Brachydactyly Type D

Mendelian MONDO:0007222 Pathograph 9 Show in embeddings browser Limb Development Disorders

Brachydactyly type D ("stub thumb") is shortening and broadening of the distal phalanx of the thumb, unilateral or bilateral, with the rest of the hand essentially normal. It is by far the most common isolated brachydactyly together with type A3 — reported at 0.41% to 4.0% depending on population, and at 3.55% in a large genotyped Nepali cohort — which sets it apart from every other entity in the isolated brachydactyly group: those are known from a handful of pedigrees, this one is a recognisable normal-population variant that rarely reaches medical attention except for the short broad thumbnail. The short distal phalanx results from premature closure of its epiphysis rather than from failure to form a segment. Inheritance is autosomal dominant with reduced penetrance, and the molecular basis is largely unresolved: HOXD13 homeodomain missense substitutions produce limb phenotypes overlapping types D and E, which is the attribution the ISDS nosology records, but a genome-wide linkage scan of a combined BDD/BDE phenotype mapped instead to 7p15, so more than one locus is likely.

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1
Inheritance
3
Pathophys.
5
Phenotypes
9
Pathograph
2
Genes
2
Medical Actions
3
References
🏷

Classifications

ISDS Skeletal Nosology
brachydactyly without extraskeletal manifestations
👪

Inheritance

1
Autosomal Dominant with Reduced Penetrance HP:0000006
Autosomal dominant with reduced penetrance and frequent unilateral expression. Heritability of the combined BDD/BDE phenotype was estimated at 0.89 in a large extended Nepali pedigree, so the trait is strongly genetic even where a specific allele has not been found.
Autosomal dominant inheritance
Show evidence (2 references)
PMID:18554391 SUPPORT Other
"In isolated brachydactyly, the inheritance is mostly autosomal dominant with variable expressivity"
Establishes the dominant, variably expressed inheritance pattern of isolated brachydactyly.
PMID:24022874 SUPPORT Human Clinical
"The additive genetic heritability of BDD/BDE was highly significant"
A large extended pedigree establishes strong additive genetic determination of the trait.
⚙

