MCID: PST049
MIFTS: 46

Postaxial Acrofacial Dysostosis

Categories: Genetic diseases, Rare diseases, Eye diseases, Bone diseases, Fetal diseases

Aliases & Classifications for Postaxial Acrofacial Dysostosis

MalaCards integrated aliases for Postaxial Acrofacial Dysostosis:

Name: Postaxial Acrofacial Dysostosis 57 25 59 75
Miller Syndrome 57 53 25 59 75 29 13 6 40
Genee-Wiedemann Syndrome 57 53 25 73
Poads 57 59 75 55
Genee-Wiedemann Acrofacial Dysostosis 53 25
Mandibulfacial Dysostosis with Postaxial Limb Anomalies 59
Postaxial Acrofacial Dysostosis Syndrome 53
Acrofacial Dysostosis, Genee-Wiedmann Type 59
Chromosome 11p Deletion Syndrome 73
Wildervanck-Smith Syndrome 53
Postaxial Acrodysostosis 59
Poads Syndrome 53
Gwafd 53

Characteristics:

Orphanet epidemiological data:

59
postaxial acrofacial dysostosis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
most cases are sporadic
autosomal recessive and dominant pedigrees described


HPO:

32
postaxial acrofacial dysostosis:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Postaxial Acrofacial Dysostosis

NIH Rare Diseases : 53 Miller syndrome is a rare condition that mainly affects the development of the face and limbs. Characteristic features include underdeveloped cheek bones, a very small lower jaw, cleft lip and/or palate, abnormalities of the eyes, absent fifth (pinky) fingers and toes, and abnormally formed bones in the forearms and lower legs. The severity of the disorder varies among affected individuals. Miller syndrome is caused by mutations in the DHODH gene. It is inherited in an autosomal recessive manner.

MalaCards based summary : Postaxial Acrofacial Dysostosis, also known as miller syndrome, is related to say barber miller syndrome and acrofacial dysostosis 1, nager type. An important gene associated with Postaxial Acrofacial Dysostosis is DHODH (Dihydroorotate Dehydrogenase (Quinone)), and among its related pathways/superpathways are Formation of Fibrin Clot (Clotting Cascade) and Complement and coagulation cascades. The drugs Hemostatics and Liver Extracts have been mentioned in the context of this disorder. Affiliated tissues include bone, eye and kidney, and related phenotypes are malar flattening and finger syndactyly

OMIM : 57 Miller syndrome, or postaxial acrofacial dysostosis, is a rare autosomal recessive disorder characterized clinically by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the postaxial elements of the limbs, coloboma of the eyelids, and supernumerary nipples (summary by Ng et al., 2010). (263750)

UniProtKB/Swiss-Prot : 75 Postaxial acrofacial dysostosis: POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases.

Genetics Home Reference : 25 Miller syndrome is a rare condition that mainly affects the development of the face and limbs. The severity of this disorder varies among affected individuals.

Wikipedia : 76 Miller syndrome is a genetic condition also known as the Genee–Wiedemann syndrome, Wildervanck–Smith... more...

Related Diseases for Postaxial Acrofacial Dysostosis

Graphical network of the top 20 diseases related to Postaxial Acrofacial Dysostosis:



Diseases related to Postaxial Acrofacial Dysostosis

Symptoms & Phenotypes for Postaxial Acrofacial Dysostosis

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears
conductive hearing loss
cup-shaped ears

Head And Neck Mouth:
cleft palate
cleft lip

GenitourinaryInternal GenitaliaMale:
cryptorchidism

Skeletal Limbs:
radioulnar synostosis
radial hypoplasia
ulnar hypoplasia
in-curving forearms

