MCID: ACR041
MIFTS: 38

Acromelic Frontonasal Dysostosis

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

Aliases & Classifications for Acromelic Frontonasal Dysostosis

MalaCards integrated aliases for Acromelic Frontonasal Dysostosis:

Name: Acromelic Frontonasal Dysostosis 57 12 53 59 75 29 6 15 73
Afnd 57 53 59 75
Acromelic Frontonasal Dysplasia 59 73
Dysostosis, Acromelic Frontonasal 40
Congenital Abnormalities 44
Toriello Syndrome 59
Sweet Syndrome 73

Characteristics:

Orphanet epidemiological data:

59
acromelic frontonasal dysplasia
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: early childhood,infantile;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
brain anomalies variable
four unrelated patients with zswim6 mutations have been described (last curated september 2014)


HPO:

32
acromelic frontonasal dysostosis:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Acromelic Frontonasal Dysostosis

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1827Disease definitionAcromelic frontonasal dysplasia (AFND) is a rare variant of frontonasal dysplasia characterized by distinct craniofacial (large fontanelle, hypertelorism, bifid nasal tip, nasal clefting, brachycephaly, median cleft face, carp-shaped mouth), brain (interhemispheric lipoma, agenesis of the corpus callosum), and limb (tibial hypoplasia/aplasia, club foot, symmetric preaxial polydactyly of the feet and bilateral clubbed and thickened nails of halluces ) malformations as well as intellectual disability. Other manifestations sometimes reported include absent olfactory bulbs, hypopituitarism and cryptorchidism.Visit the Orphanet disease page for more resources.

MalaCards based summary : Acromelic Frontonasal Dysostosis, also known as afnd, is related to kapur-toriello syndrome and sacral hemangiomas multiple congenital abnormalities, and has symptoms including seizures An important gene associated with Acromelic Frontonasal Dysostosis is ZSWIM6 (Zinc Finger SWIM-Type Containing 6). Affiliated tissues include brain, olfactory bulb and eye, and related phenotypes are hypertelorism and thick nasal alae

Disease Ontology : 12 A dysostosis characterized by cranium bifidum, severe hypertelorism, median cleft lip and palate, nasal bifurcation, brachycephaly, large fontanelle, tibial hemimelia, preaxial polydactyly of the feet and brain malformations.

OMIM : 57 Verloes et al. (1992) described a rare variant of frontonasal dysplasia (see FND1, 136760), designated acromelic frontonasal dysplasia (AFND), in which similar craniofacial anomalies are associated with variable central nervous system malformations and limb defects including tibial hypoplasia/aplasia, talipes equinovarus, and preaxial polydactyly of the feet. (603671)

UniProtKB/Swiss-Prot : 75 Acromelic frontonasal dysostosis: A rare variant form of frontonasal dysplasia, an array of abnormalities affecting the eyes, forehead and nose and linked to midfacial dysraphia. The clinical picture is highly variable. Major findings include true ocular hypertelorism, broadening of the nasal root, median facial cleft affecting the nose and/or upper lip and palate, unilateral or bilateral clefting of the alae nasi, lack of formation of the nasal tip, anterior cranium bifidum occultum, a V- shaped or widow's peak frontal hairline. AFND is characterized by the association of frontonasal malformations with various combinations of polydactyly, tibial hypoplasia, epibulbar dermoid, encephalocoele, corpus callosum agenesis and Dandy-Walker malformation.

Related Diseases for Acromelic Frontonasal Dysostosis

Diseases related to Acromelic Frontonasal Dysostosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 52)
# Related Disease Score Top Affiliating Genes
1 kapur-toriello syndrome 12.4
2 sacral hemangiomas multiple congenital abnormalities 11.8
3 neutrophilic dermatosis, acute febrile 11.3
4 frontonasal dysplasia 1 10.9
5 cryptorchidism, unilateral or bilateral 10.6
6 mosaic variegated aneuploidy syndrome 1 10.6
7 syringomyelia 10.6
8 pituitary stalk interruption syndrome 10.6
9 dysostosis 10.5
10 cervical rib 10.4
11 hand-foot-genital syndrome 10.4
12 ureterocele 10.4
13 duodenal atresia 10.4
14 pseudotrisomy 13 syndrome 10.4
15 branchial arch syndrome, x-linked 10.4
16 simpson-golabi-behmel syndrome, type 1 10.4
17 phace association 10.4
18 encephalocraniocutaneous lipomatosis 10.4
19 mosaic variegated aneuploidy syndrome 2 10.4
20 schuurs-hoeijmakers syndrome 10.4
21 retinitis pigmentosa with or without situs inversus 10.4
22 ciliary dyskinesia, primary, 29 10.4
23 thauvin-robinet-faivre syndrome 10.4
24 gabriele-de vries syndrome 10.4
25 mosaic variegated aneuploidy syndrome 3 10.4
26 coronary artery anomaly 10.4
27 hereditary lymphedema 10.4
28 tracheomalacia 10.4
29 laryngeal cleft 10.4
30 limb-body wall complex 10.4
31 phace syndrome 10.4
32 syringobulbia 10.4
33 tracheoesophageal fistula 10.4
34 woolly hair syndrome 10.4
35 polydactyly 9.8
36 pancytopenia 9.6
37 wilms tumor 5 9.5
38 alacrima, achalasia, and mental retardation syndrome 9.5
39 wilms tumor 6 9.5
40 hydranencephaly 9.5
41 aneurysm 9.5
42 neural tube defects 9.3
43 renal hypodysplasia/aplasia 1 9.3
44 galactosialidosis 9.3
45 sudden infant death syndrome 9.3
46 menkes disease 9.3
47 combined immunodeficiency, x-linked 9.3
48 choanal atresia, posterior 9.3
49 respiratory failure 9.3
50 maxillonasal dysplasia, binder type 9.3 ALX3 SHH

