MCID: HMF009
MIFTS: 49

Hemifacial Hyperplasia

Categories: Fetal diseases, Rare diseases

Aliases & Classifications for Hemifacial Hyperplasia

MalaCards integrated aliases for Hemifacial Hyperplasia:

Name: Hemifacial Hyperplasia 57 59
Facial Asymmetry 57 29 6
Hemifacial Hypertrophy 57 59
Facial Hemihypertrophy 57

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
hemifacial hyperplasia:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 133900
Orphanet 59 ORPHA141145
ICD10 via Orphanet 34 Q67.4
UMLS via Orphanet 74 C1399354
MedGen 42 C1399354
ICD10 33 Q67.0

Summaries for Hemifacial Hyperplasia

OMIM : 57 The criteria for the hemifacial type of congenital hypertrophy are (1) unilateral enlargement of the viscerocranium bounded superiorly by the frontal bone (not including the eye), inferiorly by the inferior border of the mandible, medially by the midline of the face, and laterally by the ear, the pinna being included within the hypertropic area, and (2) enlargement of all tissues--teeth, bone, and soft tissue--within this area (Rowe, 1962). (133900)

MalaCards based summary : Hemifacial Hyperplasia, also known as facial asymmetry, is related to saethre-chotzen syndrome and hemifacial hyperplasia with strabismus. An important gene associated with Hemifacial Hyperplasia is EFNB1 (Ephrin B1), and among its related pathways/superpathways are Developmental Biology and mTOR signalling. The drugs Acetylcholine and abobotulinumtoxinA have been mentioned in the context of this disorder. Affiliated tissues include bone, eye and skin, and related phenotypes are facial asymmetry and hypoplasia of the maxilla

Wikipedia : 76 Hemifacial hypertrophy (also termed facial hemihypertrophy,facial hemihyperplasia, or Friedreich\'s... more...

Related Diseases for Hemifacial Hyperplasia

Diseases related to Hemifacial Hyperplasia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 64)
# Related Disease Score Top Affiliating Genes
1 saethre-chotzen syndrome 30.6 FGFR2 FGFR3
2 hemifacial hyperplasia with strabismus 12.4
3 speech development, delayed, with facial asymmetry, strabismus, and transverse earlobe crease 12.1
4 facial asymmetry temporal seizures 12.1
5 diploid-triploid mosaicism 11.5
6 mehes syndrome 11.5
7 jorgenson lenz syndrome 11.3
8 craniofacial microsomia 11.3
9 torticollis 11.1
10 hemifacial microsomia 11.1
11 hemifacial microsomia with radial defects 11.1
12 silent sinus syndrome 11.1
13 klippel-feil syndrome 11.0
14 elsahy-waters syndrome 10.9
15 mental retardation, x-linked, syndromic, snyder-robinson type 10.9
16 syndromic x-linked intellectual disability snyder type 10.9
17 johnson neuroectodermal syndrome 10.8
18 microcephaly-deafness syndrome 10.8
19 aicardi-goutieres syndrome 1 10.8
20 aicardi syndrome 10.8
21 focal dermal hypoplasia 10.8
22 orofaciodigital syndrome i 10.8
23 nevus, epidermal 10.0
24 lipomatosis 9.9
25 hypertelorism 9.8 EFNB1 FGFR2
26 plagiocephaly 9.8 FGFR2 FGFR3
27 osteoglophonic dysplasia 9.8 FGFR2 FGFR3
28 luteoma 9.8 FGFR2 FGFR3
29 beare-stevenson cutis gyrata syndrome 9.8 FGFR2 FGFR3
30 jackson-weiss syndrome 9.8 FGFR2 FGFR3
31 thanatophoric dysplasia, type i 9.8 FGFR2 FGFR3
32 neurofibromatosis, type i 9.8
33 neurofibromatosis, type iv, of riccardi 9.8
34 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 9.8
35 sensorineural hearing loss 9.8
36 plexiform neurofibroma 9.8
37 neurofibroma 9.8
38 hemimegalencephaly 9.8
39 hypertropia 9.8 FGFR2 FGFR3
40 hypochondroplasia 9.7 FGFR2 FGFR3
41 exophthalmos 9.7 FGFR2 FGFR3
42 apert syndrome 9.7 FGFR2 FGFR3
43 proteus syndrome 9.7
44 gingivitis 9.7
45 intraneural perineurioma 9.7
46 perineurioma 9.7
47 meningitis 9.7
48 lacrimoauriculodentodigital syndrome 9.7 FGFR2 FGFR3
49 achondroplasia 9.7 FGFR2 FGFR3
50 crouzon syndrome 9.7 FGFR2 FGFR3

