Microtia

Summary

Microtia (MONDO:0010920) is a disease with 1 cohort gene and 30 clinical trials. Top therapeutic interventions include bisphenol a.

At a glance

• Prevalence: 1-5 / 10 000 (Specific population) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 9
• Clinical trials: 30

Clinical features

Epidemiology

Prevalence records

17 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	38	Specific population	Validated
Point prevalence	1-9 / 100 000		France	Validated
Point prevalence	1-9 / 100 000		Sweden	Validated
Point prevalence	1-5 / 10 000		United States	Validated
Point prevalence	1-5 / 10 000		Finland	Validated
Prevalence at birth	1-9 / 100 000	3.7	France	Validated
Prevalence at birth	1-9 / 100 000	1.2	Italy	Validated
Prevalence at birth	1-9 / 100 000	2.1	Sweden	Validated
Prevalence at birth	1-5 / 10 000	22	United States	Validated
Prevalence at birth	1-5 / 10 000	43.4	Finland	Validated
Prevalence at birth	>1 / 1000	174	Ecuador	Validated
Prevalence at birth	6-9 / 10 000	83	Chile	Validated
Point prevalence	1-5 / 10 000		Worldwide	Not yet validated
Prevalence at birth	1-5 / 10 000	15.5	Worldwide	Not yet validated
Point prevalence	1-5 / 10 000		Europe	Not yet validated
Prevalence at birth	1-5 / 10 000	13	Europe	Not yet validated
Point prevalence	1-9 / 100 000		Italy	Not yet validated

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0008551	Microtia	Obligate (100%)
HP:0040119	Unilateral conductive hearing impairment	Very frequent (80-99%)
HP:0000377	Abnormal pinna morphology	Frequent (30-79%)
HP:0000413	Atresia of the external auditory canal	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0008589	Hypoplastic helices	Frequent (30-79%)
HP:0009892	Anotia	Frequent (30-79%)
HP:0001360	Holoprosencephaly	Occasional (5-29%)
HP:0007018	Attention deficit hyperactivity disorder	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	microtia
Mondo ID	MONDO:0010920
MeSH	C537772, D065817
OMIM	600674
Orphanet	83463
ICD-10-CM	Q17.2
ICD-11	2005415414
SNOMED CT	35045004
UMLS	C1833486
MedGen	322201
GARD	0000431
MedDRA	10027555
Is cancer (heuristic)	no

Also known as: anotia · congenital microtias · M-A · microtia, congenital · microtia-anotia · microtias, congenital

Data availability: 1 GenCC gene-disease record · 1 cell line.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › microtia

Related subtypes (51): disorder of sexual differentiation, hereditary neurocutaneous angioma, nevoid basal cell carcinoma syndrome, angioosteohypertrophic syndrome, Larsen syndrome, schwannomatosis, linear nevus sebaceous syndrome, lethal Larsen-like syndrome, pseudodiastrophic dysplasia, focal dermal hypoplasia, neurofibromatosis-Noonan syndrome, Becker nevus syndrome, Legius syndrome, bone fragility with contractures, arterial rupture, and deafness, blindness - scoliosis - arachnodactyly syndrome, cutis laxa - Marfanoid syndrome, Maffucci syndrome, hydrops fetalis, ankyloblepharon filiforme-imperforate anus syndrome, developmental anomaly of metabolic origin, progeroid syndrome, facial cleft, Desbuquois dysplasia, cysts and fistulae of the face and oral cavity, macroglossia, middle ear anomaly, cleft palate, cutis laxa, infectious embryofetopathy, toxic or drug-related embryofetopathy, hemihyperplasia-multiple lipomatosis syndrome, phakomatosis pigmentokeratotica, phakomatosis pigmentovascularis, PTEN hamartoma tumor syndrome, marfanoid habitus-inguinal hernia-advanced bone age syndrome, neurofibromatosis type 1, multiple congenital anomalies/dysmorphic syndrome, congenital limb malformation, hereditary hemorrhagic telangiectasia, urogenital tract malformation, congenital anomaly of kidney and urinary tract, anotia, central nervous system malformation, Ehlers-Danlos syndrome, X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome, joint laxity, short stature, and myopia, diaphragmatic malformation, abdominal wall malformation, port-wine nevi-mega cisterna magna-hydrocephalus syndrome, conjoined twins, TP63-related ectodermal dysplasia spectrum with limb and orofacial malformations

Subtypes (1): ear without helix

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
HOXA2	Strong	Autosomal dominant	bilateral microtia-deafness-cleft palate syndrome	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HOXA2	Orphanet:140963	Bilateral microtia-deafness-cleft palate syndrome
HOXA2	Orphanet:83463	Microtia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HOXA2	HGNC:5103	ENSG00000105996	O43364	Homeobox protein Hox-A2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HOXA2	Homeobox protein Hox-A2	Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HOXA2	Transcription factor	no		HD, Homeobox_Antennapedia_CS, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
descending thoracic aorta	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HOXA2	133	broad	yes	buccal mucosa cell, mucosa of transverse colon, descending thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HOXA2	1,256