Head And Neck Eyes:
ectropion
eyelid coloboma
downslanting palpebral fissure

Skeletal Pelvis:
congenital hip dislocation

Chest Breasts:
accessory nipples

Skeletal Skull:
malar hypoplasia

Growth Other:
postnatal growth deficiency

Skeletal Feet:
absence of fifth digit

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum
rib defects

Head And Neck Face:
micrognathia

Head And Neck Nose:
choanal atresia

Abdomen Gastrointestinal:
pyloric stenosis
midgut malrotation

Genitourinary External Genitalia Male:
micropenis

Skeletal Hands:
syndactyly
thumb hypoplasia
absence of fifth digit

Head And Neck Teeth:
conical teeth

Genitourinary Kidneys:
renal anomalies

Skeletal Spine:
supernumerary vertebrae


Clinical features from OMIM:

263750

Human phenotypes related to Postaxial Acrofacial Dysostosis:

59 32 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 malar flattening 59 32 hallmark (90%) Very frequent (99-80%) HP:0000272
2 finger syndactyly 59 32 frequent (33%) Frequent (79-30%) HP:0006101
3 microtia 59 32 hallmark (90%) Very frequent (99-80%) HP:0008551
4 cleft palate 59 32 frequent (33%) Frequent (79-30%) HP:0000175
5 micrognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000347
6 strabismus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000486
7 abnormal dermatoglyphics 59 32 hallmark (90%) Very frequent (99-80%) HP:0007477
8 non-midline cleft lip 59 32 frequent (33%) Frequent (79-30%) HP:0100335
9 low-set, posteriorly rotated ears 59 32 hallmark (90%) Very frequent (99-80%) HP:0000368
10 downslanted palpebral fissures 59 32 hallmark (90%) Very frequent (99-80%) HP:0000494
11 conductive hearing impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000405
12 camptodactyly of finger 59 32 frequent (33%) Frequent (79-30%) HP:0100490
13 hypoplasia of the ulna 59 32 hallmark (90%) Very frequent (99-80%) HP:0003022
14 supernumerary nipple 59 32 hallmark (90%) Very frequent (99-80%) HP:0002558
15 hypoplasia of the radius 59 32 hallmark (90%) Very frequent (99-80%) HP:0002984
16 cupped ear 59 32 hallmark (90%) Very frequent (99-80%) HP:0000378
17 ectropion of lower eyelids 59 32 hallmark (90%) Very frequent (99-80%) HP:0007651
18 low-set ears 32 HP:0000369
19 pectus excavatum 32 HP:0000767
20 malformation of the heart and great vessels 59 Frequent (79-30%)
21 cryptorchidism 32 HP:0000028
22 growth delay 32 HP:0001510
23 postnatal growth retardation 32 HP:0008897
24 abnormality of the foot 32 HP:0001760
25 abnormality of the kidney 32 HP:0000077
26 choanal atresia 32 HP:0000453
27 radioulnar synostosis 32 HP:0002974
28 pyloric stenosis 32 HP:0002021
29 cleft upper lip 32 HP:0000204
30 ectropion 32 HP:0000656
31 abnormality of cardiovascular system morphology 32 frequent (33%) HP:0030680
32 abnormality of the middle ear 59 Frequent (79-30%)
33 cleft eyelid 59 Very frequent (99-80%)
34 micropenis 32 HP:0000054
35 congenital hip dislocation 32 HP:0001374
36 syndactyly 32 HP:0001159
37 conical tooth 32 HP:0000698
38 short thumb 32 HP:0009778
39 midgut malrotation 32 HP:0005211
40 eyelid coloboma 32 hallmark (90%) HP:0000625
41 supernumerary vertebrae 32 HP:0002946

Drugs & Therapeutics for Postaxial Acrofacial Dysostosis

Drugs for Postaxial Acrofacial Dysostosis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Hemostatics Not Applicable
2 Liver Extracts