Pathophysiology

3
Altered HOXD13 Homeodomain DNA Binding
HOXD13 is the most 5' gene of the HOXD cluster and encodes a homeodomain transcription factor that patterns the autopod. Most HOXD13 disease alleles are polyalanine expansions or frameshifts causing synpolydactyly; the two substitutions associated with type D and type E phenotypes instead sit inside the homeodomain itself. In vitro, Ile314Leu — at homeodomain position 47 — does not simply lose DNA binding but rebalances it, gaining affinity for a TTAC core target while losing affinity for TTAT. A mixed gain and loss of target selectivity, rather than a dosage change, is what distinguishes this allele class from the synpolydactyly alleles of the same gene.
HOXD13 hgnc:5136 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves HOXD13 (hgnc:5136). hgnc:5136 is a gene from the HUGO Gene Nomenclature Committee.
Regulation of Transcription by RNA Polymerase II GO:0006357 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves dysregulated Regulation of Transcription by RNA Polymerase II (GO:0006357). GO:0006357 is a biological process from the Gene Ontology. ↕ DYSREGULATED
DNA-binding Transcription Factor Activity GO:0003700 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves abnormal DNA-binding Transcription Factor Activity (GO:0003700). GO:0003700 is a molecular function from the Gene Ontology. ⚠ ABNORMAL
Downstream
Premature Closure of the Thumb Distal Phalangeal Epiphysis Deregulated autopod patterning changes the growth trajectory of the thumb terminal segment.
Show evidence (3 references)
PMID:12649808 SUPPORT Human Clinical
"Here, we describe two mutations of HOXD13 (923C-->G encoding Ser308Cys and 940A-->C encoding Ile314Leu) that cause missense substitutions within the homeodomain."
Identifies the homeodomain missense alleles associated with the type D/E phenotypes.
PMID:12649808 SUPPORT In Vitro
"the Ile314Leu mutation (which resides at the 47th position of the homeodomain) exhibited increased affinity for a target containing the core recognition sequence 5'-TTAC-3' but decreased affinity for a 5'-TTAT-3' target"
Shows the allele rebalances rather than abolishes target-site binding.
PMID:12649808 REFUTE In Vitro
"No consistent differences were found for the Ser308Cys mutation compared with the wild type"
A negative in vitro result that cuts against this node as stated: the Ser308Cys allele showed no detectable change in target-site binding, so altered DNA-binding transcription factor activity does not account for both homeodomain variants. The node holds for Ile314Leu; the mechanism by which Ser308Cys produces the same phenotype is unresolved.
Premature Closure of the Thumb Distal Phalangeal Epiphysis
Unlike the type A-C brachydactylies, in which a phalangeal segment fails to form or to segment properly, the type D thumb has all its segments — the distal phalanx simply stops growing early. Investigations attribute the short distal phalanx to early closure of its epiphysis; the base of the shortened phalanx is broader than the proximal phalangeal surface it articulates with, and the distal end is often hyperplastic. The mechanism is therefore one of growth-plate timing in a single skeletal element rather than of segment specification.
Chondrocyte CL:0000138 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves Chondrocyte (CL:0000138). CL:0000138 is a cell type from the Cell Ontology.
Endochondral Ossification GO:0001958 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal Endochondral Ossification (GO:0001958). GO:0001958 is a biological process from the Gene Ontology. ⚠ ABNORMAL Chondrocyte Proliferation GO:0035988 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased Chondrocyte Proliferation (GO:0035988). GO:0035988 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Short Broad Distal Phalanx of the Thumb Early epiphyseal fusion leaves a short, broad terminal thumb segment with a correspondingly short broad nail.
Show evidence (2 references)
PMID:18554391 SUPPORT Other
"Other investigations confirmed that the short distal pha- lanx of the thumb results from early closure of its epiphy- ses."
Identifies premature epiphyseal closure as the proximate mechanism. The quote preserves the hyphenated line breaks of the cached full text ("pha- lanx", "epiphy- ses"), which are a PDF artifact, not the source's own wording.
PMID:18554391 SUPPORT Other
"It has been noted that the base of the distal phalanx is broader than the surface of the proximal phalanx to which it articulates, and that the distal end of the bone often shows some hyperplasia."
Describes the characteristic broad, hyperplastic morphology of the shortened phalanx.
Short Broad Distal Phalanx of the Thumb
The realised phenotype: a short, broad distal phalanx of the thumb, unilateral or bilateral, giving the characteristic short wide thumbnail. Great toes may be affected in the same way, and the distal phalanges of other digits are sometimes broad and short — the serially homologous echo of the same lesion. Thumb function is typically unaffected, which is why the presentation is usually cosmetic.
Limb Morphogenesis GO:0035108 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal Limb Morphogenesis (GO:0035108). GO:0035108 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Downstream
Type D Brachydactyly
Short Distal Phalanx of the Thumb
Broad Distal Phalanx of the Thumb
Short Distal Phalanx of the Hallux
Broad Distal Phalanx of the Hallux
Show evidence (2 references)
PMID:18554391 SUPPORT Other
"Characteristically, the distal phalanx of the thumb alone is shortened."
Defines the isolated distal-thumb involvement that names the type.
PMID:18554391 SUPPORT Other
"The distal phalanges of other digits may also be broad and short. Great toes may be similarly affected."
Documents the serially homologous involvement of other digits and the great toes.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Brachydactyly Type D 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

5
Type D Brachydactyly OBLIGATE Skeletal HP:0005627 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Type D brachydactyly (HP:0005627). HP:0005627 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:18554391 SUPPORT Other
"Characteristically, the distal phalanx of the thumb alone is shortened."
Defines the cardinal phenotype of BDD.
Short Distal Phalanx of the Thumb OBLIGATE Skeletal HP:0009650 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Short distal phalanx of the thumb (HP:0009650). HP:0009650 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:18554391 SUPPORT Other
"Clinical evaluation and radiographs show a broad and short distal phalanx of thumbs, unilateral or bilateral."
Documents the broad short terminal thumb segment and its variable laterality.
Broad Distal Phalanx of the Thumb VERY_FREQUENT Skeletal HP:0009642 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Broad distal phalanx of the thumb (HP:0009642). HP:0009642 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:35722929 SUPPORT Human Clinical
"Brachydactyly Type D is a congenital condition of the thumb in which there is a short and broad thumbnail."
Describes the broad short nail that reflects the broad short phalanx.
Short Distal Phalanx of the Hallux OCCASIONAL Skeletal HP:0010076 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Aplasia/Hypoplasia of the distal phalanx of the hallux (HP:0010076). HP:0010076 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:18554391 SUPPORT Other
"Great toes may be similarly affected."
Documents hallux involvement in BDD.
Broad Distal Phalanx of the Hallux OCCASIONAL Skeletal HP:0010077 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Broad distal phalanx of the hallux (HP:0010077). HP:0010077 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:18554391 SUPPORT Other
"The distal phalanges of other digits may also be broad and short. Great toes may be similarly affected."
The review describes the involved digits, halluces included, as broad and short rather than merely short.
🧬