Graphical network of the top 20 diseases related to Acromelic Frontonasal Dysostosis:



Diseases related to Acromelic Frontonasal Dysostosis

Symptoms & Phenotypes for Acromelic Frontonasal Dysostosis

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
telecanthus
myopia (in some patients)
glaucoma (rare)
ptosis (in some patients)
more
Head And Neck Head:
brachycephaly
cranium bifidum, anterior

Head And Neck Nose:
broad nasal tip
bifid nose
nostril notching
separation of nostrils

Skeletal Hands:
preaxial polydactyly
preaxial polysyndactyly

Skeletal Limbs:
tibial hypoplasia
patellar hypoplasia or aplasia (in some patients)

Skeletal Skull:
persistent craniopharyngeal canal (rare)
vertical clivus (in some patients)

Skin Nails Hair Nails:
clubbed, thickened nails of halluces (1 patient)

Neurologic Central Nervous System:
agenesis of corpus callosum
seizures
encephalocele
retrocerebellar cyst
mental retardation
more
Head And Neck Mouth:
cleft palate
cleft lip
carp-shaped mouth (in some patients)

Skeletal Feet:
talipes equinovarus
preaxial polydactyly

GenitourinaryInternal GenitaliaMale:
cryptorchidism (in some patients)

Respiratory Airways:
upper airway obstruction, severe (in some patients)

Skin Nails Hair Skin:
vertical creases of plantar surface between first and second toes

Endocrine Features:
hypopituitarism (in some patients)


Clinical features from OMIM:

603671

Human phenotypes related to Acromelic Frontonasal Dysostosis:

59 32 (show all 32)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000316
2 thick nasal alae 59 32 hallmark (90%) Very frequent (99-80%) HP:0009928
3 meningocele 59 32 hallmark (90%) Very frequent (99-80%) HP:0002435
4 broad nasal tip 59 32 hallmark (90%) Very frequent (99-80%) HP:0000455
5 encephalocele 59 32 hallmark (90%) Very frequent (99-80%) HP:0002084
6 bifid nose 59 32 hallmark (90%) Very frequent (99-80%) HP:0011803
7 agenesis of corpus callosum 32 HP:0001274
8 ptosis 32 occasional (7.5%) HP:0000508
9 intellectual disability 32 HP:0001249
10 seizures 32 HP:0001250
11 brachycephaly 32 HP:0000248
12 cleft palate 32 HP:0000175
13 cryptorchidism 32 occasional (7.5%) HP:0000028
14 myopia 32 occasional (7.5%) HP:0000545
15 ventriculomegaly 32 HP:0002119
16 telecanthus 32 HP:0000506
17 glaucoma 32 occasional (7.5%) HP:0000501
18 talipes equinovarus 32 HP:0001762
19 cleft upper lip 32 HP:0000204
20 hypoplasia of the corpus callosum 32 HP:0002079
21 upper airway obstruction 32 occasional (7.5%) HP:0002781
22 u-shaped upper lip vermilion 32 occasional (7.5%) HP:0010806
23 thick nail 32 HP:0001805
24 syndactyly 32 HP:0001159
25 retrocerebellar cyst 32 HP:0006951
26 midline defect of the nose 32 HP:0004122
27 hypopituitarism 32 occasional (7.5%) HP:0040075
28 preaxial polydactyly 32 HP:0100258
29 polydactyly 32 HP:0010442
30 large sella turcica 32 HP:0002690
31 choroid plexus cyst 32 HP:0002190
32 vertical clivus 32 occasional (7.5%) HP:0010559

UMLS symptoms related to Acromelic Frontonasal Dysostosis:


seizures

Drugs & Therapeutics for Acromelic Frontonasal Dysostosis

Search Clinical Trials , NIH Clinical Center for Acromelic Frontonasal Dysostosis

