MCID: ACR058
MIFTS: 41

Acrofacial Dysostosis 1, Nager Type

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

Aliases & Classifications for Acrofacial Dysostosis 1, Nager Type

MalaCards integrated aliases for Acrofacial Dysostosis 1, Nager Type:

Name: Acrofacial Dysostosis 1, Nager Type 54 12 50 24 25 71 13
Nager Syndrome 12 50 24 25 56 71 29 69
Nager Acrofacial Dysostosis 12 50 24 25 56 71 14
Preaxial Acrofacial Dysostosis 12 50 25
Afd1 24 25 71
Nager Acrofacial Dysostosis Syndrome 50 25
Nafd 25 56
Mandibulofacial Dysostosis, Treacher Collins Type, with Limb Anomalies 50
Mandibulofacial Dysostosis Treacher Collins Type with Limb Anomalies 71
Mandibulofacial Dysostosis with Preaxial Limb Anomalies 56
Split Hand Deformity-Mandibulofacial Dysostosis 50
Preaxial Mandibulofacial Dysostosis 25
Preaxial Manibulofacial Dysostosis 12
Acrofacial Dysostosis 1 24
Preaxial Acrodysostosis 56
Afd, Nager Type 50
Afd Nager Type 71
Afd 12

Characteristics:

Orphanet epidemiological data:

56
nager syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Age of onset: Antenatal,Neonatal; Age of death: normal life expectancy;

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
variable severity
most cases are sporadic


HPO:

32
acrofacial dysostosis 1, nager type:
Onset and clinical course variable expressivity
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Acrofacial Dysostosis 1, Nager Type

OMIM : 54
Nager syndrome is the prototype for a group of disorders collectively referred to as the acrofacial dysostoses (AFDs), which are characterized by malformation of the craniofacial skeleton and the limbs. The major facial features of Nager syndrome include downslanted palpebral fissures, midface retrusion, and micrognathia, the latter of which often requires the placement of a tracheostomy in early childhood. Limb defects typically involve the anterior (radial) elements of the upper limbs and manifest as small or absent thumbs, triphalangeal thumbs, radial hypoplasia or aplasia, and radioulnar synostosis. Phocomelia of the upper limbs and, occasionally, lower-limb defects have also been reported. The presence of anterior upper-limb defects and the typical lack of lower-limb involvement distinguishes Nager syndrome from Miller syndrome (263750), another rare AFD; however, distinguishing Nager syndrome from other AFDs, including Miller syndrome, can be challenging (summary by Bernier et al., 2012). (154400)

MalaCards based summary : Acrofacial Dysostosis 1, Nager Type, also known as nager syndrome, is related to acrofacial dysostosis, palagonia type and acrofacial dysostosis, and has symptoms including wide mouth, ptosis and micrognathia. An important gene associated with Acrofacial Dysostosis 1, Nager Type is SF3B4 (Splicing Factor 3b Subunit 4), and among its related pathways/superpathways is mRNA Splicing - Minor Pathway. Affiliated tissues include bone, eye and kidney, and related phenotype is Decreased viability in esophageal squamous lineage.

NIH Rare Diseases : 50 nager acrofacial dysostosis is a genetic disorder that affects the limbs and face. the signs and symptoms of nager acrofacial dysostosis vary among affected individuals, even among those in the same family. treatment is tailored to the individual based upon their specific needs. this condition is caused by mutations in the sf3b4 gene. while most cases are sporadic (occurring in families with no prior history of the disorder), autosomal dominant and autosomal recessive inheritance have been reported. last updated: 2/25/2014

UniProtKB/Swiss-Prot : 71 Acrofacial dysostosis 1, Nager type: A form of acrofacial dysostosis, a group of disorders which are characterized by malformation of the craniofacial skeleton and the limbs. The major facial features of AFD1 include downslanted palpebral fissures, midface retrusion, and micrognathia, the latter of which often requires the placement of a tracheostomy in early childhood. Limb defects typically involve the anterior (radial) elements of the upper limbs and manifest as small or absent thumbs, triphalangeal thumbs, radial hyoplasia or aplasia, and radioulnar synostosis. Phocomelia of the upper limbs and, occasionally, lower-limb defects have also been reported.

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

Disease Ontology : 12 An acrofacial dysostosis characterized by underdeveloped cheek bones, very small lower jaw, cleft palate, defects in the middle ear, absent eyelashes, and a notch in the lower eyelids called a coloboma, in children.

Wikipedia : 72 Nager acrofacial dysostosis is a congenital anomaly syndrome.Nager syndrome displays several or all of... more...