Genetic Associations

2
HOXD13 Homeodomain Missense Variants (Causative in a minority of cases)
Gene: HOXD13 hgnc:5136 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is HOXD13 (hgnc:5136). hgnc:5136 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: CAUSATIVE variant_origin: GERMLINE
Show evidence (2 references)
PMID:12649808 SUPPORT Human Clinical
"Both are associated with distinctive limb phenotypes in which brachydactyly of specific metacarpals, metatarsals, and phalangeal bones is the most constant feature, exhibiting overlap with brachydactyly types D and E."
The primary human genetic evidence linking HOXD13 to type D/E phenotypes.
PMID:18554391 REFUTE Other
"no gene or locus for BDD has yet been identified."
A 2008 review states no BDD gene had been identified, which is why the HOXD13 attribution should not be read as accounting for population BDD.
7p15 Susceptibility Locus (Linkage to a combined BDD/BDE phenotype)
relationship_type: SUSCEPTIBILITY variant_origin: GERMLINE
Show evidence (2 references)
PMID:24022874 SUPPORT Human Clinical
"Significant linkage of BDD/BDE was found to markers on chromosome 7p21-7p14 (peak LOD score = 3.74 at 7p15 between markers D7S493 and D7S516)."
Establishes a significant linkage signal outside the HOXD cluster.
PMID:24022874 SUPPORT Human Clinical
"Possible positional candidate genes in the one-lod support interval of this QTL include TWIST and the HOXA1-A13 cluster."
Names the candidate genes under the linkage peak; no causal variant was reported.
💊

Medical Actions

2
Observation and Reassurance
Action: supportive careNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is supportive care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. Ontology label: Supportive Care NCIT:C15747
BDD is common, does not impair thumb function in most people, and needs no treatment; the appropriate management for the majority is recognition and reassurance rather than intervention.
Show evidence (2 references)
PMID:35722929 SUPPORT Human Clinical
"Although the thumb function is often unaffected, some patients seek surgery for cosmetic improvement."
Confirms that function is usually preserved, so intervention is elective.
PMID:18554391 SUPPORT Other
"There is no specific management or treatment that is applicable to all forms of brachydactyly."
Supports a management approach directed by symptoms rather than by diagnosis.
Distraction Lengthening for Nail Deformity
Action: orthopedic surgical procedureNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is orthopedic surgical procedure (NCIT:C16186). NCIT:C16186 is a clinical intervention from the NCI Thesaurus. Ontology label: Orthopedic Surgical Procedure NCIT:C16186
Distraction lengthening of the short distal phalanx is an elective, cosmesis-directed procedure. In the largest reported series — 163 thumbs in 95 patients — mean thumbnail length rose from 9 mm to 15 mm and the nail length-to-width ratio normalised, without loss of thumb function or a visible scar.
Show evidence (2 references)
PMID:35722929 SUPPORT Human Clinical
"The mean thumbnail length improved from 9 mm to 15 mm, with a mean percentage increase of 62%."
Quantifies the anatomical result of distraction lengthening in 95 patients.
PMID:35722929 SUPPORT Human Clinical
"We conclude that aesthetic correction of short nail deformity in brachydactyly Type D can be achieved by distraction lengthening with high satisfaction and without functional impairment."
States the authors' overall outcome assessment for the procedure.
🔬

Diagnosis

1
Clinical-radiographic diagnosis
Clinical inspection and hand radiographs showing a short broad distal phalanx of one or both thumbs, with the rest of the hand normal. Molecular testing is not routine because the trait is common and usually unexplained; where it matters, HOXD13 is the candidate the nosology names. The main diagnostic task is separating isolated BDD from a syndromic short thumb.
physical examination NCIT:C20989 NCI Thesaurus (NCIT)
Results: Short broad distal phalanx of the thumb, unilateral or bilateral, on clinical evaluation and radiographs.
Show evidence (2 references)
PMID:18554391 SUPPORT Other
"Clinical evaluation and radiographs show a broad and short distal phalanx of thumbs, unilateral or bilateral."
States the diagnostic method and finding for BDD.
PMID:18554391 SUPPORT Other
"Diagnosis is clinical, anthropometric and radiological."
Establishes the clinical-radiographic basis of brachydactyly diagnosis.
📊

