MCID: AXN009
MIFTS: 49

Axenfeld-Rieger Syndrome, Type 1

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

Aliases & Classifications for Axenfeld-Rieger Syndrome, Type 1

MalaCards integrated aliases for Axenfeld-Rieger Syndrome, Type 1:

Name: Axenfeld-Rieger Syndrome, Type 1 53 13 69
Axenfeld-Rieger Syndrome Type 1 12 28 14
Rieg1 53 12 71
Rieg 53 71 51
Rieger Syndrome Type 1 12 71
Rgs 53 71
Iridogoniodysgenesis with Somatic Anomalies 71
Axenfeld-Rieger Syndrome 1 71
Rieger Syndrome, Type 1 53

Characteristics:

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
variable expressivity
genetic heterogeneity (see rieg2, )


HPO:

31
axenfeld-rieger syndrome, type 1:
Onset and clinical course variable expressivity
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Axenfeld-Rieger Syndrome, Type 1

OMIM : 53 Axenfeld-Rieger syndrome is an autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals (Fitch and Kaback, 1978). Systemic anomalies are associated, including dental hypoplasia, failure of involution of periumbilical skin, and maxillary hypoplasia (Alkemade, 1969). (180500)

MalaCards based summary : Axenfeld-Rieger Syndrome, Type 1, also known as axenfeld-rieger syndrome type 1, is related to axenfeld-rieger syndrome and peters-plus syndrome, and has symptoms including prominent supraorbital ridges, wide nasal bridge and strabismus. An important gene associated with Axenfeld-Rieger Syndrome, Type 1 is PITX2 (Paired Like Homeodomain 2), and among its related pathways/superpathways are Mesodermal Commitment Pathway and Ectoderm Differentiation. Affiliated tissues include skin and eye, and related phenotypes are cardiovascular system and endocrine/exocrine gland

UniProtKB/Swiss-Prot : 71 Axenfeld-Rieger syndrome 1: An autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals. Additional features include aniridia, maxillary hypoplasia, hypodontia, anal stenosis, redundant periumbilical skin.

Disease Ontology : 12 An Axenfeld-Rieger syndrome that has material basis in heterozygous mutation in the homeobox transcription factor gene PITX2 on chromosome 4q25.

Related Diseases for Axenfeld-Rieger Syndrome, Type 1

Diseases in the Axenfeld-Rieger Syndrome family:

Axenfeld-Rieger Syndrome, Type 1 Axenfeld-Rieger Syndrome, Type 2
Axenfeld-Rieger Syndrome, Type 3

Diseases related to Axenfeld-Rieger Syndrome, Type 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 27)
# Related Disease Score Top Affiliating Genes
1 axenfeld-rieger syndrome 32.1 PAX6 PITX2 SHOX2
2 peters-plus syndrome 30.1 PAX6 PITX2 PITX3
3 blood group, chido/rodgers system 11.5
4 axenfeld-rieger syndrome, type 2 11.0
5 fryns microphthalmia syndrome 10.3 HESX1 PAX6
6 intestinal atresia 10.2 PAX6 PITX2
7 anterior segment dysgenesis 1 10.2 PAX6 PITX2 PITX3
8 leri-weill dyschondrosteosis 10.2 SHOX SHOX2
9 scleral staphyloma 10.2 PAX2 PAX6
10 septopreoptic holoprosencephaly 10.1 FGF8 SHH
11 papillorenal syndrome 10.1 PAX2 PAX6
12 midline interhemispheric variant of holoprosencephaly 10.1 FGF8 SHH
13 microform holoprosencephaly 10.0 FGF8 SHH
14 alobar holoprosencephaly 10.0 FGF8 SHH
15 congenital aphakia 10.0 PAX2 PAX6
16 lobar holoprosencephaly 10.0 FGF8 SHH
17 iris disease 10.0 PAX6 PITX2
18 isolated growth hormone deficiency, type iii 10.0 ESX1 HESX1
19 physical disorder 9.9 FGF8 SHH SHOX2
20 anterior segment dysgenesis 4 9.9
21 semilobar holoprosencephaly 9.9 FGF8 SHH
22 eyelid disease 9.9 FOXL2 SHOX2
23 tooth size 9.8 BMP4 FGF8 SHH
24 agnathia-otocephaly complex 9.7 BMP4 FGF8 SHH
25 coloboma of macula 9.7 PAX2 PAX6 SHH
26 orofacial cleft 9.5 BMP4 FGF8 SHH SHOX2
27 microphthalmia 9.2 BMP4 PAX2 PAX6 PITX3 SHH

