews craniofacial feature summary.
- category: Craniofacial
  name: Anteverted nares
  description: >-
    Upturned nostrils are part of the typical craniofacial phenotype.
  phenotype_term:
    preferred_term: Anteverted nares
    term:
      id: HP:0000463
      label: Anteverted nares
  evidence:
  - reference: PMID:35148738
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The details of the 4-year follow-up showed that the signs of OD were more pronounced, including dwarfism, frontal bossing, delayed skeletal maturation, anteverted nares, micrognathia, and prominent ears, but the patient's impacted teeth and edentulous jaws remained unchanged."
    explanation: The 4-year follow-up case directly documents anteverted nares.
- category: Craniofacial
  name: Low-set ears
  description: >-
    Low-set ears are part of the broader craniofacial dysmorphism.
  phenotype_term:
    preferred_term: Low-set ears
    term:
      id: HP:0000369
      label: Low-set ears
  evidence:
  - reference: PMID:38648328
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
    explanation: GeneReviews includes low-set ears in the characteristic craniofacial phenotype.
- category: Craniofacial
  name: High palate
  description: >-
    A high palate contributes to the characteristic craniofacial and dental
    phenotype.
  phenotype_term:
    preferred_term: High palate
    term:
      id: HP:0000218
      label: High palate
  evidence:
  - reference: PMID:38648328
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
    explanation: GeneReviews includes high palate in the craniofacial phenotype summary.
- category: Dental
  name: Delayed eruption of teeth
  description: >-
    Tooth eruption is often severely delayed and may progress to functional
    failure of eruption.
  phenotype_term:
    preferred_term: Delayed eruption of teeth
    term:
      id: HP:0000684
      label: Delayed eruption of teeth
  evidence:
  - reference: PMID:29147600
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "She presented with disproportionate short stature, craniosynostosis, a prominent supraorbital ridge, delayed teeth eruption, hypodontia, and multiple nonossifying bone lesions in the femur, tibia, and fibula."
    explanation: The Indian mutation-confirmed case directly documents delayed eruption of teeth.
- category: Dental
  name: Impacted teeth
  description: >-
    Multiple permanent teeth may remain unerupted and impacted despite root
    development.
  phenotype_term:
    preferred_term: Impacted tooth
    term:
      id: HP:0011079
      label: Impacted tooth
  evidence:
  - reference: PMID:16918680
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Radiographically, multiple lucent lesions were present in the tubular bones and mandible as well as several impacted teeth."
    explanation: Roberts et al. directly document multiple impacted teeth in a long-term follow-up case.
- category: Dental
  name: Hypodontia
  description: >-
    Reduced tooth number is a recurrent dental manifestation; some reports also
    describe clinically absent dentition.
  phenotype_term:
    preferred_term: Hypodontia
    term:
      id: HP:0000668
      label: Hypodontia
  evidence:
  - reference: PMID:29147600
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Rhizomelic dwarfism, craniosynostosis, impacted teeth, hypodontia or anodontia, and multiple nonossifying bone lesions are the salient features of this condition."
    explanation: Kuthiroly et al. list hypodontia, sometimes progressing to clinical anodontia, among the salient features of OGD.
- category: Dental
  name: Gingival overgrowth
  description: >-
    Gingival tissue overgrowth contributes to the characteristic oral phenotype.
  phenotype_term:
    preferred_term: Gingival overgrowth
    term:
      id: HP:0000212
      label: Gingival overgrowth
  evidence:
  - reference: PMID:38648328
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
    explanation: GeneReviews includes gingival overgrowth among the characteristic craniofacial and oral features.
- category: Metabolic
  name: Hypophosphatemia
  description: >-
    Some patients develop hypophosphatemia, apparently related to excess FGF23.
  phenotype_term:
    preferred_term: Hypophosphatemia
    term:
      id: HP:0002148
      label: Hypophosphatemia
  evidence:
  - reference: PMID:40260920
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients may have hypophosphatemia due to high FGF23 levels."
    explanation: The 2025 OGD update explicitly identifies hypophosphatemia as part of the disease spectrum and links it to elevated FGF23.
- category: Musculoskeletal
  name: Overlapping toe
  description: >-
    Overlapping toes were recently reported as a newly recognized appendicular
    feature in two individuals with FGFR1-related OGD.
  phenotype_term:
    preferred_term: Overlapping toe
    term:
      id: HP:0001845
      label: Overlapping toe
  evidence:
  - reference: PMID:40260920
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Both showed classic symptoms as well as signs not previously reported, including elevated frontal temperature and overlapping toes."
    explanation: The 2025 case series expands the phenotype to include overlapping toes.
- category: Craniofacial
  name: Prognathism
  description: >-
    Relative mandibular prominence contributes to the characteristic craniofacial
    profile.
  phenotype_term:
    preferred_term: Mandibular prognathia
    term:
      id: HP:0000303
      label: Mandibular prognathia
  evidence:
  - reference: PMID:38648328
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "distinctive craniofacial features (prominent forehead, proptosis, widely spaced eyes, low-set ears, midface retrusion, short nose, anteverted nares, prognathism, high palate, failure of tooth eruption, and gingival overgrowth)"
    explanation: GeneReviews includes prognathism among the characteristic craniofacial features of OGD.
genetic:
- name: FGFR1 gain-of-function mutations
  association: Causative
  gene_term:
    preferred_term: FGFR1
    term:
      id: hgnc:3688
      label: FGFR1
  notes: >-
    Activating mutations in FGFR1 cause osteoglophonic dysplasia. The mutations
    lead to constitutive receptor activation affecting craniofacial and long bone
    development with characteristic nonossifying fibrous metaphyseal lesions.
  evidence:
  - reference: PMID:29019756
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Skeletal disorders caused by type 1 mutations include Pfeiffer syndrome (PS) and osteoglophonic dysplasia"
    explanation: Confirms FGFR1 mutations cause osteoglophonic dysplasia.
  - reference: CGGV:assertion_d958e743-2ca0-4bb9-a198-364dd58005c3-2021-03-22T203501.315Z
    reference_title: "FGFR1 / osteoglophonic dwarfism (Limited)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "FGFR1 | HGNC:3688 | osteoglophonic dwarfism | MONDO:0008150 | AD | Limited"
    explanation: ClinGen classifies the FGFR1-osteoglophonic dwarfism gene-disease relationship as limited with autosomal dominant inheritance.
treatments:
- name: Orthopedic management
  description: >-
    Orthopedic management of skeletal complications including rhizomelic dwarfism
    and fibrous bone lesions. Surgical intervention may be required for severe
    limb deformities.
  treatment_term:
    preferred_term: Orthopedic management
    term:
      id: MAXO:0000004
      label: surgical procedure
- name: Craniofacial surgery
  description: Surgical correction of craniosynostosis and midface hypoplasia as needed.
  treatment_term:
    preferred_term: Craniofacial surgery
    term:
      id: MAXO:0000004
      label: surgical procedure
references:
- reference: PMID:38648328
  title: "Osteoglophonic Dysplasia."
  tags:
  - GeneReviews
  findings: []
📚