Prevalence

2
Worldwide, varying by population
Point Prevalence 410.0–4000.0 per 100,000 >1 in 1,000
Reported at 0.41% to 4.0% across populations, with particularly high rates among Israeli Arabs and in Japan. Expressed here as 410-4000 per 100,000. Type D and type A3 are the two isolated brachydactylies that are common rather than rare.
Show evidence (2 references)
PMID:18554391 SUPPORT Other
"This type of brachydactyly is common. The prevalence varies in different populations, ranging from 0.41% to 4.0%."
Gives the reported population prevalence range for BDD.
PMID:18554391 SUPPORT Other
"The various types of isolated brachydactyly are rare, except for types A3 and D."
Explicitly separates type D from the rare isolated brachydactylies.
Jirel ethnic group, eastern Nepal
Point Prevalence 3550.0 per 100,000 >1 in 1,000
3.55% of a 2,130-person radiographically phenotyped community sample, from a study designed to phenotype BDD and BDE systematically rather than ascertaining through clinics.
Show evidence (1 reference)
PMID:24022874 SUPPORT Human Clinical
"BDD was present in 3.55%, and BDE was present in 0.39%, of the study sample."
Gives a population-based BDD frequency from systematic radiographic phenotyping.
{ }

Source YAML

click to show 
name: Brachydactyly Type D
synonyms:
- BDD
- Stub thumb
- Clubbed thumb
creation_date: '2026-08-27T00:00:00Z'
category: Mendelian
description: >
  Brachydactyly type D ("stub thumb") is shortening and broadening of the distal
  phalanx of the thumb, unilateral or bilateral, with the rest of the hand
  essentially normal. It is by far the most common isolated brachydactyly
  together with type A3 — reported at 0.41% to 4.0% depending on population, and
  at 3.55% in a large genotyped Nepali cohort — which sets it apart from every
  other entity in the isolated brachydactyly group: those are known from a
  handful of pedigrees, this one is a recognisable normal-population variant that
  rarely reaches medical attention except for the short broad thumbnail. The
  short distal phalanx results from premature closure of its epiphysis rather
  than from failure to form a segment. Inheritance is autosomal dominant with
  reduced penetrance, and the molecular basis is largely unresolved: HOXD13
  homeodomain missense substitutions produce limb phenotypes overlapping types D
  and E, which is the attribution the ISDS nosology records, but a genome-wide
  linkage scan of a combined BDD/BDE phenotype mapped instead to 7p15, so more
  than one locus is likely.
disease_term:
  preferred_term: brachydactyly type D
  term:
    id: MONDO:0007222
    label: brachydactyly type D
parents:
- Limb Development Disorders
inheritance:
- name: Autosomal Dominant with Reduced Penetrance
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  description: >-
    Autosomal dominant with reduced penetrance and frequent unilateral
    expression. Heritability of the combined BDD/BDE phenotype was estimated at
    0.89 in a large extended Nepali pedigree, so the trait is strongly genetic
    even where a specific allele has not been found.
  evidence:
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "In isolated brachydactyly, the inheritance is mostly autosomal dominant with variable expressivity"
    explanation: Establishes the dominant, variably expressed inheritance pattern of isolated brachydactyly.
  - reference: PMID:24022874
    reference_title: Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the Jirel ethnic group in eastern Nepal.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The additive genetic heritability of BDD/BDE was highly significant"
    explanation: A large extended pedigree establishes strong additive genetic determination of the trait.
classifications:
  isds_skeletal_category:
  - classification_value: brachydactyly_without_extraskeletal_manifestations
    notes: >-
      ISDS Nosology of Genetic Skeletal Disorders, 2023 revision (Unger et al.,
      PMID:36779427), group 18 "Brachydactylies (isolated)", which lists
      brachydactyly type D (HOXD13; OMIM 113200). The HOXD13 attribution follows
      the nosology; note that most BDD is not molecularly solved and that the one
      genome-wide scan of a combined BDD/BDE phenotype implicated 7p15 rather
      than the HOXD cluster. The 2019 revision (PMID:31633310) placed type D in
      group 37 "Brachydactylies (without extraskeletal manifestations)". Per-row
      re-verification against the 2023 Table 1 is tracked in
      monarch-initiative/dismech#7867.
prevalence:
- population: Worldwide, varying by population
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_low: 410.0
  rate_high: 4000.0
  notes: >-
    Reported at 0.41% to 4.0% across populations, with particularly high rates
    among Israeli Arabs and in Japan. Expressed here as 410-4000 per 100,000.
    Type D and type A3 are the two isolated brachydactylies that are common
    rather than rare.
