MCID: ACR058
MIFTS: 46

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 53 12 49 24 71 13
Nager Syndrome 53 12 49 24 55 71 28 69
Nager Acrofacial Dysostosis 53 12 49 24 55 71 14
Preaxial Acrofacial Dysostosis 12 49 24
Afd1 53 24 71
Mandibulofacial Dysostosis, Treacher Collins Type, with Limb Anomalies 53 49
Nager Acrofacial Dysostosis Syndrome 49 24
Afd, Nager Type 53 49
Nafd 24 55
Mandibulofacial Dysostosis Treacher Collins Type with Limb Anomalies 71
Mandibulofacial Dysostosis with Preaxial Limb Anomalies 55
Split Hand Deformity-Mandibulofacial Dysostosis 49
Preaxial Mandibulofacial Dysostosis 24
Preaxial Manibulofacial Dysostosis 12
Acrofacial Dysostosis, Nager Type 72
Preaxial Acrodysostosis 55
Afd Nager Type 71
Afd 12

Characteristics:

Orphanet epidemiological data:

55
nager syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Age of onset: Antenatal,Neonatal; Age of death: normal life expectancy;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
variable severity
most cases are sporadic


HPO:

31
acrofacial dysostosis 1, nager type:
Onset and clinical course variable expressivity
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Acrofacial Dysostosis 1, Nager Type

OMIM : 53 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 dysostosis and acrofacial dysostosis, and has symptoms including joint stiffness, ptosis and respiratory insufficiency. 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.

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.

Genetics Home Reference : 24 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.

NIH Rare Diseases : 49 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.

Wikipedia : 72 Nager acrofacial dysostosis is a genetic congenital anomaly syndrome. Nager syndrome displays several or... 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)
# Related Disease Score Top Affiliating Genes
1 dysostosis 30.9 DHODH EFTUD2 SF3B4
2 acrofacial dysostosis 30.7 ARSE DHODH SF3B4 TXNL4A
3 acrofacial dysostosis, catania type 11.1
4 acrofacial dysostosis, palagonia type 11.1
5 radin blood group antigen 10.2
6 coloboma of macula 10.2
7 tetralogy of fallot 10.2
8 lung agenesis 10.2
9 polydactyly 10.2
10 ankylosis 10.2
11 cleft lip 10.2
12 choanal atresia, posterior 9.8 EFTUD2 TXNL4A
13 treacher collins syndrome 1 9.1 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:

53
Head And Neck Ears:
low-set ears
posteriorly rotated ears
preauricular tags
conductive deafness
external auditory canal atresia

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

Head And Neck Head:
microcephaly

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

Skeletal Pelvis:
hip dislocation

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

Genitourinary Kidneys:
unilateral renal agenesis
duplicated calyx

Abdomen External Features:
gastroschisis

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

Skeletal Skull:
hypoplastic mandible
hypoplastic zygomatic arch

Cardiovascular Vascular:
patent ductus arteriosus (in some patients)

Chest RibsSternum Clavicles And Scapulae:
hypoplastic first rib

Skin Nails Hair Skin:
urticaria pigmentosa

Skeletal Hands:
clinodactyly
syndactyly
triphalangeal thumbs
thumb aplasia/hypoplasia

Skeletal Spine:
scoliosis
cervical vertebral abnormalities

Growth Height:
short stature

Head And Neck Face:
micrognathia
retrognathia
midface retrusion

Skeletal Feet:
hallux valgus
toe syndactyly
broad hallux
overlapping toes
clubfeet
more
Prenatal Manifestations Delivery:
premature birth

Genitourinary Internal Genitalia Female:
bicornuate uterus

Respiratory Larynx:
laryngeal hypoplasia

Head And Neck Nose:
high nasal bridge

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

Respiratory Airways:
hypoplasia of the epiglottis

Abdomen Gastroin testinal:
hirschsprung disease

Skin Nails Hair Hair:
partial to total absence of eyelashes


Clinical features from OMIM:

154400

Human phenotypes related to Acrofacial Dysostosis 1, Nager Type:

55 31 (show top 50) (show all 74)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint stiffness 55 31 frequent (33%) Frequent (79-30%) HP:0001387
2 ptosis 55 31 frequent (33%) Frequent (79-30%) HP:0000508
3 respiratory insufficiency 55 31 frequent (33%) Frequent (79-30%) HP:0002093
4 hearing impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0000365
5 skeletal dysplasia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002652
6 delayed speech and language development 55 31 hallmark (90%) Very frequent (99-80%) HP:0000750
7 microtia 55 31 frequent (33%) Frequent (79-30%) HP:0008551
8 cleft palate 55 31 frequent (33%) Frequent (79-30%) HP:0000175
9 micrognathia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000347
10 abnormal nasal morphology 55 31 frequent (33%) Frequent (79-30%) HP:0005105
11 non-midline cleft lip 55 31 occasional (7.5%) Occasional (29-5%) HP:0100335
12 wide mouth 55 31 frequent (33%) Frequent (79-30%) HP:0000154
13 hypoplasia of the maxilla 55 31 hallmark (90%) Very frequent (99-80%) HP:0000327
14 low-set, posteriorly rotated ears 55 31 occasional (7.5%) Occasional (29-5%) HP:0000368
15 downslanted palpebral fissures 55 31 hallmark (90%) Very frequent (99-80%) HP:0000494
16 aplasia/hypoplasia of the eyebrow 55 31 frequent (33%) Frequent (79-30%) HP:0100840
17 triphalangeal thumb 55 31 occasional (7.5%) Occasional (29-5%) HP:0001199
18 atresia of the external auditory canal 55 31 frequent (33%) Frequent (79-30%) HP:0000413
19 aplasia/hypoplasia of the thumb 55 31 hallmark (90%) Very frequent (99-80%) HP:0009601
20 abnormality of the lower limb 55 31 occasional (7.5%) Occasional (29-5%) HP:0002814
21 unilateral renal agenesis 55 31 occasional (7.5%) Occasional (29-5%) HP:0000122
22 lower eyelid coloboma 55 31 frequent (33%) Frequent (79-30%) HP:0000652
23 hypoplasia of the radius 55 31 frequent (33%) Frequent (79-30%) HP:0002984
24 sparse lower eyelashes 55 31 frequent (33%) Frequent (79-30%) HP:0007776
25 phocomelia 55 31 occasional (7.5%) Occasional (29-5%) HP:0009829
26 malar flattening 31 HP:0000272
27 low-set ears 31 HP:0000369
28 clinodactyly 31 HP:0030084
29 hydrocephalus 31 HP:0000238
30 aqueductal stenosis 31 HP:0002410
31 scoliosis 31 HP:0002650
32 microcephaly 31 HP:0000252
33 short stature 31 HP:0004322
34 malformation of the heart and great vessels 55 Occasional (29-5%)
35 retrognathia 31 HP:0000278
36 patent ductus arteriosus 31 occasional (7.5%) HP:0001643
37 short toe 31 HP:0001831
38 prominent nasal bridge 31 HP:0000426
39 aganglionic megacolon 31 HP:0002251
40 hip dislocation 31 HP:0002827
41 conductive hearing impairment 31 HP:0000405
42 tetralogy of fallot 31 HP:0001636
43 ventricular septal defect 31 occasional (7.5%) HP:0001629
44 talipes equinovarus 31 HP:0001762
45 urticaria 31 HP:0001025
46 hallux valgus 31 HP:0001822
47 radioulnar synostosis 31 HP:0002974
48 cheekbone underdevelopment 55 Very frequent (99-80%)
49 midface retrusion 31 HP:0011800
50 abnormality of the palate 55 Frequent (79-30%)

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

25
# 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:

# Genetic test Affiliating Genes
1 Nager Syndrome 28 SF3B4

Anatomical Context for Acrofacial Dysostosis 1, Nager Type

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

38
Bone, Eye, Kidney, Skin, Heart, Uterus

Publications for Acrofacial Dysostosis 1, Nager Type

Articles related to Acrofacial Dysostosis 1, Nager Type:

(show all 19)
# Title Authors Year
1
Synchronous Bilateral Breast Cancer in a Patient With Nager Syndrome. ( 28139434 )
2017
2
A synonymous splicing mutation in the SF3B4 gene segregates in a family with highly variable Nager syndrome. ( 27966544 )
2017
3
Ankylosis of temporomandibular joints after mandibular distraction osteogenesis in patients with Nager syndrome: Report of two cases and literature review. ( 28688869 )
2017
4
Nager syndrome and Pierre Robin sequence. ( 25808856 )
2015
5
A 22-Week-Old Fetus with Nager Syndrome and Congenital Diaphragmatic Hernia due to a Novel SF3B4 Mutation. ( 25337072 )
2014
6
Nager syndrome: confirmation of SF3B4 haploinsufficiency as the major cause. ( 24003905 )
2014
7
Limbal dermoid in Nager syndrome acrofacial dysostosis: A rare case report. ( 23619484 )
2013
8
Clinical and mutation data in 12 patients with the clinical diagnosis of Nager syndrome. ( 23568615 )
2013
9
Possible autosomal recessive inheritance in an infant with acrofacial dysostosis similar to Nager syndrome. ( 23913624 )
2013
10
Haploinsufficiency of SF3B4, a component of the pre-mRNA spliceosomal complex, causes Nager syndrome. ( 22541558 )
2012
11
Temporomandibular joint replacement for ankylosis correction in Nager syndrome: case report and review of the literature. ( 21723020 )
2012
12
Nager syndrome (preaxial acrofacial dysostosis): a case report. ( 15184856 )
2004
13
Newly recognized autosomal recessive acrofacial dysostosis syndrome resembling Nager syndrome. ( 15266620 )
2004
14
Human PRRX1 and PRRX2 genes: cloning, expression, genomic localization, and exclusion as disease genes for Nager syndrome. ( 11063257 )
2000
15
Cloning, characterization, and chromosomal assignment of the human ortholog of murine Zfp-37, a candidate gene for Nager syndrome. ( 9585434 )
1998
16
Urticaria pigmentosa and Nager syndrome. ( 8176025 )
1994
17
Preaxial acrofacial dysostosis (Nager syndrome) associated with an inherited and apparently balanced X;9 translocation: prenatal and postnatal late replication studies. ( 8357008 )
1993
18
Differential diagnosis of Nager acrofacial dysostosis syndrome: report of four patients with Nager syndrome and discussion of other related syndromes. ( 6837625 )
1983
19
Acrofacial dysostosis (Nager syndrome): synopsis and report of a new case. ( 6881198 )
1983

Variations for Acrofacial Dysostosis 1, Nager Type

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

6 (show all 23)
# 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.1252_1258delCTTCGAG (p.Leu418Alafs) deletion Pathogenic rs797045121 GRCh37 Chromosome 1, 149895451: 149895457
7 SF3B4 NM_005850.4(SF3B4): c.1232delC (p.Pro411Glnfs) deletion Pathogenic rs797045122 GRCh37 Chromosome 1, 149895477: 149895477
8 SF3B4 NM_005850.4(SF3B4): c.1199delC (p.Pro400Leufs) deletion Pathogenic rs797045123 GRCh37 Chromosome 1, 149895510: 149895510
9 SF3B4 NM_005850.4(SF3B4): c.1148dupA (p.His383Glnfs) duplication Pathogenic rs797045124 GRCh37 Chromosome 1, 149895561: 149895561
10 SF3B4 NM_005850.4(SF3B4): c.1060dupC (p.Arg354Profs) duplication Pathogenic rs782357237 GRCh37 Chromosome 1, 149895760: 149895760
11 SF3B4 NM_005850.4(SF3B4): c.864delT (p.His288Glnfs) deletion Pathogenic rs797045126 GRCh37 Chromosome 1, 149897777: 149897777
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:

# 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:

# 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:

# 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
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10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
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29 HGMD
30 HMDB
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32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
36 KEGG
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41 MeSH
42 MESH via Orphanet
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58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
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67 TGDB
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70 UMLS via Orphanet
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