Graphical network of the top 20 diseases related to Axenfeld-Rieger Syndrome, Type 1:



Diseases related to Axenfeld-Rieger Syndrome, Type 1

Symptoms & Phenotypes for Axenfeld-Rieger Syndrome, Type 1

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Face:
prominent supraorbital ridges
short philtrum
maxillary hypoplasia

Genitourinary External Genitalia Male:
hypospadias

Endocrine Features:
growth hormone deficiency

Head And Neck Mouth:
thin upper lip

Abdomen External Features:
umbilical defect (redundant periumbilical skin)

Head And Neck Eyes:
strabismus
megalocornea
glaucoma
microcornea
aniridia
more
Abdomen Gastroin testinal:
anal stenosis
imperforate anus

Head And Neck Nose:
broad nasal bridge

Head And Neck Teeth:
hypodontia (maxillary incisors)


Clinical features from OMIM:

180500

Human phenotypes related to Axenfeld-Rieger Syndrome, Type 1:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 prominent supraorbital ridges 31 HP:0000336
2 wide nasal bridge 31 HP:0000431
3 strabismus 31 HP:0000486
4 megalocornea 31 HP:0000485
5 short philtrum 31 HP:0000322
6 hypospadias 31 HP:0000047
7 hypoplasia of the maxilla 31 HP:0000327
8 glaucoma 31 HP:0000501
9 hypoplasia of the iris 31 HP:0007676
10 anal atresia 31 HP:0002023
11 posterior embryotoxon 31 HP:0000627
12 thin upper lip vermilion 31 HP:0000219
13 hypodontia 31 HP:0000668
14 microcornea 31 HP:0000482
15 aniridia 31 HP:0000526
16 anal stenosis 31 HP:0002025
17 growth hormone deficiency 31 HP:0000824
18 rieger anomaly 31 HP:0000558
19 abnormality of the abdominal wall 31 HP:0004298
20 abnormally prominent line of schwalbe 31 HP:0007873
21 polycoria 31 HP:0011500

MGI Mouse Phenotypes related to Axenfeld-Rieger Syndrome, Type 1:

43 (show all 17)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.27 CRX FGF8 BMP4 PITX3 PITX1 PAX2
2 endocrine/exocrine gland MP:0005379 10.22 HESX1 FGF8 PAX2 BMP4 FOXL2 PITX1
3 growth/size/body region MP:0005378 10.21 BMP4 HESX1 FGF8 FOXL2 PITX2 PAX6
4 craniofacial MP:0005382 10.16 HESX1 FGF8 BMP4 PITX1 PITX2 PAX6
5 mortality/aging MP:0010768 10.16 FOXL2 BMP4 HESX1 FGF8 PITX2 PAX6
6 embryo MP:0005380 10.14 HESX1 FGF8 BMP4 PITX1 PAX2 PITX2
7 nervous system MP:0003631 10.14 CRX HESX1 FGF8 PAX2 BMP4 PITX3
8 digestive/alimentary MP:0005381 10.09 FGF8 BMP4 PITX2 PAX6 PITX1 SHH
9 hearing/vestibular/ear MP:0005377 10.04 HESX1 FGF8 PAX2 BMP4 PITX1 PAX6
10 limbs/digits/tail MP:0005371 9.95 FGF8 BMP4 PITX2 PITX1 SHOX2 SHH
11 muscle MP:0005369 9.91 BMP4 FGF8 PITX2 PAX6 PITX1 SHH
12 normal MP:0002873 9.91 FOXL2 BMP4 HESX1 FGF8 PITX2 PAX6
13 reproductive system MP:0005389 9.86 FGF8 BMP4 FOXL2 PITX2 PAX6 PITX3
14 pigmentation MP:0001186 9.72 CRX PITX2 PAX6 PITX3 PAX2
15 respiratory system MP:0005388 9.7 HESX1 FGF8 BMP4 PAX6 PITX3 PITX2
16 skeleton MP:0005390 9.56 FGF8 BMP4 PITX2 PAX6 PITX1 PITX3
17 vision/eye MP:0005391 9.32 HESX1 CRX FGF8 PAX2 BMP4 FOXL2