  evidence:
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "This type of brachydactyly is common. The prevalence varies in different populations, ranging from 0.41% to 4.0%."
    explanation: Gives the reported population prevalence range for BDD.
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The various types of isolated brachydactyly are rare, except for types A3 and D."
    explanation: Explicitly separates type D from the rare isolated brachydactylies.
- population: Jirel ethnic group, eastern Nepal
  measure_type: POINT_PREVALENCE
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 3550.0
  notes: >-
    3.55% of a 2,130-person radiographically phenotyped community sample, from a
    study designed to phenotype BDD and BDE systematically rather than
    ascertaining through clinics.
  evidence:
  - reference: PMID:24022874
    reference_title: Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the Jirel ethnic group in eastern Nepal.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "BDD was present in 3.55%, and BDE was present in 0.39%, of the study sample."
    explanation: Gives a population-based BDD frequency from systematic radiographic phenotyping.
pathophysiology:
- name: Altered HOXD13 Homeodomain DNA Binding
  conforms_to: "limb_digit_patterning_serial_homology#Limb Patterning Signal Perturbation"
  role: trigger
  biological_scale: MOLECULAR
  description: >
    HOXD13 is the most 5' gene of the HOXD cluster and encodes a homeodomain
    transcription factor that patterns the autopod. Most HOXD13 disease alleles
    are polyalanine expansions or frameshifts causing synpolydactyly; the two
    substitutions associated with type D and type E phenotypes instead sit inside
    the homeodomain itself. In vitro, Ile314Leu — at homeodomain position 47 —
    does not simply lose DNA binding but rebalances it, gaining affinity for a
    TTAC core target while losing affinity for TTAT. A mixed gain and loss of
    target selectivity, rather than a dosage change, is what distinguishes this
    allele class from the synpolydactyly alleles of the same gene.
  gene:
    preferred_term: HOXD13
    term:
      id: hgnc:5136
      label: HOXD13
  biological_processes:
  - preferred_term: Regulation of Transcription by RNA Polymerase II
    term:
      id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    modifier: DYSREGULATED
  molecular_functions:
  - preferred_term: DNA-binding Transcription Factor Activity
    term:
      id: GO:0003700
      label: DNA-binding transcription factor activity
    modifier: ABNORMAL
  evidence:
  - reference: PMID:12649808
    reference_title: Missense mutations in the homeodomain of HOXD13 are associated with brachydactyly types D and E.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Here, we describe two mutations of HOXD13 (923C-->G encoding Ser308Cys and 940A-->C encoding Ile314Leu) that cause missense substitutions within the homeodomain."
    explanation: Identifies the homeodomain missense alleles associated with the type D/E phenotypes.
  - reference: PMID:12649808
    reference_title: Missense mutations in the homeodomain of HOXD13 are associated with brachydactyly types D and E.
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "the Ile314Leu mutation (which resides at the 47th position of the homeodomain) exhibited increased affinity for a target containing the core recognition sequence 5'-TTAC-3' but decreased affinity for a 5'-TTAT-3' target"
    explanation: Shows the allele rebalances rather than abolishes target-site binding.
  - reference: PMID:12649808
    reference_title: Missense mutations in the homeodomain of HOXD13 are associated with brachydactyly types D and E.
    supports: REFUTE
    evidence_source: IN_VITRO
    snippet: "No consistent differences were found for the Ser308Cys mutation compared with the wild type"
    explanation: >-
      A negative in vitro result that cuts against this node as stated: the
      Ser308Cys allele showed no detectable change in target-site binding, so
      altered DNA-binding transcription factor activity does not account for
      both homeodomain variants. The node holds for Ile314Leu; the mechanism by
      which Ser308Cys produces the same phenotype is unresolved.
  downstream:
  - target: Premature Closure of the Thumb Distal Phalangeal Epiphysis
    description: >-
      Deregulated autopod patterning changes the growth trajectory of the thumb
      terminal segment.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:12649808
      reference_title: Missense mutations in the homeodomain of HOXD13 are associated with brachydactyly types D and E.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Both are associated with distinctive limb phenotypes in which brachydactyly of specific metacarpals, metatarsals, and phalangeal bones is the most constant feature, exhibiting overlap with brachydactyly types D and E."