Graphical network of the top 20 diseases related to Hemifacial Hyperplasia:



Diseases related to Hemifacial Hyperplasia

Symptoms & Phenotypes for Hemifacial Hyperplasia

Symptoms via clinical synopsis from OMIM:

57
Facies:
mandibular asymmetry
maxillary hypoplasia

Teeth:
malocclusion


Clinical features from OMIM:

133900

Human phenotypes related to Hemifacial Hyperplasia:

32
# Description HPO Frequency HPO Source Accession
1 facial asymmetry 32 HP:0000324
2 hypoplasia of the maxilla 32 HP:0000327
3 dental malocclusion 32 HP:0000689

GenomeRNAi Phenotypes related to Hemifacial Hyperplasia according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased substrate adherent cell growth GR00193-A-2 8.8 FGFR2
2 Decreased substrate adherent cell growth GR00193-A-3 8.8 FGFR3 FGFR2

MGI Mouse Phenotypes related to Hemifacial Hyperplasia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.58 EFNB1 FGFR2 FGFR3
2 digestive/alimentary MP:0005381 9.54 EFNB1 FGFR2 FGFR3
3 hearing/vestibular/ear MP:0005377 9.5 FGFR2 FGFR3 EFNB1
4 limbs/digits/tail MP:0005371 9.43 EFNB1 FGFR2 FGFR3
5 no phenotypic analysis MP:0003012 9.33 EFNB1 FGFR2 FGFR3
6 respiratory system MP:0005388 9.13 EFNB1 FGFR2 FGFR3
7 vision/eye MP:0005391 8.8 EFNB1 FGFR2 FGFR3

Drugs & Therapeutics for Hemifacial Hyperplasia

Drugs for Hemifacial Hyperplasia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 26)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcholine Approved Phase 4 51-84-3 187
2 abobotulinumtoxinA Phase 4
3 Botulinum Toxins Phase 4
4 Botulinum Toxins, Type A Phase 4
5 Cholinergic Agents Phase 4
6 incobotulinumtoxinA Phase 4
7 Neuromuscular Agents Phase 4
8 Neurotransmitter Agents Phase 4
9 onabotulinumtoxinA Phase 4
10 Peripheral Nervous System Agents Phase 4
11
Chitosan Approved, Nutraceutical Phase 3 9012-76-4 71853
12 Anticholesteremic Agents Phase 3
13 Antimetabolites Phase 3
14 Chelating Agents Phase 3
15 Coagulants Phase 3
16 Hemostatics Phase 3
17 Hypolipidemic Agents Phase 3
18 Lipid Regulating Agents Phase 3
19
Iron Approved Not Applicable 7439-89-6 23925
20
Menthol Approved Not Applicable 2216-51-5 16666
21
Salicylic acid Approved, Investigational, Vet_approved 69-72-7 338
22 Ferric Compounds Not Applicable
23 Hematinics Not Applicable
24 Micronutrients Not Applicable
25 Trace Elements Not Applicable
26 Urinastatin Not Applicable

Interventional clinical trials:

(show all 12)
# Name Status NCT ID Phase Drugs
1 Comparison of Three Botulinum Neuromodulators for Management of Facial Synkinesis Completed NCT03048383 Phase 4 OnabotulinumtoxinA Injectable Product;AbobotulinumtoxinA Injectable Product;Incobotulinumtoxin A Injectable Product
2 Tricalcium Phosphate and Chitosan as Bone Regenerator Versus Autologous Graft in Surgery for Mandibular Fracture Unknown status NCT02081885 Phase 3
3 Evaluation of Navigation Assisted Reconstruction of Posttraumatic Zygomatic Deformity Completed NCT01487018 Phase 3
4 Computational Modeling for Prediction of Acoustic Changes in Vowel Production Due to Orthognathic Surgery Unknown status NCT01887977 Not Applicable
5 Craniofacial Microsomia: Longitudinal Outcomes in Children Pre-Kindergarten (CLOCK) Unknown status NCT02224677
6 Computer Assisted Orthognathic Surgery. Facial Asymmetry Completed NCT01879969 Not Applicable
7 Efficacy of Intravenous Iron Therapy in Maintaining Hemoglobin Concentration on Patients Undergoing Bimaxillary Orthognathic Surgery Recruiting NCT03094182 Not Applicable Iron Isomaltoside 1000;Normal saline
8 Accuracy of a CAD/CAM Surgical Template for Mandible Distraction Recruiting NCT03270618 Not Applicable
9 Early Crossbite Correction - a Randomized Study Recruiting NCT03353766 Not Applicable
10 Sequelae of Developmental Dysplasia of the Hip Recruiting NCT02431871
11 Comparison Between Internal and External Distractors in Osteogenesis Not yet recruiting NCT03540329 Not Applicable
12 Three Dimensional Facial Growth Analysis Not yet recruiting NCT03514563

Search NIH Clinical Center for Hemifacial Hyperplasia

Genetic Tests for Hemifacial Hyperplasia

Genetic tests related to Hemifacial Hyperplasia:

# Genetic test Affiliating Genes
1 Facial Asymmetry 29

Anatomical Context for Hemifacial Hyperplasia

MalaCards organs/tissues related to Hemifacial Hyperplasia:

41
Bone, Eye, Skin, Colon

Publications for Hemifacial Hyperplasia

Articles related to Hemifacial Hyperplasia:

(show top 50) (show all 118)
# Title Authors Year
1
Orthognathic treatment of facial asymmetry due to temporomandibular joint ankylosis. ( 29076326 )
2018
2
Association of Involutional Lower Eyelid Entropion with Reduced Upper Eyelid Position Relative to the Corneal Light Reflex: Quantification of Facial Asymmetry. ( 29342029 )
2018
3
Facial asymmetry correction with moulded helmet therapy in infants with deformational skull base plagiocephaly. ( 29221913 )
2018
4
Assessment of facial asymmetry before and after the surgical repair of cleft lip in unilateral cleft lip and palate cases. ( 28967531 )
2018
5
Congenital hemifacial hyperplasia. ( 29402434 )
2018
6
Three-dimensional Photogrammetric Analysis of Facial Soft-to-Hard Tissue Ratios After Bimaxillary Surgery in Facial Asymmetry Patients With and Without Sturge-Weber Syndrome. ( 29794508 )
2018
7
Comparison of changes in the transverse dental axis between patients with skeletal Class III malocclusion and facial asymmetry treated by orthognathic surgery with and without presurgical orthodontic treatment. ( 28670567 )
2017
8
Targeted presurgical decompensation in patients with yaw-dependent facial asymmetry. ( 28523246 )
2017
9
Computer-assisted surgical planning and simulation for unilateral condylar benign lesions causing facial asymmetry. ( 28153564 )
2017
10
Dynamic facial asymmetry in patients with repaired cleft lip using 4D imaging (video stereophotogrammetry). ( 28011182 )
2017
11
Facial asymmetry in head and neck rhabdomyosarcoma survivors. ( 28423221 )
2017
12
Condylectomy and "surgery first" approach: An expedited treatment for condylar hyperplasia in a patient with facial asymmetry. ( 28902254 )
2017
13
Hemifacial Hyperplasia. ( 28839423 )
2017
14
The accuracy of three-dimensional prediction of soft tissue changes following the surgical correction of facial asymmetry: An innovative concept. ( 28545805 )
2017
15
Subjective and objective evaluation of frontal smile esthetics in patients with facial asymmetry-a comparative cross-sectional study. ( 27862935 )
2017
16
Orthodontic-surgical retreatment of facial asymmetry with occlusal cant and severe root resorption: A 3-year follow-up. ( 28760289 )
2017
17
The Precise Repositioning Instrument for Genioplasty and a Three-Dimensional Printing Technique for Treatment of Complex Facial Asymmetry. ( 28409207 )
2017
18
Assessment for facial nerve paralysis based on facial asymmetry. ( 29090419 )
2017
19
Facial asymmetry in patients with hemifacial spasm before and after botulinum toxin A treatment. ( 27431279 )
2016
20
Patient-Specific Implant for Residual Facial Asymmetry following Orthognathic Surgery in Unilateral Craniofacial Microsomia. ( 27516845 )
2016
21
Congenital Hemifacial Hyperplasia: Clinical Presentation and Literature Review. ( 27843653 )
2016
22
Quantitative Assessment of Facial Asymmetry Using Three-Dimensional Surface Imaging in Adults: Validating the Precision and Repeatability of a Global Approach. ( 25489769 )
2016
23
Bimaxillary Orthognathic Approach to Correct Skeletal Facial Asymmetry of Hemifacial Microsomia in Adults. ( 26908014 )
2016
24
Morphologic Analysis of the Temporomandibular Joint Between Patients With Facial Asymmetry and Asymptomatic Subjects by 2D and 3D Evaluation: A Preliminary Study. ( 27043669 )
2016
25
Evaluation of mandibular contour in patients with significant facial asymmetry. ( 26976218 )
2016
26
Progressive facial asymmetry resulting from condylar osteochondroma - A case report detailing the resection, subsequent orthognathic intervention and custom joint replacement. ( 26258023 )
2015
27
Facial asymmetry: a case report of localized linear scleroderma patient with muscular strain and spasm. ( 26413496 )
2015
28
Prostaglandin-Associated Periorbital Lipodystrophy in Cosmetic Eyelid Surgery: A Novel Cause of Facial Asymmetry. ( 26374814 )
2015
29
Facial asymmetry and genetic ancestry in Latin American admixed populations. ( 25582401 )
2015
30
Facial asymmetry in young adults with condylar hyperplasia-unusual changes in the facial bones. ( 25738093 )
2015
31
Missense mutation in the PTEN promoter of a patient with hemifacial hyperplasia. ( 26229595 )
2015
32
Three-dimensional analysis of cranial and facial asymmetry after helmet therapy for positional plagiocephaly. ( 25771922 )
2015
33
Comparison of the mandibular hinge axis in adult patients with facial asymmetry with and without posterior unilateral crossbite. ( 25150274 )
2015
34
Computer-assisted planning and navigation for the treatment of true hemifacial hyperplasia. ( 25759928 )
2015
35
Facial Asymmetry in Children with Unicoronal Synostosis Who Have Undergone Craniofacial Reconstruction in Infancy. ( 26418148 )
2015
36
Rib Bone Graft Adjusted to Fit the Facial Asymmetry: A Frame Structure Graft. ( 26468802 )
2015
37
Gingival enlargement in partial hemifacial hyperplasia. ( 25624636 )
2014
38
Modified basal osteotomy combined with osteogenic distraction (Hemi-Wing distraction) for correction of facial asymmetry: A new technique. ( 25593870 )
2014
39
Distraction osteogenesis in complex facial asymmetry corrections. ( 25203568 )
2014
40
Factors contributing to facial asymmetry in identical twins. ( 25357025 )
2014
41
Use of the matching optimal symmetry plane method in planning surgical correction of facial asymmetry--a preliminary report of 20 patients. ( 24742699 )
2014
42
One-stage treatment to osteochondroma of the coronoid process and secondary facial asymmetry with coronoidectomy and reduction malarplasty: a case report and literature review. ( 25109586 )
2014
43
On facial asymmetry and self-perception. ( 24867747 )
2014
44
Craniofacial fibrous dysplasia with facial asymmetry, canted occlusion and open bite: a case report with 2 years follow-up. ( 25707839 )
2014
45
3-Dimensional analysis for class III malocclusion patients with facial asymmetry. ( 24471038 )
2013
46
The Use of a Bioadhesive (BioGlue(Ar)) Secured Conchal Graft and Mandibular Distraction Osteogenesis to Correct Pediatric Facial Asymmetry as Result of Unilateral Temporomandibular Joint Ankylosis. ( 24436736 )
2013
47
Three dimensional evaluation of facial asymmetry after mandibular reconstruction: validation of a new method using stereophotogrammetry. ( 22939875 )
2013
48
Contralateral botulinum toxin injection to improve facial asymmetry after acute facial paralysis. ( 23444480 )
2013
49
Facial asymmetry: silent sinus syndrome. ( 23833097 )
2013
50
Clinical and imaging findings of true hemifacial hyperplasia. ( 24349801 )
2013