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Genetic Analysis of Oculocerebrorenal Syndrome of Lowe Completed NCT00359515
2 Study of the Pathophysiological Mechanisms Involved in Bleeding Events Completed NCT01314560 Not Applicable
3 Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing Recruiting NCT03065686 Not Applicable
4 Prospective Research Rare Kidney Stones (ProRKS) Recruiting NCT02780297
5 Clinical and Molecular Investigations Into Ciliopathies Active, not recruiting NCT00068224

Search NIH Clinical Center for Postaxial Acrofacial Dysostosis

Genetic Tests for Postaxial Acrofacial Dysostosis

Genetic tests related to Postaxial Acrofacial Dysostosis:

# Genetic test Affiliating Genes
1 Miller Syndrome 29 DHODH

Anatomical Context for Postaxial Acrofacial Dysostosis

MalaCards organs/tissues related to Postaxial Acrofacial Dysostosis:

41
Bone, Eye, Kidney, Liver, Heart

Publications for Postaxial Acrofacial Dysostosis

Articles related to Postaxial Acrofacial Dysostosis:

(show all 26)
# Title Authors Year
1
Elevated plasma dihydroorotate in Miller syndrome: Biochemical, diagnostic and clinical implications, and treatment with uridine. ( 27370710 )
2016
2
Orodental findings in postaxial acrofacial dysostosis. ( 24959059 )
2014
3
Protein instability and functional defects caused by mutations of dihydro-orotate dehydrogenase in Miller syndrome patients. ( 22967083 )
2012
4
Miller (Genee-Wiedemann) syndrome represents a clinically and biochemically distinct subgroup of postaxial acrofacial dysostosis associated with partial deficiency of DHODH. ( 22692683 )
2012
5
Miller syndrome with novel dihydroorotate dehydrogenase gene mutations. ( 21851494 )
2011
6
Extra phenotypic features in a girl with Miller syndrome. ( 21346561 )
2011
7
A variant or a &amp;quot;new&amp;quot; postaxial acrofacial dysostosis syndrome. ( 18286304 )
2008
8
Postaxial acrofacial dysostosis syndrome with vertebral segmentation defects. ( 8055139 )
1994
9
Miller postaxial acrofacial dysostosis. The phenotypic changes with age. ( 8357564 )
1993
10
Miller postaxial acrofacial dysostosis syndrome. Follow-up data of a family and confirmation of autosomal recessive inheritance. ( 8375109 )
1993
11
Postaxial acrofacial dysostosis: report on two patients. ( 1488973 )
1992
12
Familial postaxial acrofacial dysostosis syndrome. ( 1433242 )
1992
13
Postaxial acrofacial dysostosis (Miller) syndrome: a new case. ( 1683410 )
1991
14
Miller syndrome (postaxial acrofacial dysostosis): further evidence for autosomal recessive inheritance and expansion of the phenotype. ( 1941965 )
1991
15
New form of postaxial acrofacial dysostosis? ( 1776633 )
1991
16
Severe postaxial acrofacial dysostosis: an anatomic and angiographic study. ( 2333876 )
1990
17
Postaxial acrofacial dysostosis: report of a Brazilian patient. ( 2596501 )
1989
18
Atypical postaxial acrofacial dysostosis (AFD): diabetic embryopathy or a new AFD syndrome? ( 2596502 )
1989
19
Postaxial acrofacial dysostosis or Miller syndrome. A case report. ( 2920751 )
1989
20
Postaxial acrofacial dysostosis syndrome with microcephaly, seizures and profound mental retardation. ( 3228151 )
1988
21
Miller's syndrome. Anaesthetic management of postaxial acrofacial dysostosis. ( 3661933 )
1987
22
Nager &amp;quot;syndrome&amp;quot; versus &amp;quot;anomaly&amp;quot; and its nosology with the postaxial acrofacial dysostosis syndrome of GenAce and Wiedemann. ( 3425605 )
1987
23
Postaxial acrofacial dysostosis (Miller) syndrome. ( 3612717 )
1987
24
Robin sequence and oligodactyly in mother and son--probably a further example of the postaxial acrofacial dysostosis syndrome. ( 3425604 )
1987
25
Recurrence of the postaxial acrofacial dysostosis syndrome in a sibship: implications for genetic counseling. ( 7452413 )
1981
26
Postaxial acrofacial dysostosis syndrome. ( 501501 )
1979