      explanation: Connects the HOXD13 homeodomain alleles to the type D/E digital phenotypes.
- name: Premature Closure of the Thumb Distal Phalangeal Epiphysis
  conforms_to: "limb_digit_patterning_serial_homology#Disrupted Digit Number and Identity Specification"
  role: central_effector
  biological_scale: TISSUE
  description: >
    Unlike the type A-C brachydactylies, in which a phalangeal segment fails to
    form or to segment properly, the type D thumb has all its segments — the
    distal phalanx simply stops growing early. Investigations attribute the short
    distal phalanx to early closure of its epiphysis; the base of the shortened
    phalanx is broader than the proximal phalangeal surface it articulates with,
    and the distal end is often hyperplastic. The mechanism is therefore one of
    growth-plate timing in a single skeletal element rather than of segment
    specification.
  biological_processes:
  - preferred_term: Endochondral Ossification
    term:
      id: GO:0001958
      label: endochondral ossification
    modifier: ABNORMAL
  - preferred_term: Chondrocyte Proliferation
    term:
      id: GO:0035988
      label: chondrocyte proliferation
    modifier: DECREASED
  cell_types:
  - preferred_term: Chondrocyte
    term:
      id: CL:0000138
      label: chondrocyte
  evidence:
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Other investigations confirmed that the short distal pha- lanx of the thumb results from early closure of its epiphy- ses."
    explanation: >-
      Identifies premature epiphyseal closure as the proximate mechanism. The
      quote preserves the hyphenated line breaks of the cached full text
      ("pha- lanx", "epiphy- ses"), which are a PDF artifact, not the source's
      own wording.
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "It has been noted that the base of the distal phalanx is broader than the surface of the proximal phalanx to which it articulates, and that the distal end of the bone often shows some hyperplasia."
    explanation: Describes the characteristic broad, hyperplastic morphology of the shortened phalanx.
  downstream:
  - target: Short Broad Distal Phalanx of the Thumb
    description: >-
      Early epiphyseal fusion leaves a short, broad terminal thumb segment with a
      correspondingly short broad nail.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:35722929
      reference_title: Aesthetic correction of short nail deformity in congenital brachydactyly Type D by distraction lengthening.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Brachydactyly Type D is a congenital condition of the thumb in which there is a short and broad thumbnail."
      explanation: States the realised thumb and nail morphology.
- name: Short Broad Distal Phalanx of the Thumb
  conforms_to: "limb_digit_patterning_serial_homology#Serially Homologous Autopod Malformation"
  role: consequence
  biological_scale: TISSUE
  description: >
    The realised phenotype: a short, broad distal phalanx of the thumb,
    unilateral or bilateral, giving the characteristic short wide thumbnail.
    Great toes may be affected in the same way, and the distal phalanges of other
    digits are sometimes broad and short — the serially homologous echo of the
    same lesion. Thumb function is typically unaffected, which is why the
    presentation is usually cosmetic.
  biological_processes:
  - preferred_term: Limb Morphogenesis
    term:
      id: GO:0035108
      label: limb morphogenesis
    modifier: ABNORMAL
  evidence:
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Characteristically, the distal phalanx of the thumb alone is shortened."
    explanation: Defines the isolated distal-thumb involvement that names the type.
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The distal phalanges of other digits may also be broad and short. Great toes may be similarly affected."
    explanation: Documents the serially homologous involvement of other digits and the great toes.
  downstream:
  - target: Type D Brachydactyly
    causal_link_type: DIRECT
  - target: Short Distal Phalanx of the Thumb
    causal_link_type: DIRECT
  - target: Broad Distal Phalanx of the Thumb
    causal_link_type: DIRECT
  - target: Short Distal Phalanx of the Hallux
    causal_link_type: DIRECT
  - target: Broad Distal Phalanx of the Hallux
    causal_link_type: DIRECT
phenotypes:
- category: Skeletal
  name: Type D Brachydactyly
  description: >
    The defining pattern: a short, broad distal phalanx of the thumb with the
    rest of the hand essentially normal.
  phenotype_term:
    preferred_term: Type D brachydactyly
    term:
      id: HP:0005627
      label: Type D brachydactyly
  frequency: OBLIGATE
  evidence:
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Characteristically, the distal phalanx of the thumb alone is shortened."
    explanation: Defines the cardinal phenotype of BDD.
- category: Skeletal