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HOXA2	O43364	58.47

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	91.4×	0.014	HOXA2
Regulation of expression of SLITs and ROBOs	1	69.2×	0.014	HOXA2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
rhombomere 3 morphogenesis	1	16852.0×	0.001	HOXA2
rhombomere 2 development	1	8426.0×	0.001	HOXA2
brain segmentation	1	5617.3×	0.001	HOXA2
segment specification	1	2106.5×	0.002	HOXA2
embryonic viscerocranium morphogenesis	1	1685.2×	0.002	HOXA2
muscle structure development	1	1404.3×	0.002	HOXA2
osteoblast development	1	991.3×	0.002	HOXA2
cell fate determination	1	936.2×	0.002	HOXA2
pharyngeal system development	1	802.5×	0.002	HOXA2
motor neuron axon guidance	1	702.2×	0.002	HOXA2
middle ear morphogenesis	1	702.2×	0.002	HOXA2
dorsal/ventral pattern formation	1	421.3×	0.004	HOXA2
negative regulation of osteoblast differentiation	1	295.6×	0.005	HOXA2
negative regulation of neuron differentiation	1	271.8×	0.005	HOXA2
cellular response to retinoic acid	1	234.1×	0.005	HOXA2
anterior/posterior pattern specification	1	181.2×	0.006	HOXA2
positive regulation of transcription by RNA polymerase II	1	14.9×	0.071	HOXA2
regulation of transcription by RNA polymerase II	1	11.7×	0.086	HOXA2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HOXA2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	HOXA2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
HOXA2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 30.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	20
PHASE1/PHASE2	3
PHASE4	2
PHASE2	2
EARLY_PHASE1	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02518035	PHASE4	UNKNOWN	Silicone Gel to Improve Scar in Microtia Patients
NCT04192708	PHASE4	UNKNOWN	Study of Analgesic Efficacy of Nerve Blocks on Otoplastic Surgery
NCT05288790	PHASE2	RECRUITING	Microbiome Metabolites and Alcohol in HIV to Reduce CVD RCT
NCT06087874	PHASE2	RECRUITING	Preventive Effect of Perinatal Oral Probiotic Supplementation (POPS) on Neonatal Jaundice
NCT04399239	PHASE1/PHASE2	TERMINATED	AuriNovo for Auricular Reconstruction
NCT06072040	PHASE1/PHASE2	TERMINATED	Subcutaneous Implant Combination Product (AUR-201) in Patients With Unilateral Microtia
NCT06078566	PHASE1/PHASE2	TERMINATED	Long-Term Follow-Up Study of Unilateral Microtia Patients Implanted With AUR-201
NCT06225336	PHASE1	TERMINATED	Subcutaneous Implant Combination Product (AUR-201) in Patients With Unilateral Microtia (Australia)
NCT00958802	EARLY_PHASE1	COMPLETED	Tissue Engineering Microtia Auricular Reconstruction: in Vitro and in Vivo Studies
NCT04230746	EARLY_PHASE1	WITHDRAWN	Effect of Antibiotics on Urinary Microbiome
NCT05929976	Not specified	RECRUITING	InterNatIonal CHildhood Leukemia Microbiome/MEtabolome Cohort
NCT06289283	Not specified	ACTIVE_NOT_RECRUITING	Microbiota in Urine and Urothelium Can be a Factor for Induction of Urinary Bladder Cancer. The Study Will Examine Urine and Bladder Cancer Tissues From Male Patients and Urine of Controls Using Whole Genomic Sequencing Techniques and 16S rRNA. The Aim is to Elucidate Role of Microbiota in Bladder
NCT06394687	Not specified	ACTIVE_NOT_RECRUITING	The Digestion of Protein Powders in Healthy Participants Using SIMBA and LIMBA Capsule
NCT06763991	Not specified	NOT_YET_RECRUITING	Safety and Efficacy of Connecting the Residual Ear to the Cartilage Scaffold in First- vs. Second-Stage Surgery
NCT07154667	Not specified	RECRUITING	Evaluation of the Auryzon™ EAR 2.0 System in Ear Reconstruction
NCT02224677	Not specified	COMPLETED	Craniofacial Microsomia: Longitudinal Outcomes in Children Pre-Kindergarten (CLOCK)
NCT03215979	Not specified	UNKNOWN	Use of Platelet-enriched Plasma During Auricular Reconstruction
NCT03624608	Not specified	TERMINATED	Evaluation of the Auryzon Devices in the Optimization of Ear and Nose Reconstruction Procedures
NCT03729427	Not specified	WITHDRAWN	Rib Microtia and the Erector Spinae Plane (ESP) Block
NCT03771066	Not specified	COMPLETED	Bisphenol A and Muscle Insulin Sensitivity
NCT04130321	Not specified	COMPLETED	Demonstration of the Prebiotic-like Effects of Camu-camu Consumption Against Obesity-related Disorders in Humans
NCT04351893	Not specified	COMPLETED	Craniofacial Microsomia: Accelerating Understanding of the Significance and Etiology
NCT04946578	Not specified	UNKNOWN	The Effect of Prebiotics on Endurance Performance
NCT05068362	Not specified	UNKNOWN	Auricular Reconstruction in Microtia by Medpor Implant Following Tissue Expansion
NCT05417360	Not specified	COMPLETED	Akkermansia and Weight Maintenance
NCT05615116	Not specified	UNKNOWN	Clinical Study on the Distribution of Digestive Tract Microbiota Before and After Ileocecal Resection in Crohn’s Disease
NCT05714566	Not specified	UNKNOWN	Research on Gut Microbiome and Metabolomics Alterations in C.Difficile Infected IBD Patients
NCT05963659	Not specified	COMPLETED	Nitrate Modulates Cognitive Impairment Via Oral Microbiota.
NCT06220994	Not specified	UNKNOWN	the Gut Microbiome and Metabolomics in Chronic Lower extreMities Threatening Ischemia
NCT06569927	Not specified	COMPLETED	Application and Effectiveness of the Perioperative Position Management Based on the ADDIE Model in Patients With Congenital Microtia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BISPHENOL A	0	1