Variations for Postaxial Acrofacial Dysostosis

UniProtKB/Swiss-Prot genetic disease variations for Postaxial Acrofacial Dysostosis:

75
# Symbol AA change Variation ID SNP ID
1 DHODH p.Gly19Glu VAR_062412 rs267606765
2 DHODH p.Arg135Cys VAR_062413 rs201230446
3 DHODH p.Gly152Arg VAR_062414 rs267606766
4 DHODH p.Arg199Cys VAR_062415 rs267606769
5 DHODH p.Gly202Ala VAR_062416 rs267606767
6 DHODH p.Gly202Asp VAR_062417 rs267606767
7 DHODH p.Arg244Trp VAR_062418 rs267606768
8 DHODH p.Thr284Ile VAR_062419
9 DHODH p.Arg346Trp VAR_062420 rs201947120
10 DHODH p.Asp392Gly VAR_062421 rs779076692

ClinVar genetic disease variations for Postaxial Acrofacial Dysostosis:

6
(show top 50) (show all 111)
# Gene Variation Type Significance SNP ID Assembly Location
1 DHODH NM_001361.4(DHODH): c.1036C> T (p.Arg346Trp) single nucleotide variant Pathogenic rs201947120 GRCh37 Chromosome 16, 72057435: 72057435
2 DHODH NM_001361.4(DHODH): c.1036C> T (p.Arg346Trp) single nucleotide variant Pathogenic rs201947120 GRCh38 Chromosome 16, 72023536: 72023536
3 DHODH NM_001361.4(DHODH): c.403C> T (p.Arg135Cys) single nucleotide variant Pathogenic/Likely pathogenic rs201230446 GRCh37 Chromosome 16, 72048540: 72048540
4 DHODH NM_001361.4(DHODH): c.403C> T (p.Arg135Cys) single nucleotide variant Pathogenic/Likely pathogenic rs201230446 GRCh38 Chromosome 16, 72014641: 72014641
5 DHODH NM_001361.4(DHODH): c.454G> A (p.Gly152Arg) single nucleotide variant Pathogenic rs267606766 GRCh37 Chromosome 16, 72050942: 72050942
6 DHODH NM_001361.4(DHODH): c.454G> A (p.Gly152Arg) single nucleotide variant Pathogenic rs267606766 GRCh38 Chromosome 16, 72017043: 72017043
7 DHODH NM_001361.4(DHODH): c.605G> C (p.Gly202Ala) single nucleotide variant Pathogenic rs267606767 GRCh37 Chromosome 16, 72055110: 72055110
8 DHODH NM_001361.4(DHODH): c.605G> C (p.Gly202Ala) single nucleotide variant Pathogenic rs267606767 GRCh38 Chromosome 16, 72021211: 72021211
9 DHODH NM_001361.4(DHODH): c.605G> A (p.Gly202Asp) single nucleotide variant Pathogenic rs267606767 GRCh37 Chromosome 16, 72055110: 72055110
10 DHODH NM_001361.4(DHODH): c.605G> A (p.Gly202Asp) single nucleotide variant Pathogenic rs267606767 GRCh38 Chromosome 16, 72021211: 72021211
11 DHODH NM_001361.4(DHODH): c.730C> T (p.Arg244Trp) single nucleotide variant Pathogenic rs267606768 GRCh37 Chromosome 16, 72056285: 72056285
12 DHODH NM_001361.4(DHODH): c.730C> T (p.Arg244Trp) single nucleotide variant Pathogenic rs267606768 GRCh38 Chromosome 16, 72022386: 72022386
13 DHODH DHODH, 1-BP DEL, 611T deletion Pathogenic
14 DHODH NM_001361.4(DHODH): c.595C> T (p.Arg199Cys) single nucleotide variant Pathogenic rs267606769 GRCh37 Chromosome 16, 72055100: 72055100
15 DHODH NM_001361.4(DHODH): c.595C> T (p.Arg199Cys) single nucleotide variant Pathogenic rs267606769 GRCh38 Chromosome 16, 72021201: 72021201
16 DHODH NM_001361.4(DHODH): c.294C> T (p.Asp98=) single nucleotide variant Uncertain significance rs61747639 GRCh37 Chromosome 16, 72048431: 72048431