  name: Short Distal Phalanx of the Thumb
  description: >
    Shortening of the thumb terminal phalanx, with a broad base and often a
    hyperplastic distal end; degrees vary and involvement may be unilateral.
  phenotype_term:
    preferred_term: Short distal phalanx of the thumb
    term:
      id: HP:0009650
      label: Short distal phalanx of the thumb
  frequency: OBLIGATE
  evidence:
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Clinical evaluation and radiographs show a broad and short distal phalanx of thumbs, unilateral or bilateral."
    explanation: Documents the broad short terminal thumb segment and its variable laterality.
- category: Skeletal
  name: Broad Distal Phalanx of the Thumb
  description: >
    The shortened phalanx is broad, giving the short wide nail that usually
    brings the trait to attention.
  phenotype_term:
    preferred_term: Broad distal phalanx of the thumb
    term:
      id: HP:0009642
      label: Broad distal phalanx of the thumb
  frequency: VERY_FREQUENT
  evidence:
  - reference: PMID:35722929
    reference_title: Aesthetic correction of short nail deformity in congenital brachydactyly Type D by distraction lengthening.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Brachydactyly Type D is a congenital condition of the thumb in which there is a short and broad thumbnail."
    explanation: Describes the broad short nail that reflects the broad short phalanx.
- category: Skeletal
  name: Short Distal Phalanx of the Hallux
  description: >
    The great toes may show the same shortening as the thumbs, the hindlimb
    counterpart of the same patterning lesion.
  phenotype_term:
    preferred_term: Aplasia/Hypoplasia of the distal phalanx of the hallux
    term:
      id: HP:0010076
      label: Aplasia/Hypoplasia of the distal phalanx of the hallux
  frequency: OCCASIONAL
  evidence:
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Great toes may be similarly affected."
    explanation: Documents hallux involvement in BDD.
- category: Skeletal
  name: Broad Distal Phalanx of the Hallux
  description: >
    The great toe mirrors the thumb: where it is involved, the terminal phalanx
    is broad as well as short.
  phenotype_term:
    preferred_term: Broad distal phalanx of the hallux
    term:
      id: HP:0010077
      label: Broad distal phalanx of the hallux
  frequency: OCCASIONAL
  evidence:
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The distal phalanges of other digits may also be broad and short. Great toes may be similarly affected."
    explanation: >-
      The review describes the involved digits, halluces included, as broad and
      short rather than merely short.
genetic:
- name: HOXD13 Homeodomain Missense Variants
  gene_term:
    preferred_term: HOXD13
    term:
      id: hgnc:5136
      label: HOXD13
  association: Causative in a minority of cases
  relationship_type: CAUSATIVE
  variant_origin: GERMLINE
  notes: >-
    Ser308Cys and Ile314Leu, both inside the homeodomain, were reported in two
    families with limb phenotypes overlapping types D and E, and this is the
    attribution the ISDS nosology carries for type D. Most BDD in the general
    population has no identified molecular cause; the review literature as
    recently as 2008 recorded no gene or locus for BDD.
  evidence:
  - reference: PMID:12649808
    reference_title: Missense mutations in the homeodomain of HOXD13 are associated with brachydactyly types D and E.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Both are associated with distinctive limb phenotypes in which brachydactyly of specific metacarpals, metatarsals, and phalangeal bones is the most constant feature, exhibiting overlap with brachydactyly types D and E."
    explanation: The primary human genetic evidence linking HOXD13 to type D/E phenotypes.
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: REFUTE
    evidence_source: OTHER
    snippet: "no gene or locus for BDD has yet been identified."
    explanation: >-
      A 2008 review states no BDD gene had been identified, which is why the
      HOXD13 attribution should not be read as accounting for population BDD.
- name: 7p15 Susceptibility Locus
  association: Linkage to a combined BDD/BDE phenotype
  relationship_type: SUSCEPTIBILITY
  variant_origin: GERMLINE
  notes: >-
    A variance-components genome scan of 1,722 genotyped members of a Nepali
    extended pedigree found significant linkage of the combined BDD/BDE trait to
    7p21-7p14, peaking at 7p15 — away from the HOXD cluster on 2q31. Candidate
    genes in the interval include TWIST and the HOXA cluster. The causal variant
    has not been identified, so this is a mapped locus rather than a gene.
  evidence:
  - reference: PMID:24022874
    reference_title: Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the Jirel ethnic group in eastern Nepal.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Significant linkage of BDD/BDE was found to markers on chromosome 7p21-7p14 (peak LOD score = 3.74 at 7p15 between markers D7S493 and D7S516)."
