Brachydactyly type A1 (BDA1) is the first recorded Mendelian autosomal dominant disorder in humans, originally identified by Farabee in 1903. It is characterized by shortening or absence of the middle phalanges. Heterozygous missense mutations in the Indian Hedgehog (IHH) gene, which encodes a key signaling molecule in endochondral bone development, cause BDA1. The mutations affect multiple levels of Hedgehog signaling including protein stability, receptor binding, and interaction with extracellular components.
Ask a research question about Brachydactyly Type A1. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Brachydactyly Type A1
creation_date: '2026-02-13T00:31:42Z'
updated_date: '2026-05-08T18:54:20Z'
category: Mendelian
description: >
Brachydactyly type A1 (BDA1) is the first recorded Mendelian autosomal dominant
disorder in humans, originally identified by Farabee in 1903. It is characterized
by shortening or absence of the middle phalanges. Heterozygous missense mutations
in the Indian Hedgehog (IHH) gene, which encodes a key signaling molecule in
endochondral bone development, cause BDA1. The mutations affect multiple levels
of Hedgehog signaling including protein stability, receptor binding, and
interaction with extracellular components.
disease_term:
preferred_term: brachydactyly type A1
term:
id: MONDO:0007215
label: brachydactyly type A1
parents:
- Limb Development Disorders
inheritance:
- name: Autosomal Dominant
description: >
Autosomal dominant inheritance, historically the first recorded
Mendelian autosomal dominant trait in humans (Farabee 1903).
evidence:
- reference: PMID:11455389
reference_title: "Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1."
supports: SUPPORT
snippet: "first recorded example of a human anomaly with Mendelian autosomal-dominant inheritance"
explanation: "BDA1 is historically significant as the first documented autosomal dominant human trait."
prevalence:
- population: Reported pedigrees worldwide
percentage: Unknown
notes: >-
Population prevalence has not been established. Brachydactyly type A1 is
documented mainly through multigenerational pedigrees and small molecularly
characterized family series rather than formal epidemiologic studies.
evidence:
- reference: PMID:19464397
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "We investigated six affected members of a large Swedish family segregating autosomal dominant brachymesophalangia."
explanation: >-
This molecular report illustrates that published BDA1 data are largely
family based rather than population based.
pathophysiology:
- name: Impaired IHH-Patched1 Receptor Signaling
description: >
Indian Hedgehog (IHH) is a secreted signaling molecule that binds the
receptor Patched1 (PTC1) to regulate chondrocyte proliferation and
differentiation in the growth plate via the Smoothened signaling pathway.
BDA1-causing missense mutations cluster in the N-terminal signaling
domain and reduce IHH binding to PTC1, diminishing its capacity to
induce cellular differentiation during endochondral ossification.
biological_processes:
- preferred_term: Smoothened Signaling Pathway
term:
id: GO:0007224
label: smoothened signaling pathway
- preferred_term: Endochondral Ossification
term:
id: GO:0001958
label: endochondral ossification
cell_types:
- preferred_term: Chondrocyte
term:
id: CL:0000138
label: chondrocyte
evidence:
- reference: PMID:11455389
reference_title: "Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1."
supports: SUPPORT
snippet: "mutations in IHH, which encodes Indian hedgehog, cause BDA-1"
explanation: "Identifies IHH as the causative gene for BDA1."
- reference: PMID:11455389
reference_title: "Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1."
supports: SUPPORT
snippet: "three heterozygous missense mutations in the region encoding the amino-terminal signaling domain"
explanation: "Mutations cluster in the IHH N-terminal signaling domain."
- reference: PMID:21537345
reference_title: "Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels."
supports: SUPPORT
snippet: "all three mutations affected Hh binding to the receptor Patched1 (PTC1), reducing its capacity to induce cellular differentiation"
explanation: "Demonstrates that BDA1 mutations impair IHH-Patched1 receptor binding and reduce signaling capacity."
- name: IHH Protein Instability and Trafficking Defects
description: >
BDA1 mutations also affect IHH protein stability, intracellular
trafficking, and interaction with extracellular matrix components.
The E95K and D100E mutations cause temperature-sensitive and
calcium-dependent instability of the IHH N-terminal domain, leading
to increased lysosomal degradation and reduced secretion. These
multi-level effects on Hedgehog signaling compound the receptor
binding defect.
biological_processes:
- preferred_term: Chondrocyte Differentiation
term:
id: GO:0002062
label: chondrocyte differentiation
evidence:
- reference: PMID:21537345
reference_title: "Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels."
supports: SUPPORT
snippet: "E95K and D100E mutations led to a temperature-sensitive and calcium-dependent instability of IhhN"
explanation: "Shows that specific BDA1 mutations cause protein instability under physiological conditions."
- reference: PMID:21537345
reference_title: "Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels."
supports: SUPPORT
snippet: "these IHH mutations affect Hh signaling at multiple levels, causing abnormal bone development and abnormal digit formation"
explanation: "Establishes the multi-level disruption of Hedgehog signaling as the pathogenic mechanism."
phenotypes:
- name: Type A1 Brachydactyly
description: >
The defining digital pattern of BDA1, caused by shortening or absence
of the middle phalanges with variable expressivity across affected
families.
phenotype_term:
preferred_term: Type A1 brachydactyly
term:
id: HP:0009371
label: Type A1 brachydactyly
evidence:
- reference: PMID:11455389
reference_title: "Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1."
supports: SUPPORT
snippet: "Brachydactyly type A-1 (BDA-1; MIM 112500) is characterized by shortening or missing of the middle phalanges"
explanation: "Defines the cardinal phenotype of BDA1."
- reference: PMID:21537345
reference_title: "Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels."
supports: SUPPORT
snippet: "Brachydactyly type A1 (BDA1), the first recorded Mendelian autosomal dominant disorder in humans, is characterized by a shortening or absence of the middle phalanges"
explanation: "Confirms middle phalanx shortening/absence as the defining feature."