Cochrane evidence based reviews: congenital abnormalities

Genetic Tests for Acromelic Frontonasal Dysostosis

Genetic tests related to Acromelic Frontonasal Dysostosis:

# Genetic test Affiliating Genes
1 Acromelic Frontonasal Dysostosis 29 ZSWIM6

Anatomical Context for Acromelic Frontonasal Dysostosis

MalaCards organs/tissues related to Acromelic Frontonasal Dysostosis:

41
Brain, Olfactory Bulb, Eye, Bone, Pituitary

Publications for Acromelic Frontonasal Dysostosis

Articles related to Acromelic Frontonasal Dysostosis:

# Title Authors Year
1
Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism. ( 26706854 )
2015
2
Exome sequencing identifies a recurrent de novo ZSWIM6 mutation associated with acromelic frontonasal dysostosis. ( 25105228 )
2014
3
Familial acromelic frontonasal dysostosis: autosomal dominant inheritance with reduced penetrance. ( 15264282 )
2004
4
Acromelic frontonasal dysostosis. ( 10190481 )
1999

Variations for Acromelic Frontonasal Dysostosis

UniProtKB/Swiss-Prot genetic disease variations for Acromelic Frontonasal Dysostosis:

75
# Symbol AA change Variation ID SNP ID
1 ZSWIM6 p.Arg1163Trp VAR_071802 rs587777695

ClinVar genetic disease variations for Acromelic Frontonasal Dysostosis:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 ZSWIM6 NM_020928.1(ZSWIM6): c.3487C> T (p.Arg1163Trp) single nucleotide variant Pathogenic rs587777695 GRCh38 Chromosome 5, 61544156: 61544156
2 ZSWIM6 NM_020928.1(ZSWIM6): c.3487C> T (p.Arg1163Trp) single nucleotide variant Pathogenic rs587777695 GRCh37 Chromosome 5, 60839983: 60839983

Copy number variations for Acromelic Frontonasal Dysostosis from CNVD:

7 (show all 27)
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 17329 1 142400000 148000000 Microdeletions and microduplications Congenital abnormalities
2 28404 1 222100000 247249719 Duplication Congenital abnormalities
3 89430 15 18400000 25700000 Duplication Congenital abnormalities
4 107506 17 15900000 22100000 Deletion Congenital abnormalities
5 134872 2 108600000 113800000 Deletion Congenital abnormalities
6 134873 2 108600000 113800000 Deletion Congenital abnormalities
7 155744 20 57900000 62435964 Microdeletion ARFGAP1 Congenital abnormalities
8 155747 20 57900000 62435964 Microdeletion CHRNA4 Congenital abnormalities
9 155750 20 57900000 62435964 Microdeletion KCNQ2 Congenital abnormalities
10 157122 21 13200000 15300000 Duplication Congenital abnormalities
11 227678 7 71800000 77400000 Deletion Congenital abnormalities
12 258158 X 116800000 154913754 Deletion Congenital abnormalities
13 259711 X 140100000 154913754 Duplication Congenital abnormalities
14 262029 X 29400000 31500000 Duplication Congenital abnormalities
15 264071 X 6000000 9500000 Copy number Congenital abnormalities
16 264079 X 6000000 9500000 Deletion Congenital abnormalities
17 264080 X 6000000 9500000 Deletion Congenital abnormalities
18 264081 X 6000000 9500000 Deletion Congenital abnormalities
19 264082 X 6000000 9500000 Deletion Congenital abnormalities
20 264083 X 6000000 9500000 Deletion Congenital abnormalities
21 264084 X 6000000 9500000 Deletion Congenital abnormalities
22 264100 X 6000000 9500000 Duplication Congenital abnormalities
23 264101 X 6000000 9500000 Duplication Congenital abnormalities
24 264102 X 6000000 9500000 Duplication Congenital abnormalities
25 264103 X 6000000 9500000 Duplication Congenital abnormalities
26 264104 X 6000000 9500000 Duplication Congenital abnormalities
27 264105 X 6000000 9500000 Duplication Congenital abnormalities

Expression for Acromelic Frontonasal Dysostosis

Search GEO for disease gene expression data for Acromelic Frontonasal Dysostosis.

Pathways for Acromelic Frontonasal Dysostosis

GO Terms for Acromelic Frontonasal Dysostosis

Biological processes related to Acromelic Frontonasal Dysostosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 pattern specification process GO:0007389 9.16 ALX3 SHH
2 embryonic forelimb morphogenesis GO:0035115 8.96 ALX3 SHH
3 embryonic hindlimb morphogenesis GO:0035116 8.62 ALX3 SHH

Sources for Acromelic Frontonasal 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
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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