Drugs & Therapeutics for Axenfeld-Rieger Syndrome, Type 1

Search Clinical Trials , NIH Clinical Center for Axenfeld-Rieger Syndrome, Type 1

Genetic Tests for Axenfeld-Rieger Syndrome, Type 1

Genetic tests related to Axenfeld-Rieger Syndrome, Type 1:

# Genetic test Affiliating Genes
1 Axenfeld-Rieger Syndrome Type 1 28 PITX2

Anatomical Context for Axenfeld-Rieger Syndrome, Type 1

MalaCards organs/tissues related to Axenfeld-Rieger Syndrome, Type 1:

38
Skin, Eye

Publications for Axenfeld-Rieger Syndrome, Type 1

Articles related to Axenfeld-Rieger Syndrome, Type 1:

# Title Authors Year
1
A mutation in the RIEG1 gene associated with Peters' anomaly. ( 10051017 )
1999
2
Mutation in the RIEG1 gene in patients with iridogoniodysgenesis syndrome. ( 9618168 )
1998

Variations for Axenfeld-Rieger Syndrome, Type 1

UniProtKB/Swiss-Prot genetic disease variations for Axenfeld-Rieger Syndrome, Type 1:

71
# Symbol AA change Variation ID SNP ID
1 PITX2 p.Leu100Gln VAR_003763 rs104893857
2 PITX2 p.Thr114Pro VAR_003764 rs104893858
3 PITX2 p.Arg137Pro VAR_003766 rs104893859
4 PITX2 p.Val129Leu VAR_035029 rs121909249
5 PITX2 p.Pro110Leu VAR_058735 rs1057519484Axenfeld-Rieger
6 PITX2 p.Pro110Arg VAR_058736
7 PITX2 p.Lys134Glu VAR_058737 rs387906810
8 PITX2 p.Arg136Cys VAR_058738
9 PITX2 p.Leu151Val VAR_058739
10 PITX2 p.Asn154Thr VAR_058740

ClinVar genetic disease variations for Axenfeld-Rieger Syndrome, Type 1:

6 (show all 19)
# Gene Variation Type Significance SNP ID Assembly Location
1 PITX2 NM_153427.2(PITX2): c.272G> C (p.Arg91Pro) single nucleotide variant Pathogenic rs104893859 GRCh37 Chromosome 4, 111539825: 111539825
2 PITX2 NM_153427.2(PITX2): c.161T> A (p.Leu54Gln) single nucleotide variant Pathogenic rs104893857 GRCh37 Chromosome 4, 111542411: 111542411
3 PITX2 PITX2, IVS3DS, G-C, +5 single nucleotide variant Pathogenic
4 PITX2 NM_153427.2(PITX2): c.202A> C (p.Thr68Pro) single nucleotide variant Pathogenic rs104893858 GRCh37 Chromosome 4, 111542370: 111542370
5 PITX2 PITX2, IVS3AS, A-G, -11 single nucleotide variant Pathogenic
6 PITX2 NM_153427.2(PITX2): c.399G> A (p.Trp133Ter) single nucleotide variant Pathogenic rs104893860 GRCh37 Chromosome 4, 111539698: 111539698
7 PITX2 NM_153427.2(PITX2): c.247G> C (p.Val83Leu) single nucleotide variant Pathogenic rs121909249 GRCh37 Chromosome 4, 111542325: 111542325
8 PITX2 PITX2, 21-BP DUP, NT713 duplication Pathogenic
9 PITX2 NM_153427.2(PITX2): c.262A> G (p.Lys88Glu) single nucleotide variant Pathogenic rs387906810 GRCh37 Chromosome 4, 111539835: 111539835
10 PITX2 NM_153427.2(PITX2): c.184_205del22 (p.Arg62Alafs) deletion Pathogenic rs1057519483 GRCh37 Chromosome 4, 111542367: 111542388
11 PITX2 NM_153427.2(PITX2): c.191C> T (p.Pro64Leu) single nucleotide variant Pathogenic rs1057519484 GRCh38 Chromosome 4, 110621225: 110621225
12 PITX2 NC_000004.12: g.(?_110618049)_(110622472_?)del deletion Pathogenic GRCh37 Chromosome 4, 111539205: 111543628
13 PITX2 NM_153427.2(PITX2): c.648T> A (p.Cys216Ter) single nucleotide variant Pathogenic rs1057519489 GRCh38 Chromosome 4, 110618293: 110618293
14 PITX2 NM_153427.2(PITX2): c.625_626delTC (p.Ser209Argfs) deletion Pathogenic rs1057519488 GRCh38 Chromosome 4, 110618315: 110618316
15 PITX2 NM_153427.2(PITX2): c.555_576del22 (p.Thr186Serfs) deletion Pathogenic rs1057519487 GRCh37 Chromosome 4, 111539521: 111539542
16 PITX2 GRCh37/hg19 4q25(chr4: 111528916-111888401)x1 copy number loss Pathogenic GRCh37 Chromosome 4, 111426357: 111990971
17 PITX2 NM_153427.2(PITX2): c.202dup (p.Thr68Asnfs) duplication Likely pathogenic GRCh37 Chromosome 4, 111542370: 111542370
18 PITX2 NC_000004.12: g.(?_110618181)_(110621345_?)del deletion Likely pathogenic GRCh37 Chromosome 4, 111539337: 111542501
19 PITX2 NM_153427.2(PITX2): c.253-2A> G single nucleotide variant Likely pathogenic GRCh37 Chromosome 4, 111539846: 111539846

Expression for Axenfeld-Rieger Syndrome, Type 1

Search GEO for disease gene expression data for Axenfeld-Rieger Syndrome, Type 1.

Pathways for Axenfeld-Rieger Syndrome, Type 1

GO Terms for Axenfeld-Rieger Syndrome, Type 1

Biological processes related to Axenfeld-Rieger Syndrome, Type 1 according to GeneCards Suite gene sharing:

(show top 50) (show all 73)
# Name GO ID Score Top Affiliating Genes
1 regulation of gene expression GO:0010468 9.98 BMP4 PAX6 PITX3 SHH
2 heart development GO:0007507 9.96 BMP4 FGF8 PITX2 SHH SHOX2
3 skeletal system development GO:0001501 9.94 BMP4 PITX1 SHOX SHOX2
4 anatomical structure morphogenesis GO:0009653 9.93 FGF8 FOXL2 PITX1 PITX2
5 animal organ morphogenesis GO:0009887 9.91 CRX PAX6 PITX2 PITX3
6 kidney development GO:0001822 9.9 BMP4 FGF8 SHH
7 determination of left/right symmetry GO:0007368 9.88 FGF8 PITX2 SHH
8 lung development GO:0030324 9.88 BMP4 FGF8 PITX2 SHH
9 forebrain development GO:0030900 9.87 BMP4 PAX6 SHH
10 smoothened signaling pathway GO:0007224 9.87 BMP4 PAX6 SHH
11 odontogenesis of dentin-containing tooth GO:0042475 9.85 BMP4 PITX2 SHH
12 embryonic limb morphogenesis GO:0030326 9.85 BMP4 SHH SHOX2
13 positive regulation of cell differentiation GO:0045597 9.83 BMP4 FGF8 SHH
14 cell fate commitment GO:0045165 9.81 BMP4 FGF8 PAX6 SHH
15 metanephros development GO:0001656 9.8 BMP4 FGF8 SHH
16 neuron fate commitment GO:0048663 9.79 BMP4 PAX6 SHH
17 branching involved in blood vessel morphogenesis GO:0001569 9.79 FGF8 PITX2 SHH
18 branching involved in ureteric bud morphogenesis GO:0001658 9.78 BMP4 FGF8 PAX2 SHH
19 dopaminergic neuron differentiation GO:0071542 9.77 FGF8 PITX3 SHH
20 branching morphogenesis of an epithelial tube GO:0048754 9.75 BMP4 SHH
21 positive regulation of mesenchymal cell proliferation GO:0002053 9.75 SHH SHOX2
22 lung morphogenesis GO:0060425 9.75 BMP4 FGF8 SHH
23 telencephalon development GO:0021537 9.74 BMP4 FGF8
24 positive regulation of smoothened signaling pathway GO:0045880 9.74 SHH SHOX2
25 outflow tract septum morphogenesis GO:0003148 9.74 BMP4 FGF8
26 thyroid gland development GO:0030878 9.74 FGF8 SHH
27 female gonad development GO:0008585 9.74 FOXL2 PITX2
28 vasculature development GO:0001944 9.74 BMP4 SHH
29 renal system development GO:0072001 9.74 BMP4 SHH
30 embryonic digestive tract morphogenesis GO:0048557 9.74 PITX2 SHH SHOX2
31 signal transduction involved in regulation of gene expression GO:0023019 9.73 FGF8 PAX6
32 positive regulation of neuroblast proliferation GO:0002052 9.73 PAX6 SHH
33 male genitalia development GO:0030539 9.73 FGF8 SHH
34 negative regulation of neurogenesis GO:0050768 9.73 PAX6 PITX3
35 anatomical structure formation involved in morphogenesis GO:0048646 9.73 BMP4 SHH
36 odontogenesis GO:0042476 9.73 BMP4 FGF8 PITX2 SHH
37 cell fate determination GO:0001709 9.72 PAX2 PAX6
38 epithelial tube branching involved in lung morphogenesis GO:0060441 9.72 BMP4 SHH
39 dorsal/ventral neural tube patterning GO:0021904 9.72 BMP4 SHH
40 epithelial to mesenchymal transition involved in endocardial cushion formation GO:0003198 9.72 BMP4 FGF8
41 camera-type eye development GO:0043010 9.72 BMP4 PAX2 PAX6 PITX2 SHH
42 organ induction GO:0001759 9.71 BMP4 FGF8
43 branching involved in salivary gland morphogenesis GO:0060445 9.71 FGF8 SHH
44 embryonic skeletal joint morphogenesis GO:0060272 9.71 BMP4 SHOX2
45 forebrain morphogenesis GO:0048853 9.71 FGF8 HESX1
46 iris morphogenesis GO:0061072 9.71 PAX6 PITX2
47 embryonic morphogenesis GO:0048598 9.71 BMP4 SHH SHOX2
48 mesonephros development GO:0001823 9.7 BMP4 FGF8 PAX2
49 positive regulation of transcription by RNA polymerase II GO:0045944 9.7 BMP4 CRX FOXL2 PAX2 PAX6 PITX1
50 mesenchymal to epithelial transition involved in metanephros morphogenesis GO:0003337 9.69 BMP4 PAX2

Molecular functions related to Axenfeld-Rieger Syndrome, Type 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 9.9 CRX ESX1 FOXL2 HESX1 PAX2 PAX6
2 DNA binding transcription factor activity GO:0003700 9.87 CRX FOXL2 PAX6 PITX1 PITX2 PITX3
3 transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding GO:0001077 9.73 CRX FOXL2 PAX6 PITX1 PITX2 PITX3
4 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.5 CRX FOXL2 HESX1 PAX6 PITX1 PITX2
5 sequence-specific DNA binding GO:0043565 9.32 CRX ESX1 FOXL2 HESX1 PAX6 PITX1

Sources for Axenfeld-Rieger Syndrome, Type 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
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47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
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70 UMLS via Orphanet
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