- reference: PMID:32209048
reference_title: "A novel variant of IHH in a Chinese family with brachydactyly type 1."
supports: SUPPORT
snippet: "The variant co-segregated with BDA-1 in the pedigree, showed 100% penetrance for phalange phenotype with variable expressivity."
explanation: "A five-generation family showed fully penetrant but variably severe phalangeal involvement."
- name: Short Middle Phalanx of Finger
description: >
Uniform shortening of the finger middle phalanges is the core skeletal
abnormality in classic BDA1.
phenotype_term:
preferred_term: Short middle phalanx of finger
term:
id: HP:0005819
label: Short middle phalanx of finger
evidence:
- reference: PMID:34315464
reference_title: "Deletion of 2 amino acids in IHH in a Japanese family with brachydactyly type A1."
supports: SUPPORT
snippet: "Brachydactyly type A1 (BDA1) is an autosomal dominant disorder characterized by uniform shortening of the middle phalanges in all digits."
explanation: "Directly supports uniform shortening of the finger middle phalanges in a molecularly confirmed BDA1 family."
- reference: PMID:18629882
reference_title: "Deletion of 1 amino acid in Indian hedgehog leads to brachydactylyA1."
supports: SUPPORT
snippet: "Brachydactyly type A1 is a limb malformation characterized by a uniform shortening of the middle phalanges in all digits."
explanation: "Independent family report confirms uniform middle-phalanx shortening as the key digital abnormality."
- name: Short Middle Phalanx of Toe
description: >
Toe middle phalanges can also be shortened or absent in BDA1, showing
that the malformation affects both hands and feet.
phenotype_term:
preferred_term: Short middle phalanx of toe
term:
id: HP:0003795
label: Short middle phalanx of toe
evidence:
- reference: PMID:30651074
reference_title: "p.E95K mutation in Indian hedgehog causing brachydactyly type A1 impairs IHH/Gli1 downstream transcriptional regulation."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "Brachydactyly type A1 (BDA1, OMIM 112500) is a rare inherited malformation characterized primarily by shortness or absence of middle bones of fingers and toes."
explanation: "Supports toe middle-phalanx involvement as part of the core BDA1 malformation pattern."
- reference: PMID:40606564
reference_title: "A Novel Heterozygous IHH c.331_333del Mutation Identified in a Fetus with Brachydactyly Type A1 Causes IHH Protein Maturation Failure in HEK293T Cells."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Brachydactyly A1 (BDA1) is a rare disorder characterized by the disproportionate shortening of fingers and/or toes with or without symphalangism."
explanation: "Recent prenatal case report independently supports toe shortening within the BDA1 phenotype spectrum."
- name: Short Stature
description: >
Short stature has been reported in some molecularly confirmed BDA1
families and appears variable rather than obligatory.
phenotype_term:
preferred_term: Short stature
term:
id: HP:0004322
label: Short stature
evidence:
- reference: PMID:34315464
reference_title: "Deletion of 2 amino acids in IHH in a Japanese family with brachydactyly type A1."
supports: SUPPORT
snippet: "The proband, a 9-year-old boy, his siblings, and his father had shortened digits and a short stature of variable severity."
explanation: "Supports short stature as a variable associated manifestation in a molecularly confirmed BDA1 family."
genetic:
- name: IHH Missense Mutations
association: Causative
notes: >
Heterozygous missense mutations in the N-terminal signaling domain
of IHH. Known mutations include E95K, D100E, and E131K. The three
mutant amino acids are conserved across all vertebrates and
invertebrates and are predicted to be adjacent on the IHH protein
surface. E95K changes a negatively charged area to positively
charged in a calcium-binding groove; D100E alters local tertiary
structure.
evidence:
- reference: PMID:11455389
reference_title: "Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1."
supports: SUPPORT
snippet: "three heterozygous missense mutations in the region encoding the amino-terminal signaling domain in all affected members of three large, unrelated families"
explanation: "Three independent families with distinct IHH missense mutations establish genotype-phenotype relationship."
- reference: PMID:11455389
reference_title: "Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1."
supports: SUPPORT
snippet: "The three mutant amino acids, which are conserved across all vertebrates and invertebrates studied so far, are predicted to be adjacent on the surface of IHH"
explanation: "Deep evolutionary conservation and surface clustering suggest a critical functional domain."
- reference: PMID:21537345
reference_title: "Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels."
supports: SUPPORT
snippet: "Heterozygous missense mutations in the Indian Hedgehog (IHH) gene have been identified as a cause of BDA1"
explanation: "Confirms IHH missense mutations as the established cause of BDA1."
diagnosis:
- name: Clinical-radiographic and IHH molecular diagnosis
description: >-
Diagnosis is supported by the characteristic clinical and radiographic
pattern of shortened or absent middle phalanges and confirmed by
identifying heterozygous IHH variants in affected families.
diagnosis_term:
preferred_term: genetic testing
term:
id: MAXO:0000127
label: genetic testing
results: IHH variant detection plus middle-phalanx shortening or absence.
evidence:
- reference: PMID:11455389
reference_title: "Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Brachydactyly type A-1 (BDA-1; MIM 112500) is characterized by shortening or missing of the middle phalanges"
explanation: The defining skeletal pattern provides the clinical-radiographic basis for diagnosis.