    explanation: Establishes a significant linkage signal outside the HOXD cluster.
  - reference: PMID:24022874
    reference_title: Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children and adults from the Jirel ethnic group in eastern Nepal.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Possible positional candidate genes in the one-lod support interval of this QTL include TWIST and the HOXA1-A13 cluster."
    explanation: Names the candidate genes under the linkage peak; no causal variant was reported.
diagnosis:
- name: Clinical-radiographic diagnosis
  description: >-
    Clinical inspection and hand radiographs showing a short broad distal phalanx
    of one or both thumbs, with the rest of the hand normal. Molecular testing is
    not routine because the trait is common and usually unexplained; where it
    matters, HOXD13 is the candidate the nosology names. The main diagnostic task
    is separating isolated BDD from a syndromic short thumb.
  diagnosis_term:
    preferred_term: physical examination
    term:
      id: NCIT:C20989
      label: Physical Examination
  results: >-
    Short broad distal phalanx of the thumb, unilateral or bilateral, on
    clinical evaluation and radiographs.
  evidence:
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Clinical evaluation and radiographs show a broad and short distal phalanx of thumbs, unilateral or bilateral."
    explanation: States the diagnostic method and finding for BDD.
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Diagnosis is clinical, anthropometric and radiological."
    explanation: Establishes the clinical-radiographic basis of brachydactyly diagnosis.
treatments:
- name: Observation and Reassurance
  description: >-
    BDD is common, does not impair thumb function in most people, and needs no
    treatment; the appropriate management for the majority is recognition and
    reassurance rather than intervention.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: supportive care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:35722929
    reference_title: Aesthetic correction of short nail deformity in congenital brachydactyly Type D by distraction lengthening.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Although the thumb function is often unaffected, some patients seek surgery for cosmetic improvement."
    explanation: Confirms that function is usually preserved, so intervention is elective.
  - reference: PMID:18554391
    reference_title: Brachydactyly.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "There is no specific management or treatment that is applicable to all forms of brachydactyly."
    explanation: Supports a management approach directed by symptoms rather than by diagnosis.
- name: Distraction Lengthening for Nail Deformity
  description: >-
    Distraction lengthening of the short distal phalanx is an elective,
    cosmesis-directed procedure. In the largest reported series — 163 thumbs in 95
    patients — mean thumbnail length rose from 9 mm to 15 mm and the nail
    length-to-width ratio normalised, without loss of thumb function or a visible
    scar.
  therapeutic_modality: SURGERY
  treatment_term:
    preferred_term: orthopedic surgical procedure
    term:
      id: NCIT:C16186
      label: Orthopedic Surgical Procedure
  evidence:
  - reference: PMID:35722929
    reference_title: Aesthetic correction of short nail deformity in congenital brachydactyly Type D by distraction lengthening.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The mean thumbnail length improved from 9 mm to 15 mm, with a mean percentage increase of 62%."
    explanation: Quantifies the anatomical result of distraction lengthening in 95 patients.
  - reference: PMID:35722929
    reference_title: Aesthetic correction of short nail deformity in congenital brachydactyly Type D by distraction lengthening.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We conclude that aesthetic correction of short nail deformity in brachydactyly Type D can be achieved by distraction lengthening with high satisfaction and without functional impairment."
    explanation: States the authors' overall outcome assessment for the procedure.
references:
- reference: PMID:19790289
  title: "The brachydactylies: a molecular disease family."
- reference: PMID:18554391
  title: Brachydactyly.
- reference: PMID:26698251
  title: "Concomitance of types D and E brachydactyly: a case report."
📚

References & Deep Research

References

3
PMID:19790289
The brachydactylies: a molecular disease family.
No top-level findings curated for this source.
PMID:18554391
Brachydactyly.
No top-level findings curated for this source.
PMID:26698251
Concomitance of types D and E brachydactyly: a case report.
No top-level findings curated for this source.