Variations for Hemifacial Hyperplasia

ClinVar genetic disease variations for Hemifacial Hyperplasia:

6
(show all 15)
# Gene Variation Type Significance SNP ID Assembly Location
1 FGFR2 NM_000141.4(FGFR2): c.1040C> G (p.Ser347Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121918494 GRCh37 Chromosome 10, 123276877: 123276877
2 FGFR2 NM_000141.4(FGFR2): c.1040C> G (p.Ser347Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121918494 GRCh38 Chromosome 10, 121517363: 121517363
3 FGFR3 NM_000142.4(FGFR3): c.749C> G (p.Pro250Arg) single nucleotide variant Pathogenic rs4647924 GRCh37 Chromosome 4, 1803571: 1803571
4 FGFR3 NM_000142.4(FGFR3): c.749C> G (p.Pro250Arg) single nucleotide variant Pathogenic rs4647924 GRCh38 Chromosome 4, 1801844: 1801844
5 Translocation Likely pathogenic
6 46;XY;t(1;3)(p22;q21)dn Translocation Uncertain significance
7 46;XY;t(1;2)(p34.2;q35)dn Translocation Pathogenic
8 46;XY;t(12;14)(q15;q13)mat Translocation Uncertain significance
9 46;XY;t(2;19)(q12;p13.2)dn Translocation Uncertain significance
10 46;XY;t(10;17)(p13;q23)dn Translocation Uncertain significance
11 PIK3CA NM_006218.3(PIK3CA): c.1059+12T> A single nucleotide variant Uncertain significance rs200627037 GRCh38 Chromosome 3, 179203801: 179203801
12 PIK3CA NM_006218.3(PIK3CA): c.1059+12T> A single nucleotide variant Uncertain significance rs200627037 GRCh37 Chromosome 3, 178921589: 178921589
13 SMARCA4 NM_001128849.1(SMARCA4): c.1358C> T (p.Thr453Ile) single nucleotide variant Likely benign rs1057518862 GRCh38 Chromosome 19, 10991262: 10991262
14 SMARCA4 NM_001128849.1(SMARCA4): c.1358C> T (p.Thr453Ile) single nucleotide variant Likely benign rs1057518862 GRCh37 Chromosome 19, 11101938: 11101938
15 EFNB1 GRCh37/hg19 Xq13.1(chrX: 68058460-68059931) copy number loss Pathogenic GRCh37 Chromosome X, 68058460: 68059931

Expression for Hemifacial Hyperplasia

Search GEO for disease gene expression data for Hemifacial Hyperplasia.