- reference: PMID:11455389
reference_title: "Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-1."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Here we show that mutations in IHH, which encodes Indian hedgehog, cause BDA-1."
explanation: This supports IHH molecular testing as confirmatory for BDA1.
treatments:
- name: Genetic Counseling
description: >
Genetic counseling for affected families given autosomal dominant
inheritance and the historical significance of BDA1 as the first
recorded Mendelian trait.
treatment_term:
preferred_term: genetic counseling
term:
id: MAXO:0000079
label: genetic counseling
references:
- reference: DOI:10.1002/ajmg.a.33761
title: Brachydactyly type A1 with short humerus and associated skeletal features
found_in:
- Brachydactyly_Type_A1-deep-research-falcon.md
findings:
- statement: We report on a three‐generation family affected with an osteochondrodysplasia transmitted as an autosomal dominant trait.
supporting_text: We report on a three‐generation family affected with an osteochondrodysplasia transmitted as an autosomal dominant trait.
evidence:
- reference: DOI:10.1002/ajmg.a.33761
reference_title: Brachydactyly type A1 with short humerus and associated skeletal features
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: We report on a three‐generation family affected with an osteochondrodysplasia transmitted as an autosomal dominant trait.
explanation: Deep research cited this publication as relevant literature for Brachydactyly Type A1.
- reference: DOI:10.1177/1753193413514363
title: Embryology of familial (non-syndromic) brachydactyly of the hand
found_in:
- Brachydactyly_Type_A1-deep-research-falcon.md
findings:
- statement: Embryology of familial (non-syndromic) brachydactyly of the hand
supporting_text: Isolated familial non-syndromic brachydactyly is interesting from the embryological point of view because the phenotypes of isolated brachydactyly are frequently overlapping, yet they are caused by different gene mutations and the ring finger is frequently relatively preserved.
evidence:
- reference: DOI:10.1177/1753193413514363
reference_title: Embryology of familial (non-syndromic) brachydactyly of the hand
supports: SUPPORT
evidence_source: OTHER
snippet: Isolated familial non-syndromic brachydactyly is interesting from the embryological point of view because the phenotypes of isolated brachydactyly are frequently overlapping, yet they are caused by different gene mutations and the ring finger is frequently relatively preserved.
explanation: Deep research cited this publication as relevant literature for Brachydactyly Type A1.
- reference: DOI:10.20381/ruor-2868
title: 'The Genetic Heterogeneity of Brachydactyly Type A1: Identifying the Molecular Pathways'
found_in:
- Brachydactyly_Type_A1-deep-research-falcon.md
findings:
- statement: Brachydactyly type A1 (BDA1) is a rare autosomal dominant trait characterized by the shortening of the middle phalanges of digits 2-5 and of the proximal phalange of digit 1 in both hands and feet.
supporting_text: Brachydactyly type A1 (BDA1) is a rare autosomal dominant trait characterized by the shortening of the middle phalanges of digits 2-5 and of the proximal phalange of digit 1 in both hands and feet.
evidence:
- reference: DOI:10.20381/ruor-2868
reference_title: 'The Genetic Heterogeneity of Brachydactyly Type A1: Identifying the Molecular Pathways'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Brachydactyly type A1 (BDA1) is a rare autosomal dominant trait characterized by the shortening of the middle phalanges of digits 2-5 and of the proximal phalange of digit 1 in both hands and feet.
explanation: Deep research cited this publication as relevant literature for Brachydactyly Type A1.
- reference: DOI:10.3389/fgene.2022.814786
title: 'Case Report: Brachydactyly Type A1 Induced by a Novel Variant of in-Frame Insertion in the IHH Gene'
found_in:
- Brachydactyly_Type_A1-deep-research-falcon.md
findings:
- statement: Brachydactyly type A1 (BDA1) is an autosomal dominant inherited disease characterized by the shortness/absence of the middle phalanges, which can be induced by mutations in the Indian hedgehog gene (IHH).
supporting_text: Brachydactyly type A1 (BDA1) is an autosomal dominant inherited disease characterized by the shortness/absence of the middle phalanges, which can be induced by mutations in the Indian hedgehog gene (IHH).
evidence:
- reference: DOI:10.3389/fgene.2022.814786
reference_title: 'Case Report: Brachydactyly Type A1 Induced by a Novel Variant of in-Frame Insertion in the IHH Gene'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Brachydactyly type A1 (BDA1) is an autosomal dominant inherited disease characterized by the shortness/absence of the middle phalanges, which can be induced by mutations in the Indian hedgehog gene (IHH).
explanation: Deep research cited this publication as relevant literature for Brachydactyly Type A1.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on Brachydactyly Type A1 covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.
For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.
Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed
Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Search first: CTD, PubMed, PheGenI, GxE databases
Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC
For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities
For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype
Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser
Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Search first: CDC databases, WHO, PubMed, NHANES
Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON
Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Search first: PubMed, Gene Ontology, Reactome
Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types
Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Search first: OMIM, Orphanet, HPO, PubMed
Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.
Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Search first: NSGC resources, ACMG guidelines, GeneReviews
Search first: Clinical guidelines, FDA approvals, PubMed
Search first: NCBI Taxonomy
Search first: VBO (Vertebrate Breed Ontology)
Search first: NCBI Gene
Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease
This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details
Brachydactyly type A1 (BDA1) is a rare, typically autosomal-dominant, congenital digital malformation primarily characterized by hypoplasia/aplasia of the middle phalanges of digits 2–5, often with short proximal phalanges of the thumb and big toe and occasional symphalangism. (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3) The best-established causal gene is IHH (Indian hedgehog), with pathogenic variants clustering in the N-terminal signaling fragment (classically codons ~95–154) and recurrent hotspots at residues such as E95, D100, and E131. (racacho2015thegeneticheterogeneity pages 72-76, zeng2022casereportbrachydactyly pages 1-2) Recent case-level work (2024) underscores that some IHH-related families present with mild/non-classical BDA1 plus short stature and may be misclassified as idiopathic short stature; whole-exome sequencing (WES) can resolve diagnosis, and recombinant human growth hormone (rhGH) therapy improved height SDS in a small family case report. (chen2024shortstaturewith pages 1-2, chen2024shortstaturewith pages 2-4)
BDA1 is an isolated brachydactyly subtype in which shortening is mainly confined to the middle phalanges: “middle phalanges of all digits are variably short or rudimentary and are occasionally fused with terminal phalanges,” and “the proximal phalanges of the thumbs and big toes are short.” (temtamy2008brachydactyly pages 2-5) Radiographically, classification relies on the selective pattern of middle phalanx hypoplasia/aplasia on standard postero-anterior (PA) hand radiographs. (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3)
The knowledge base content below integrates: * Aggregated disease-level resources/reviews (e.g., Orphanet Journal of Rare Diseases review). (temtamy2008brachydactyly pages 2-5) * Radiology review evidence for diagnostic imaging hallmarks. (david2015isolatedandsyndromic pages 1-3) * Family case reports/series and molecular diagnostics/functional follow-up reports. (zeng2022casereportbrachydactyly pages 1-2, chen2024shortstaturewith pages 2-4, zhu2025anovelheterozygous pages 1-2)
BDA1 is a Mendelian congenital limb malformation primarily caused by germline pathogenic variants affecting endochondral ossification signaling pathways—most prominently IHH. (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3)
Genetic risk factors (causal variants): * IHH heterozygous variants are the canonical cause; classic reviews identify IHH mutations at 2q35–36. (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3) * Additional reported causal genes/loci include GDF5 and BMPR1B in genetic synthesis work; these converge on BMP/TGF-β axis biology relevant to digit formation and can phenocopy/overlap BDA1. (racacho2015thegeneticheterogeneity pages 111-116, racacho2015thegeneticheterogeneity pages 98-102)
Environmental risk factors: No environmental, infectious, or lifestyle risk factors are established in the retrieved evidence, consistent with a primary Mendelian etiology.
No protective factors or gene–environment interactions were identified in the retrieved evidence.
Digital skeletal phenotypes * Middle phalanges of digits 2–5 are variably short/absent; can be fused to distal/terminal phalanges (symphalangism). (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3) * Thumb proximal phalanx and big toe proximal phalanx often short. (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3) * Metacarpals can be short with broad epiphyses; distal phalanges may be short; digit 2 and 5 often most affected. (david2015isolatedandsyndromic pages 1-3)
Suggested HPO terms (non-exhaustive) * Brachydactyly — HP:0001156 * Brachydactyly, type A1 — (HPO term exists in many installations; not verified in retrieved evidence) * Symphalangism — HP:0001204 * Clinodactyly — HP:0004209 * Short stature (variable) — HP:0004322 (lacombe2010brachydactylytypea1 pages 3-5, chen2024shortstaturewith pages 2-4)
No validated QoL instrument data (e.g., SF-36/EQ-5D) were found in the retrieved evidence. Functional limitation is typically the driver of intervention decisions. (temtamy2008brachydactyly pages 2-5)
Primary causal gene: * IHH (Indian hedgehog). (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3)
Additional reported genes/loci (evidence in retrieved context but less canonical): * GDF5, BMPR1B, and a locus at 5p13.3–p13.2 (BDA1B). (temtamy2008brachydactyly pages 2-5, racacho2015thegeneticheterogeneity pages 111-116, racacho2015thegeneticheterogeneity pages 98-102)
A recurring theme is that BDA1-causing IHH variants cluster in the N-terminal signaling fragment. Genetic synthesis evidence states: “all of the BDA1-causing IHH mutations are missense and are limited to a 59 amino acid region… (codons 95–154).” (racacho2015thegeneticheterogeneity pages 72-76) Hotspots/recurrent residues include codons/residues E95, D100, and E131, among others; case reports add in-frame indels and frameshift examples. (racacho2015thegeneticheterogeneity pages 72-76, zeng2022casereportbrachydactyly pages 1-2, chen2024shortstaturewith pages 2-4) Examples in the retrieved evidence: * In-frame duplication: IHH NM_002181.4 c.383_415dup, p.(R128_H138dup). (zeng2022casereportbrachydactyly pages 1-2) * Frameshift (short stature + non-classical BDA1): IHH c.387_388insC, p.Thr130Hisfs18. (chen2024shortstaturewith pages 1-2) * In-frame deletion (prenatal case; functional maturation defect):* IHH c.331_333delCTG, p.Leu111del. (zhu2025anovelheterozygous pages 1-2)
Allele frequency: population allele-frequency values (gnomAD/1000G) were not available in retrieved tool evidence (gap).
A recent functional report highlights the importance of precursor processing and maturation: IHH is synthesized as a precursor and autocatalytically generates an active N-terminal signaling fragment; the p.Leu111del variant led to increased precursor with reduced mature functional IHH in HEK293T assays, consistent with “protein maturation failure.” (zhu2025anovelheterozygous pages 1-2)
No specific environmental/lifestyle/toxin/infectious contributors were identified in the retrieved evidence; the condition is primarily genetic.