References & Deep Research

References

1
PMID:38648328
Osteoglophonic Dysplasia.
No top-level findings curated for this source.

Deep Research

1
Osteoglophonic Dysplasia Deep Research Notes ▸

Osteoglophonic Dysplasia Deep Research Notes

Date: 2026-04-18 Curator: Codex manual synthesis

Scope

Disease: Osteoglophonic dysplasia

Focus for issue #1506: - phenotype section only - add clinically important manifestations backed by exact PMID text - include frequency or onset only when directly supported - remove unsupported obligate-style assertions

Core Phenotype Sources Used

  • PMID:15625620
  • Mutation-confirmed FGFR1 paper with direct abstract support for craniosynostosis, prominent supraorbital ridges, depressed nasal bridge, rhizomelic dwarfism, and nonossifying bone lesions.
  • PMID:16918680
  • Dental follow-up case with direct abstract support for multiple unerupted teeth, several impacted teeth, and lucent jaw/long-bone lesions.
  • PMID:29147600
  • Mutation-confirmed Indian case with direct abstract support for disproportionate short stature, delayed tooth eruption, hypodontia, long-bone nonossifying lesions, and hypophosphatemia.
  • PMID:35148738
  • Four-year follow-up dental case with direct abstract support for frontal bossing and anteverted nares.
  • PMID:38648328
  • 2024 GeneReviews synthesis with PMID-backed abstract text supporting multisuture craniosynostosis, multiple craniofacial features, delayed/failed tooth eruption, gingival overgrowth, osteopenia, and fracture risk.
  • PMID:8958322
  • Review/case report supporting delayed tooth eruption, rib expansion, speech/developmental issues, and rare spontaneous fractures with pseudoarthroses.
  • PMID:8995175
  • Radiology report supporting platyspondyly and epiphyseal dysplasia in addition to nonossifying fibromata.
  • PMID:40260920
  • 2025 phenotype update supporting hypophosphatemia as part of the spectrum and adding overlapping toes as a newly reported feature.

Included in YAML

Phenotypes added or materially strengthened: - multisuture craniosynostosis - disproportionate short-limb short stature - rhizomelia - nonossifying fibromas of the long bones - platyspondyly - epiphyseal dysplasia - osteopenia - pathologic fracture - frontal bossing - prominent supraorbital ridges - depressed nasal bridge - proptosis - hypertelorism - midface retrusion - short nose - anteverted nares - low-set ears - high palate - delayed eruption of teeth - impacted teeth - hypodontia - gingival overgrowth - hypophosphatemia - overlapping toe

Deliberate Omissions / Softening

  • No phenotype frequency: values were retained or added.
  • The available abstracts reliably support disease-phenotype association, but they do not provide direct quantitative frequency bands for these manifestations.
  • Bone age was not modeled.
  • PMID:29147600 reports advanced bone age, while PMID:35148738 reports delayed skeletal maturation, so the current literature is conflicting.
  • Developmental delay / speech delay were not promoted to core phenotypes.
  • PMID:8958322 describes them, but older reports such as PMID:7422392 and PMID:20339250 emphasize normal intelligence or later normal cognition, suggesting variable expression rather than a stable core manifestation.
  • Elevated frontal temperature from PMID:40260920 was not modeled.
  • It appears to be a newly reported observation in two individuals, but HPO grounding is less clear and clinical importance is currently less established than overlapping toes.
  • Short, broad hands and feet from PMID:38648328 were not separately encoded.
  • The review clearly notes distal extremity involvement, but the closest exact HPO fits were less clean than the other added manifestations, so I kept the YAML focused on stronger mappings first.