17 DHODH NM_001361.4(DHODH): c.294C> T (p.Asp98=) single nucleotide variant Uncertain significance rs61747639 GRCh38 Chromosome 16, 72014532: 72014532
18 DHODH NM_001361.4(DHODH): c.573G> A (p.Ala191=) single nucleotide variant Uncertain significance rs148523165 GRCh37 Chromosome 16, 72055078: 72055078
19 DHODH NM_001361.4(DHODH): c.573G> A (p.Ala191=) single nucleotide variant Uncertain significance rs148523165 GRCh38 Chromosome 16, 72021179: 72021179
20 DHODH NM_001361.4(DHODH): c.72C> T (p.Phe24=) single nucleotide variant Uncertain significance rs61753576 GRCh38 Chromosome 16, 72012100: 72012100
21 DHODH NM_001361.4(DHODH): c.72C> T (p.Phe24=) single nucleotide variant Uncertain significance rs61753576 GRCh37 Chromosome 16, 72045999: 72045999
22 DHODH NM_001361.4(DHODH): c.457C> A (p.Leu153Ile) single nucleotide variant Uncertain significance rs61741731 GRCh38 Chromosome 16, 72017046: 72017046
23 DHODH NM_001361.4(DHODH): c.457C> A (p.Leu153Ile) single nucleotide variant Uncertain significance rs61741731 GRCh37 Chromosome 16, 72050945: 72050945
24 DHODH NM_001361.4(DHODH): c.890G> A (p.Arg297His) single nucleotide variant Uncertain significance rs200181357 GRCh37 Chromosome 16, 72057134: 72057134
25 DHODH NM_001361.4(DHODH): c.890G> A (p.Arg297His) single nucleotide variant Uncertain significance rs200181357 GRCh38 Chromosome 16, 72023235: 72023235
26 DHODH NM_001361.4(DHODH): c.959A> G (p.Tyr320Cys) single nucleotide variant Uncertain significance rs886052279 GRCh38 Chromosome 16, 72023304: 72023304
27 DHODH NM_001361.4(DHODH): c.959A> G (p.Tyr320Cys) single nucleotide variant Uncertain significance rs886052279 GRCh37 Chromosome 16, 72057203: 72057203
28 DHODH NM_001361.4(DHODH): c.*139C> T single nucleotide variant Uncertain significance rs140263128 GRCh38 Chromosome 16, 72024338: 72024338
29 DHODH NM_001361.4(DHODH): c.*139C> T single nucleotide variant Uncertain significance rs140263128 GRCh37 Chromosome 16, 72058237: 72058237
30 DHODH NM_001361.4(DHODH): c.*252C> T single nucleotide variant Uncertain significance rs147792232 GRCh37 Chromosome 16, 72058350: 72058350
31 DHODH NM_001361.4(DHODH): c.*252C> T single nucleotide variant Uncertain significance rs147792232 GRCh38 Chromosome 16, 72024451: 72024451
32 DHODH NM_001361.4(DHODH): c.*783A> G single nucleotide variant Benign rs2288000 GRCh38 Chromosome 16, 72024982: 72024982
33 DHODH NM_001361.4(DHODH): c.*783A> G single nucleotide variant Benign rs2288000 GRCh37 Chromosome 16, 72058881: 72058881
34 DHODH NM_001361.4(DHODH): c.*1035_*1038delTTCT deletion Uncertain significance rs886052283 GRCh38 Chromosome 16, 72025234: 72025237
35 DHODH NM_001361.4(DHODH): c.*1035_*1038delTTCT deletion Uncertain significance rs886052283 GRCh37 Chromosome 16, 72059133: 72059136
36 DHODH NM_001361.4(DHODH): c.*1174T> G single nucleotide variant Uncertain significance rs148338434 GRCh38 Chromosome 16, 72025373: 72025373