Pathways for Hemifacial Hyperplasia

Pathways related to Hemifacial Hyperplasia according to GeneCards Suite gene sharing:

(show all 15)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.91 EFNB1 FGFR2 FGFR3
2
Show member pathways
11.95 FGFR2 FGFR3
3 11.92 FGFR2 FGFR3
4
Show member pathways
11.78 FGFR2 FGFR3
5
Show member pathways
11.73 FGFR2 FGFR3
6 11.67 FGFR2 FGFR3
7
Show member pathways
11.66 FGFR2 FGFR3
8 11.58 FGFR2 FGFR3
9
Show member pathways
11.55 FGFR2 FGFR3
10 11.41 FGFR2 FGFR3
11 11.3 EFNB1 FGFR2 FGFR3
12 11.13 FGFR2 FGFR3
13 10.91 FGFR2 FGFR3
14 10.78 FGFR2 FGFR3
15 10.75 EFNB1 FGFR2 FGFR3

GO Terms for Hemifacial Hyperplasia

Cellular components related to Hemifacial Hyperplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of plasma membrane GO:0005887 9.13 EFNB1 FGFR2 FGFR3
2 receptor complex GO:0043235 8.62 FGFR2 FGFR3

Biological processes related to Hemifacial Hyperplasia according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.71 EFNB1 FGFR2 FGFR3
2 cell differentiation GO:0030154 9.67 EFNB1 FGFR2 FGFR3
3 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.58 FGFR2 FGFR3
4 protein autophosphorylation GO:0046777 9.57 FGFR2 FGFR3
5 peptidyl-tyrosine phosphorylation GO:0018108 9.56 FGFR2 FGFR3
6 positive regulation of protein kinase B signaling GO:0051897 9.55 FGFR2 FGFR3
7 positive regulation of MAPK cascade GO:0043410 9.52 FGFR2 FGFR3
8 negative regulation of signal transduction GO:0009968 9.51 FGFR2 FGFR3
9 phosphatidylinositol phosphorylation GO:0046854 9.48 FGFR2 FGFR3
10 fibroblast growth factor receptor signaling pathway GO:0008543 9.46 FGFR2 FGFR3
11 positive regulation of kinase activity GO:0033674 9.43 FGFR2 FGFR3
12 phosphatidylinositol-3-phosphate biosynthetic process GO:0036092 9.4 FGFR2 FGFR3
13 bone mineralization GO:0030282 9.37 FGFR2 FGFR3
14 cell-cell signaling GO:0007267 9.33 EFNB1 FGFR2 FGFR3
15 bone morphogenesis GO:0060349 9.32 FGFR2 FGFR3
16 embryonic pattern specification GO:0009880 9.26 EFNB1 FGFR2
17 positive regulation of phospholipase activity GO:0010518 8.96 FGFR2 FGFR3
18 endochondral bone growth GO:0003416 8.62 FGFR2 FGFR3

Molecular functions related to Hemifacial Hyperplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein tyrosine kinase activity GO:0004713 9.46 FGFR2 FGFR3
2 Ras guanyl-nucleotide exchange factor activity GO:0005088 9.43 FGFR2 FGFR3
3 MAP kinase kinase kinase activity GO:0004709 9.4 FGFR2 FGFR3
4 mitogen-activated protein kinase kinase binding GO:0031434 9.37 FGFR2 FGFR3
5 phosphatidylinositol-4,5-bisphosphate 3-kinase activity GO:0046934 9.32 FGFR2 FGFR3
6 transmembrane receptor protein tyrosine kinase activity GO:0004714 9.26 FGFR2 FGFR3
7 1-phosphatidylinositol-3-kinase activity GO:0016303 9.16 FGFR2 FGFR3
8 fibroblast growth factor binding GO:0017134 8.96 FGFR2 FGFR3
9 fibroblast growth factor-activated receptor activity GO:0005007 8.62 FGFR2 FGFR3

Sources for Hemifacial Hyperplasia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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