IHH is central to growth plate biology and endochondral ossification. The 2024 case report explicitly summarizes that IHH “regulates proliferation and differentiation of chondrocytes and is essential for bone formation,” and “coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways,” referencing the Ihh–PTHrP feedback loop. (chen2024shortstaturewith pages 8-8) Mechanistic chain (high-level): 1. Upstream trigger: germline pathogenic variant in IHH (or related pathway genes). (temtamy2008brachydactyly pages 2-5, zeng2022casereportbrachydactyly pages 1-2) 2. Molecular dysfunction: reduced functional IHH (maturation/secretion/binding defects) or altered hedgehog signaling output. (zhu2025anovelheterozygous pages 1-2) 3. Cellular/tissue consequence: disrupted chondrocyte proliferation/differentiation gradients and growth plate signaling, altering cartilage template growth for phalanges/metacarpals. (chen2024shortstaturewith pages 8-8) 4. Clinical phenotype: congenital shortening/aplasia of middle phalanges ± symphalangism and variable short stature. (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3)
Primary structures: * Middle phalanges (digits 2–5), thumb proximal phalanx, toe phalanges, and sometimes metacarpals/metatarsals. (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3) Growth plate cartilage is the key tissue context. (chen2024shortstaturewith pages 8-8)
Suggested UBERON terms: * Phalanx — UBERON:0006002 * Metacarpal bone — UBERON:0011137 * Metatarsal bone — UBERON:0011138 * Growth plate cartilage — UBERON:0004367
Typical onset: congenital. (temtamy2008brachydactyly pages 2-5) Critical periods: embryonic and postnatal growth plate development (implied by IHH growth plate function). (chen2024shortstaturewith pages 8-8) Progression: not a progressive systemic disorder; skeletal proportions are established developmentally and remain stable, though secondary issues (e.g., arthritis) have been reported in some families. (racacho2015thegeneticheterogeneity pages 72-76)
Classic descriptions indicate autosomal dominant inheritance (“denoting autosomal dominant inheritance”). (temtamy2008brachydactyly pages 2-5)
Marked phenotypic heterogeneity and variable expressivity across families is documented; one synthesis notes “remarkable phenotypic heterogeneity.” (racacho2015thegeneticheterogeneity pages 72-76)
A key knowledge-base limitation is the lack of formal epidemiology: “No epidemiological studies have been reported. It is a rare hand malformation with only few pedigrees reported.” (temtamy2008brachydactyly pages 2-5)
Diagnosis relies on clinical exam + anthropometry + radiographs; “X-ray of hands on postero-anterior (PA) view show the selective distribution of the hypoplasia and aplasia of the middle phalanges.” (temtamy2008brachydactyly pages 2-5) A radiology review emphasizes that standard PA radiographs are first-line to classify subtype and localize shortening, and that BDA1 shows short/absent middle phalanges with occasional fusion and often short metacarpals with broad epiphyses. (david2015isolatedandsyndromic pages 1-3)
Modern implementation is WES in families with mild skeletal signs and short stature: * In a 2024 family with short stature and non-classical BDA1, WES identified a heterozygous IHH frameshift (c.387_388insC; p.Thr130Hisfs*18) with Sanger confirmation. (chen2024shortstaturewith pages 2-4) Similarly, case reports identify novel in-frame IHH insertions in multi-generation pedigrees. (zeng2022casereportbrachydactyly pages 1-2)
Differentials reported in a 2022 case report include Robinow syndrome, Feingold syndrome, and Temtamy preaxial brachydactyly syndrome, reflecting the need to distinguish isolated BDA1 from syndromic brachydactylies. (zeng2022casereportbrachydactyly pages 1-2)
BDA1 is generally compatible with normal life expectancy; morbidity is primarily functional/cosmetic. Surgical intervention is typically reserved for function/cosmesis. (temtamy2008brachydactyly pages 2-5) No quantitative mortality/survival statistics were found in the retrieved evidence (gap).
A commonly cited management approach is conservative: * “Plastic surgery is only indicated if the brachydactyly affects hand function or for cosmetic reasons… Physical therapy and ergotherapy may ameliorate hand function.” (temtamy2008brachydactyly pages 2-5) A 2022 case report similarly notes most patients are treated only if function is affected or for cosmetic reasons. (zeng2022casereportbrachydactyly pages 1-2)
Suggested MAXO terms: * Surgical procedure — MAXO:0000004 * Physical therapy — MAXO:0000011 * Occupational therapy — MAXO:0000014
rhGH in selected IHH-related short stature presentations: A 2024 report treated two siblings with rhGH (33 μg/kg/day) for 4 years, observing height SDS changes of +2.54 (boy) and +1.86 (girl), with “No noticeable adverse effect.” (chen2024shortstaturewith pages 1-2) Interpretation: this is not a corrective therapy for brachydactyly per se, but a real-world implementation relevant when BDA1 co-occurs with clinically significant short stature and growth hormone axis abnormalities. (chen2024shortstaturewith pages 2-4)
No BDA1-specific interventional clinical trials were retrieved; however, mechanistic literature referenced in a 2024 report notes Smoothened agonist (SAG) rescue in Ihh-deficiency models, suggesting pathway-modulation concepts in broader skeletal dysplasia research. (chen2024shortstaturewith pages 8-8)
No primary prevention is applicable for this Mendelian condition. Prevention focuses on genetic counseling, cascade testing, and reproductive options when a familial variant is known. (temtamy2008brachydactyly pages 2-5) Prenatal phenotyping with ultrasound plus WES has been used in recent fetal IHH-related BDA1 diagnosis. (zhu2025anovelheterozygous pages 1-2)
Suggested MAXO terms: Genetic counseling — MAXO:0000055.
No naturally occurring veterinary analogs were identified in the retrieved evidence.
Evidence supporting pathway relevance includes: * Bmpr1b-null mice exhibit phalange-restricted brachydactyly, supporting the role of BMP receptor biology in digit development. (racacho2015thegeneticheterogeneity pages 111-116) * Growth-plate models of Ihh deficiency and pharmacologic manipulation (e.g., SAG) are referenced in recent clinical mechanistic summaries. (chen2024shortstaturewith pages 8-8) Limitations: these models are not necessarily allele-matched to the common human BDA1 IHH hotspot variants.