37 DHODH NM_001361.4(DHODH): c.*1174T> G single nucleotide variant Uncertain significance rs148338434 GRCh37 Chromosome 16, 72059272: 72059272
38 DHODH NM_001361.4(DHODH): c.819+10G> A single nucleotide variant Likely benign rs114267707 GRCh38 Chromosome 16, 72022485: 72022485
39 DHODH NM_001361.4(DHODH): c.22-11C> T single nucleotide variant Uncertain significance rs770515591 GRCh38 Chromosome 16, 72012039: 72012039
40 DHODH NM_001361.4(DHODH): c.22-11C> T single nucleotide variant Uncertain significance rs770515591 GRCh37 Chromosome 16, 72045938: 72045938
41 DHODH NM_001361.4(DHODH): c.154G> C (p.Glu52Gln) single nucleotide variant Uncertain significance rs368395651 GRCh38 Chromosome 16, 72012182: 72012182
42 DHODH NM_001361.4(DHODH): c.154G> C (p.Glu52Gln) single nucleotide variant Uncertain significance rs368395651 GRCh37 Chromosome 16, 72046081: 72046081
43 DHODH NM_001361.4(DHODH): c.492G> T (p.Gln164His) single nucleotide variant Uncertain significance rs768224976 GRCh38 Chromosome 16, 72017081: 72017081
44 DHODH NM_001361.4(DHODH): c.492G> T (p.Gln164His) single nucleotide variant Uncertain significance rs768224976 GRCh37 Chromosome 16, 72050980: 72050980
45 DHODH NM_001361.4(DHODH): c.666C> G (p.Ser222Arg) single nucleotide variant Uncertain significance rs528598713 GRCh38 Chromosome 16, 72021272: 72021272
46 DHODH NM_001361.4(DHODH): c.666C> G (p.Ser222Arg) single nucleotide variant Uncertain significance rs528598713 GRCh37 Chromosome 16, 72055171: 72055171
47 DHODH NM_001361.4(DHODH): c.753C> A (p.Val251=) single nucleotide variant Uncertain significance rs373893426 GRCh38 Chromosome 16, 72022409: 72022409
48 DHODH NM_001361.4(DHODH): c.753C> A (p.Val251=) single nucleotide variant Uncertain significance rs373893426 GRCh37 Chromosome 16, 72056308: 72056308
49 DHODH NM_001361.4(DHODH): c.807T> A (p.Ser269Arg) single nucleotide variant Uncertain significance rs886052277 GRCh38 Chromosome 16, 72022463: 72022463
50 DHODH NM_001361.4(DHODH): c.807T> A (p.Ser269Arg) single nucleotide variant Uncertain significance rs886052277 GRCh37 Chromosome 16, 72056362: 72056362

Expression for Postaxial Acrofacial Dysostosis

Search GEO for disease gene expression data for Postaxial Acrofacial Dysostosis.

Pathways for Postaxial Acrofacial Dysostosis

GO Terms for Postaxial Acrofacial Dysostosis

Biological processes related to Postaxial Acrofacial Dysostosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 blood coagulation GO:0007596 8.96 PLAT THBD
2 female pregnancy GO:0007565 8.62 DHODH THBD

Sources for Postaxial Acrofacial Dysostosis

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
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44 MeSH
45 MESH via Orphanet
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49 NCI
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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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