Related Diseases for Acrofacial Dysostosis 1, Nager Type

Diseases related to Acrofacial Dysostosis 1, Nager Type via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
id Related Disease Score Top Affiliating Genes
1 acrofacial dysostosis, palagonia type 11.0
2 acrofacial dysostosis 10.8
3 dysostosis 10.8
4 acrofacial dysostosis, catania type 10.8
5 tetralogy of fallot 10.1
6 polydactyly 10.1
7 coloboma 10.1
8 ankylosis 10.1
9 cleft lip 10.1
10 duodenal atresia 9.7 EFTUD2 TXNL4A
11 telogen effluvium 9.7 DHODH EFTUD2 SF3B4
12 chromosomal deletion syndrome 9.1 ARSE DHODH EFTUD2 SF3B4 TXNL4A
13 mental retardation, autosomal recessive 46 8.8 DHODH EFTUD2 SF3B4 TXNL4A VWA1

Graphical network of the top 20 diseases related to Acrofacial Dysostosis 1, Nager Type:



Diseases related to Acrofacial Dysostosis 1, Nager Type

Symptoms & Phenotypes for Acrofacial Dysostosis 1, Nager Type

Symptoms via clinical synopsis from OMIM:

54

Growth- Height:
short stature

Neurologic- Central Nervous System:
speech delay
hydrocephalus
polymicrogyria
normal intelligence
aqueductal stenosis

Head And Neck- Head:
microcephaly

Head And Neck- Face:
micrognathia
retrognathia
midface retrusion

Prenatal Manifestations- Delivery:
premature birth

Head And Neck- Nose:
high nasal bridge

Skeletal- Feet:
toe syndactyly
missing toes
hypoplastic toes
overlapping toes
hallux valgus
more
Cardiovascular- Vascular:
patent ductus arteriosus (in some patients)

Respiratory- Airways:
hypoplasia of the epiglottis

Abdomen- Gastroin testinal:
hirschsprung disease

Genitourinary- Kidneys:
unilateral renal agenesis
duplicated calyx

Skeletal- Limbs:
radioulnar synostosis
limitation of elbow extension
short forearms
radial aplasia
radial hypoplasia

Skin Nails & Hair- Hair:
partial to total absence of eyelashes

Skeletal- Spine:
scoliosis
cervical vertebral abnormalities

Head And Neck- Eyes:
downslanting palpebral fissures
partial-total absence of lower eyelashes
lower lid coloboma

Head And Neck- Ears:
low-set ears
posteriorly rotated ears
conductive deafness
preauricular tags
external auditory canal atresia

Head And Neck- Mouth:
cleft palate
cleft lip
trismus
macrostomia
velopharyngeal insufficiency

Skeletal- Pelvis:
hip dislocation

Skeletal- Hands:
triphalangeal thumbs
clinodactyly
syndactyly
thumb aplasia/hypoplasia

Cardiovascular- Heart:
tetralogy of fallot (in some patients)
ventricular septal defect (in some patients)

Respiratory- Larynx:
laryngeal hypoplasia

Chest- Ribs Sternum Clavicles And Scapulae:
hypoplastic first rib

Genitourinary- Internal Genitalia Female:
bicornuate uterus

Skeletal- Skull:
hypoplastic zygomatic arch
hypoplastic mandible

Skin Nails & Hair- Skin:
urticaria pigmentosa

Abdomen- External Features:
gastroschisis


Clinical features from OMIM:

154400

Human phenotypes related to Acrofacial Dysostosis 1, Nager Type:

56 32 (show top 50) (show all 74)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 wide mouth 56 32 frequent (33%) Frequent (79-30%) HP:0000154
2 ptosis 56 32 frequent (33%) Frequent (79-30%) HP:0000508
3 micrognathia 56 32 hallmark (90%) Very frequent (99-80%) HP:0000347
4 cleft palate 56 32 frequent (33%) Frequent (79-30%) HP:0000175
5 joint stiffness 56 32 frequent (33%) Frequent (79-30%) HP:0001387
6 unilateral renal agenesis 56 32 occasional (7.5%) Occasional (29-5%) HP:0000122
7 respiratory insufficiency 56 32 frequent (33%) Frequent (79-30%) HP:0002093
8 downslanted palpebral fissures 56 32 hallmark (90%) Very frequent (99-80%) HP:0000494
9 low-set, posteriorly rotated ears 56 32 occasional (7.5%) Occasional (29-5%) HP:0000368
10 microtia 56 32 frequent (33%) Frequent (79-30%) HP:0008551
11 skeletal dysplasia 56 32 hallmark (90%) Very frequent (99-80%) HP:0002652
12 triphalangeal thumb 56 32 occasional (7.5%) Occasional (29-5%) HP:0001199
13 phocomelia 56 32 occasional (7.5%) Occasional (29-5%) HP:0009829
14 hearing impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0000365
15 lower eyelid coloboma 56 32 frequent (33%) Frequent (79-30%) HP:0000652
16 delayed speech and language development 56 32 hallmark (90%) Very frequent (99-80%) HP:0000750
17 abnormal nasal morphology 56 32 frequent (33%) Frequent (79-30%) HP:0005105
18 non-midline cleft lip 56 32 occasional (7.5%) Occasional (29-5%) HP:0100335
19 hypoplasia of the maxilla 56 32 hallmark (90%) Very frequent (99-80%) HP:0000327
20 aplasia/hypoplasia of the eyebrow 56 32 frequent (33%) Frequent (79-30%) HP:0100840
21 atresia of the external auditory canal 56 32 frequent (33%) Frequent (79-30%) HP:0000413
22 aplasia/hypoplasia of the thumb 56 32 hallmark (90%) Very frequent (99-80%) HP:0009601
23 abnormality of the lower limb 56 32 occasional (7.5%) Occasional (29-5%) HP:0002814
24 hypoplasia of the radius 56 32 frequent (33%) Frequent (79-30%) HP:0002984
25 sparse lower eyelashes 56 32 frequent (33%) Frequent (79-30%) HP:0007776
26 short stature 32 HP:0004322
27 scoliosis 32 HP:0002650
28 microcephaly 32 HP:0000252
29 hydrocephalus 32 HP:0000238
30 low-set ears 32 HP:0000369
31 patent ductus arteriosus 32 occasional (7.5%) HP:0001643
32 premature birth 32 HP:0001622
33 polymicrogyria 32 HP:0002126
34 retrognathia 32 HP:0000278
35 hip dislocation 32 HP:0002827
36 posteriorly rotated ears 32 HP:0000358
37 talipes equinovarus 32 HP:0001762
38 ventricular septal defect 32 occasional (7.5%) HP:0001629
39 tetralogy of fallot 32 HP:0001636
40 clinodactyly 32 HP:0030084
41 toe syndactyly 32 HP:0001770
42 trismus 32 HP:0000211
43 midface retrusion 32 HP:0011800
44 velopharyngeal insufficiency 32 HP:0000220
45 laryngeal hypoplasia 32 HP:0008749
46 hypoplasia of the epiglottis 32 HP:0005349
47 bicornuate uterus 32 HP:0000813
48 radioulnar synostosis 32 HP:0002974
49 hallux valgus 32 HP:0001822
50 broad hallux 32 HP:0010055

GenomeRNAi Phenotypes related to Acrofacial Dysostosis 1, Nager Type according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability in esophageal squamous lineage GR00235-A 9.1 ARSE DHODH EFTUD2 PRRX2 SF3B4 TXNL4A

Drugs & Therapeutics for Acrofacial Dysostosis 1, Nager Type

Search Clinical Trials , NIH Clinical Center for Acrofacial Dysostosis 1, Nager Type

Genetic Tests for Acrofacial Dysostosis 1, Nager Type

Genetic tests related to Acrofacial Dysostosis 1, Nager Type:

id Genetic test Affiliating Genes
1 Nager Syndrome 29 24 SF3B4

Anatomical Context for Acrofacial Dysostosis 1, Nager Type

MalaCards organs/tissues related to Acrofacial Dysostosis 1, Nager Type:

39
Bone, Eye, Kidney, Heart, Skin, Uterus

Publications for Acrofacial Dysostosis 1, Nager Type

Variations for Acrofacial Dysostosis 1, Nager Type

ClinVar genetic disease variations for Acrofacial Dysostosis 1, Nager Type:

6 (show all 23)
id Gene Variation Type Significance SNP ID Assembly Location
1 SF3B4 NM_005850.4(SF3B4): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs387907185 GRCh37 Chromosome 1, 149899651: 149899651
2 SF3B4 NM_005850.4(SF3B4): c.1147dupC (p.His383Profs) duplication Pathogenic rs387907186 GRCh37 Chromosome 1, 149895562: 149895562
3 SF3B4 NM_005850.4(SF3B4): c.1147delC (p.His383Metfs) deletion Pathogenic rs387907187 GRCh37 Chromosome 1, 149895562: 149895562
4 SF3B4 NM_005850.4(SF3B4): c.913+1G> A single nucleotide variant Pathogenic rs797045125 GRCh37 Chromosome 1, 149897727: 149897727
5 SF3B4 NM_005850.4(SF3B4): c.1006C> T (p.Arg336Ter) single nucleotide variant Pathogenic rs397515324 GRCh37 Chromosome 1, 149895814: 149895814
6 SF3B4 NM_005850.4(SF3B4): c.864delT (p.His288Glnfs) deletion Pathogenic rs797045126 GRCh38 Chromosome 1, 149925885: 149925885
7 SF3B4 NM_005850.4(SF3B4): c.1252_1258delCTTCGAG (p.Leu418Alafs) deletion Pathogenic rs797045121 GRCh37 Chromosome 1, 149895451: 149895457
8 SF3B4 NM_005850.4(SF3B4): c.1232delC (p.Pro411Glnfs) deletion Pathogenic rs797045122 GRCh37 Chromosome 1, 149895477: 149895477
9 SF3B4 NM_005850.4(SF3B4): c.1199delC (p.Pro400Leufs) deletion Pathogenic rs797045123 GRCh37 Chromosome 1, 149895510: 149895510
10 SF3B4 NM_005850.4(SF3B4): c.1148dupA (p.His383Glnfs) duplication Pathogenic rs797045124 GRCh37 Chromosome 1, 149895561: 149895561
11 SF3B4 NM_005850.4(SF3B4): c.1060dupC (p.Arg354Profs) duplication Pathogenic rs782357237 GRCh37 Chromosome 1, 149895760: 149895760
12 SF3B4 NM_005850.4(SF3B4): c.836_837insGGGTATG (p.Thr280Glyfs) insertion Pathogenic rs797045127 GRCh37 Chromosome 1, 149897804: 149897805
13 SF3B4 NM_005850.4(SF3B4): c.827dupC (p.Ser277Ilefs) duplication Pathogenic rs797045128 GRCh37 Chromosome 1, 149897814: 149897814
14 SF3B4 NM_005850.4(SF3B4): c.796dupA (p.Met266Asnfs) duplication Pathogenic rs797045129 GRCh37 Chromosome 1, 149897845: 149897845
15 SF3B4 NM_005850.4(SF3B4): c.769delA (p.Ile257Tyrfs) deletion Pathogenic rs797045130 GRCh37 Chromosome 1, 149897872: 149897872
16 SF3B4 NM_005850.4(SF3B4): c.661_664dupCCCA (p.Asn222Thrfs) duplication Pathogenic rs797045131 GRCh37 Chromosome 1, 149898310: 149898313
17 SF3B4 NM_005850.4(SF3B4): c.625C> T (p.Gln209Ter) single nucleotide variant Pathogenic rs797045132 GRCh37 Chromosome 1, 149898349: 149898349
18 SF3B4 NM_005850.4(SF3B4): c.452C> A (p.Ser151Ter) single nucleotide variant Pathogenic rs797045133 GRCh37 Chromosome 1, 149898522: 149898522
19 SF3B4 NM_005850.4(SF3B4): c.88delT (p.Trp30Glyfs) deletion Pathogenic rs797045134 GRCh37 Chromosome 1, 149899133: 149899133
20 SF3B4 NM_005850.4(SF3B4): c.1230_1249del20 (p.Pro411Thrfs) deletion Pathogenic rs797045954 GRCh38 Chromosome 1, 149923568: 149923587
21 SF3B4 NM_005850.4(SF3B4): c.731_743delCACCCCCAGTGCC (p.Pro244Hisfs) deletion Pathogenic rs797045957 GRCh38 Chromosome 1, 149926006: 149926018
22 SF3B4 NM_005850.4(SF3B4): c.193G> T (p.Glu65Ter) single nucleotide variant Pathogenic rs797045955 GRCh38 Chromosome 1, 149926889: 149926889
23 SF3B4 NM_005850.4(SF3B4): c.45_46delGT (p.Tyr16Argfs) deletion Pathogenic rs797045956 GRCh38 Chromosome 1, 149927283: 149927284

Expression for Acrofacial Dysostosis 1, Nager Type

Search GEO for disease gene expression data for Acrofacial Dysostosis 1, Nager Type.

Pathways for Acrofacial Dysostosis 1, Nager Type

Pathways related to Acrofacial Dysostosis 1, Nager Type according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 10.52 EFTUD2 SF3B4 TXNL4A

GO Terms for Acrofacial Dysostosis 1, Nager Type

Cellular components related to Acrofacial Dysostosis 1, Nager Type according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 U4/U6 x U5 tri-snRNP complex GO:0046540 8.96 EFTUD2 TXNL4A
2 spliceosomal complex GO:0005681 8.8 EFTUD2 SF3B4 TXNL4A

Biological processes related to Acrofacial Dysostosis 1, Nager Type according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 mRNA processing GO:0006397 9.43 EFTUD2 SF3B4 TXNL4A
2 RNA splicing GO:0008380 9.33 EFTUD2 SF3B4 TXNL4A
3 mRNA splicing, via spliceosome GO:0000398 9.13 EFTUD2 SF3B4 TXNL4A
4 RNA splicing, via transesterification reactions GO:0000375 8.62 SF3B4 TXNL4A

Sources for Acrofacial Dysostosis 1, Nager Type

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
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33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
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48 NDF-RT
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55 OMIM via Orphanet
59 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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