A schematic classification figure including a BDA1 panel is available in the Temtamy & Aglan review. (temtamy2008brachydactyly media a1b197b0)
| Domain | Key knowledge-base fields | Suggested ontology terms | Supporting citation IDs |
|---|---|---|---|
| Disease identifiers / names | Disease: Brachydactyly type A1 (BDA1); isolated brachydactyly / brachymesophalangy predominantly affecting middle phalanges; OMIM: 112500; historic alternate locus BDA1B at 5p13.3-p13.2; information here is derived from aggregated disease-level literature/reviews plus family case reports and case series. | Suggested MONDO: Brachydactyly type A1 (MONDO not confirmed in retrieved evidence); MeSH/ICD/Orphanet identifiers not directly confirmed in retrieved context. | (temtamy2008brachydactyly pages 2-5, zeng2022casereportbrachydactyly pages 1-2, racacho2015thegeneticheterogeneity pages 84-88) |
| Inheritance / population genetics | Usually autosomal dominant with generally high/complete penetrance reported in classic descriptions; marked variable expressivity between and within families; rare evidence for semi-dominant behavior in some GDF5-related BDA1 presentations (milder heterozygotes, more severe homozygotes). Founder and recurrent hotspot mutations have been described for some IHH alleles. | HP: Autosomal dominant inheritance HP:0000006; Variable expressivity HP:0003828. | (temtamy2008brachydactyly pages 2-5, racacho2015thegeneticheterogeneity pages 84-88, racacho2015thegeneticheterogeneity pages 72-76, racacho2015thegeneticheterogeneity pages 98-102) |
| Core phenotypes | Congenital shortening/aplasia of middle phalanges of digits 2-5, often most severe in digits 2 and 5; short proximal phalanx of thumb and sometimes hallux; occasional fusion of middle and terminal phalanges (symphalangism); short/broad metacarpals; short toes; clinodactyly; absent distal finger creases; variable short stature and mild limb shortening in some families. | HP: Brachydactyly HP:0001156; Aplasia/Hypoplasia of middle phalanges of the hand HP:0009843/HP:0009882; Short thumb HP:0009778; Toe brachydactyly HP:0001773; Symphalangism HP:0001204; Clinodactyly HP:0004209; Short stature HP:0004322. | (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3, lacombe2010brachydactylytypea1 pages 3-5, zeng2022casereportbrachydactyly pages 1-2, chen2024shortstaturewith pages 2-4) |
| Radiographic hallmarks | Postero-anterior hand radiographs show selective hypoplasia/aplasia of middle phalanges; short or absent middle phalanges, occasional fusion with distal phalanges, short distal phalanges, short metacarpals with broad epiphyses; “chess pawn-shaped” distal bone described in classic BDA1; hand X-rays are central to subtype classification. | HP: Abnormality of hand bone morphology HP:0011304; Short middle phalanx of the 2nd finger HP:0009871; Short middle phalanx of the 5th finger HP:0009175. | (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3, racacho2015thegeneticheterogeneity pages 72-76, zhu2025anovelheterozygous pages 10-11, temtamy2008brachydactyly media a1b197b0) |
| Causal genes / loci | Primary causal gene: IHH (Indian hedgehog signaling molecule); additional reported BDA1 genes/loci include GDF5, BMPR1B, and a mapped locus at 5p13.3-p13.2. IHH explains a substantial fraction of molecularly solved cases (~40% cited in review-level evidence). | HGNC: IHH, GDF5, BMPR1B. | (racacho2015thegeneticheterogeneity pages 84-88, racacho2015thegeneticheterogeneity pages 111-116, racacho2015thegeneticheterogeneity pages 98-102, temtamy2008brachydactyly pages 2-5) |
| Pathogenic variants / hotspots | IHH BDA1 variants cluster in the N-terminal active/signaling fragment, especially codons 95-154; recurrent/hotspot residues include E95 (e.g., p.Glu95del / p.Glu95Lys), D100 (p.Asp100Asn/Glu), L111del, R128_H138dup, Thr130Hisfs*18, E131K. Variant classes include mostly missense, plus in-frame insertion/deletion and rare frameshift changes. GDF5 BDA1 variants include cysteine-disrupting missense alleles affecting the mature domain; BMPR1B missense/splice variants also reported. Germline origin is implied/observed. | Sequence Ontology suggestions: missense_variant, inframe_insertion, inframe_deletion, frameshift_variant, splice_acceptor_variant. | (racacho2015thegeneticheterogeneity pages 72-76, zeng2022casereportbrachydactyly pages 1-2, chen2024shortstaturewith pages 2-4, zhu2025anovelheterozygous pages 1-2, zhu2025anovelheterozygous pages 10-11, racacho2015thegeneticheterogeneity pages 111-116, racacho2015thegeneticheterogeneity pages 98-102) |
| Mechanism / pathways | Disease reflects disturbed endochondral ossification and growth-plate signaling. IHH normally regulates chondrocyte proliferation/differentiation and couples chondrogenesis to osteogenesis through IHH–PTCH1–SMO–GLI signaling and the IHH–PTHrP feedback loop. BDA1-associated variants can reduce mature functional IHH, impair IHH-PTC/PTCH binding, alter secretion/maturation, and downstream perturb digit cartilage template growth. BDA1 genes converge on BMP-SMAD / GDF5-BMPR1B signaling interacting with IHH-PTHrP biology. | GO: endochondral ossification GO:0001958; chondrocyte differentiation GO:0002062; regulation of chondrocyte differentiation GO:0032330; hedgehog signaling pathway GO:0007224; ossification GO:0001503. Key nodes: IHH, PTCH1, SMO, GLI1/2/3, PTHLH/PTHrP, PTH1R, GDF5, BMPR1B, SMADs. | (chen2024shortstaturewith pages 8-8, zhu2025anovelheterozygous pages 1-2, racacho2015thegeneticheterogeneity pages 84-88, racacho2015thegeneticheterogeneity pages 111-116, racacho2015thegeneticheterogeneity pages 98-102, alqattan2014embryologyoffamilial pages 3-7) |
| Anatomy / cell types | Primarily affects phalanges, metacarpals, metatarsals, and growth-plate cartilage of hands/feet; in some families also short humerus/femur or ulna-related changes. Key cell type is the growth plate chondrocyte. | UBERON: phalanx UBERON:0006002; metacarpal bone UBERON:0011137; metatarsal bone UBERON:0011138; growth plate cartilage UBERON:0004367. CL: chondrocyte CL:0000138; hypertrophic chondrocyte CL:0000218. | (lacombe2010brachydactylytypea1 pages 3-5, david2015isolatedandsyndromic pages 1-3, chen2024shortstaturewith pages 8-8) |
| Onset / course / prognosis | Typically congenital and usually non-progressive/stable as a structural limb malformation; lifelong but generally compatible with normal lifespan. Functional impact is often mild, though dexterity/cosmetic concerns and short stature may prompt evaluation. Osteoarthritis/arthritis has occasionally been reported in some families. | HP: Congenital onset HP:0003577; Abnormal hand morphology HP:0005922. | (temtamy2008brachydactyly pages 2-5, racacho2015thegeneticheterogeneity pages 72-76, zeng2022casereportbrachydactyly pages 1-2) |
| Epidemiology | No robust prevalence/incidence estimates for BDA1 were identified in the retrieved evidence. Reviews state brachydactylies are rare overall and specifically note that BDA1 is a rare hand malformation with only a few pedigrees/case series reported; prevalence figures around ~2% apply to types A3 and D, not A1. | Rare disease designation appropriate; no disease-specific frequency ontology assignment supported by retrieved evidence. | (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3, zeng2022casereportbrachydactyly pages 1-2) |
| Diagnostics | Diagnosis is primarily clinical + radiographic (PA hand/foot X-rays), followed by molecular confirmation. Current real-world testing uses WES with Sanger confirmation; targeted skeletal dysplasia / short stature / brachydactyly panels are reasonable when phenotype is suggestive. Differential diagnosis includes other isolated brachydactylies and syndromic entities such as Robinow syndrome, Feingold syndrome, and Temtamy preaxial brachydactyly syndrome; radiographs help subtype classification. | MAXO not applicable here; HPO terms above support phenotyping. Testing methods: WES, Sanger sequencing, multigene panel. | (temtamy2008brachydactyly pages 2-5, david2015isolatedandsyndromic pages 1-3, zeng2022casereportbrachydactyly pages 1-2, chen2024shortstaturewith pages 2-4, chen2024shortstaturewith pages 1-2) |
| Management / treatment | No disease-modifying therapy established for classic isolated BDA1. Management is usually conservative, with plastic/orthopedic surgery only if hand function or cosmesis is significantly affected; physical therapy/ergotherapy (occupational therapy) may improve function. In recent IHH-related short stature families, recombinant human growth hormone (rhGH) produced substantial height SDS gains over 4 years without major adverse effects, but evidence is limited to case-level reports and applies mainly to selected short-stature presentations rather than hand malformation correction. | MAXO: physical therapy MAXO:0000011; occupational therapy MAXO:0000014; surgical procedure MAXO:0000004; growth hormone therapy MAXO:0010020. | (temtamy2008brachydactyly pages 2-5, zeng2022casereportbrachydactyly pages 1-2, chen2024shortstaturewith pages 2-4, chen2024shortstaturewith pages 1-2, chen2024shortstaturewith pages 8-8) |
| Prevention / counseling | No primary environmental prevention known for this Mendelian malformation. Key preventive actions are genetic counseling, family segregation testing, and consideration of prenatal/preimplantation testing when a familial pathogenic variant is known. | MAXO: genetic counseling MAXO:0000055; cascade genetic testing MAXO:0000127. | (temtamy2008brachydactyly pages 2-5, chen2024shortstaturewith pages 2-4, chen2024shortstaturewith pages 1-2) |
| Model organism / comparative evidence | Mouse and developmental studies support pathway relevance: Bmpr1b-null mice show phalange-restricted brachydactyly; broader skeletal biology literature shows Ihh is essential for growth-plate homeostasis and chondrocyte hypertrophy/differentiation. Model evidence is mechanistically strong but does not perfectly recapitulate the full human BDA1 hand phenotype for every allele. | GO as above; model organism: Mus musculus. | (racacho2015thegeneticheterogeneity pages 111-116, chen2024shortstaturewith pages 8-8) |
Table: This table condenses the main disease-knowledge fields for brachydactyly type A1, including phenotype, genetics, mechanism, diagnosis, and management. It is designed for rapid knowledge-base population and each row links to supporting evidence context IDs.
Within the retrieved tool evidence, the following could not be confirmed and should be filled by targeted database queries (OMIM/Orphanet/MONDO/MeSH/GTR/ClinVar/gnomAD) in a subsequent pass: MONDO ID; Orphanet ORPHA code; ICD-10/ICD-11 codes; MeSH descriptor; ClinVar variant classifications and population allele frequencies; and validated QoL statistics.
References
(temtamy2008brachydactyly pages 2-5): Samia A Temtamy and Mona S Aglan. Brachydactyly. Orphanet Journal of Rare Diseases, Jun 2008. URL: https://doi.org/10.1186/1750-1172-3-15, doi:10.1186/1750-1172-3-15. This article has 223 citations and is from a peer-reviewed journal.
(david2015isolatedandsyndromic pages 1-3): A. David, M. Vincent, M.-P. Quéré, T. Lefrançois, E. Frampas, and A. David. Isolated and syndromic brachydactylies: diagnostic value of hand x-rays. Diagnostic and interventional imaging, 96 5:443-8, May 2015. URL: https://doi.org/10.1016/j.diii.2014.12.007, doi:10.1016/j.diii.2014.12.007. This article has 27 citations and is from a peer-reviewed journal.
(racacho2015thegeneticheterogeneity pages 72-76): Lemuel Jean Racacho. The genetic heterogeneity of brachydactyly type a1: identifying the molecular pathways. ArXiv, Mar 2015. URL: https://doi.org/10.20381/ruor-2868, doi:10.20381/ruor-2868. This article has 0 citations.
(zeng2022casereportbrachydactyly pages 1-2): Feier Zeng, Huan Liu, Xuyang Xia, Yang Shu, Wei Cheng, Heng Xu, Geng Yin, and Qibing Xie. Case report: brachydactyly type a1 induced by a novel variant of in-frame insertion in the ihh gene. Frontiers in Genetics, May 2022. URL: https://doi.org/10.3389/fgene.2022.814786, doi:10.3389/fgene.2022.814786. This article has 3 citations and is from a peer-reviewed journal.
(chen2024shortstaturewith pages 1-2): Yulin Chen, Mingyue Yin, Yiyi Lu, Zhiya Dong, Wenli Lu, Lin Lin, and Yuan Xiao. Short stature with brachydactyly caused by a novel mutation in the ihh gene and response to 4-year growth hormone therapy: a case report. Translational Pediatrics, 13:856-863, May 2024. URL: https://doi.org/10.21037/tp-23-578, doi:10.21037/tp-23-578. This article has 3 citations and is from a peer-reviewed journal.
(chen2024shortstaturewith pages 2-4): Yulin Chen, Mingyue Yin, Yiyi Lu, Zhiya Dong, Wenli Lu, Lin Lin, and Yuan Xiao. Short stature with brachydactyly caused by a novel mutation in the ihh gene and response to 4-year growth hormone therapy: a case report. Translational Pediatrics, 13:856-863, May 2024. URL: https://doi.org/10.21037/tp-23-578, doi:10.21037/tp-23-578. This article has 3 citations and is from a peer-reviewed journal.
(zhu2025anovelheterozygous pages 1-2): Ting Zhu, Lijie Guan, Dan Chen, Yi Luo, Mianmian Zhu, Rongyue Sun, Jiamin Shi, Qiu Wang, Yuan Chen, Yihong Wang, Hongwei Wang, Zhongqiu Lu, and Dan Wang. A novel heterozygous ihh c.331_333del mutation identified in a fetus with brachydactyly type a1 causes ihh protein maturation failure in hek293t cells. Phenomics, 5:123-136, Dec 2025. URL: https://doi.org/10.1007/s43657-024-00191-9, doi:10.1007/s43657-024-00191-9. This article has 1 citations.
(racacho2015thegeneticheterogeneity pages 111-116): Lemuel Jean Racacho. The genetic heterogeneity of brachydactyly type a1: identifying the molecular pathways. ArXiv, Mar 2015. URL: https://doi.org/10.20381/ruor-2868, doi:10.20381/ruor-2868. This article has 0 citations.
(racacho2015thegeneticheterogeneity pages 98-102): Lemuel Jean Racacho. The genetic heterogeneity of brachydactyly type a1: identifying the molecular pathways. ArXiv, Mar 2015. URL: https://doi.org/10.20381/ruor-2868, doi:10.20381/ruor-2868. This article has 0 citations.
(lacombe2010brachydactylytypea1 pages 3-5): Didier Lacombe, Marie‐Ange Delrue, Caroline Rooryck, Fanny Morice‐Picard, Benoît Arveiler, Brigitte Maugey‐Laulom, Stefan Mundlos, Annick Toutain, and Jean‐François Chateil. Brachydactyly type a1 with short humerus and associated skeletal features. American Journal of Medical Genetics Part A, 152A:3016-3021, Dec 2010. URL: https://doi.org/10.1002/ajmg.a.33761, doi:10.1002/ajmg.a.33761. This article has 4 citations.
(chen2024shortstaturewith pages 8-8): Yulin Chen, Mingyue Yin, Yiyi Lu, Zhiya Dong, Wenli Lu, Lin Lin, and Yuan Xiao. Short stature with brachydactyly caused by a novel mutation in the ihh gene and response to 4-year growth hormone therapy: a case report. Translational Pediatrics, 13:856-863, May 2024. URL: https://doi.org/10.21037/tp-23-578, doi:10.21037/tp-23-578. This article has 3 citations and is from a peer-reviewed journal.
(temtamy2008brachydactyly media a1b197b0): Samia A Temtamy and Mona S Aglan. Brachydactyly. Orphanet Journal of Rare Diseases, Jun 2008. URL: https://doi.org/10.1186/1750-1172-3-15, doi:10.1186/1750-1172-3-15. This article has 223 citations and is from a peer-reviewed journal.
(racacho2015thegeneticheterogeneity pages 84-88): Lemuel Jean Racacho. The genetic heterogeneity of brachydactyly type a1: identifying the molecular pathways. ArXiv, Mar 2015. URL: https://doi.org/10.20381/ruor-2868, doi:10.20381/ruor-2868. This article has 0 citations.
(zhu2025anovelheterozygous pages 10-11): Ting Zhu, Lijie Guan, Dan Chen, Yi Luo, Mianmian Zhu, Rongyue Sun, Jiamin Shi, Qiu Wang, Yuan Chen, Yihong Wang, Hongwei Wang, Zhongqiu Lu, and Dan Wang. A novel heterozygous ihh c.331_333del mutation identified in a fetus with brachydactyly type a1 causes ihh protein maturation failure in hek293t cells. Phenomics, 5:123-136, Dec 2025. URL: https://doi.org/10.1007/s43657-024-00191-9, doi:10.1007/s43657-024-00191-9. This article has 1 citations.
(alqattan2014embryologyoffamilial pages 3-7): M. M. Al-Qattan. Embryology of familial (non-syndromic) brachydactyly of the hand. Journal of Hand Surgery (European Volume), 39:926-933, Nov 2014. URL: https://doi.org/10.1177/1753193413514363, doi:10.1177/1753193413514363. This article has 12 citations.