FND2
MCID: FRN033
MIFTS: 29

Frontonasal Dysplasia 2 (FND2)

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

Aliases & Classifications for Frontonasal Dysplasia 2

MalaCards integrated aliases for Frontonasal Dysplasia 2:

Name: Frontonasal Dysplasia 2 57 72 29 13 6 70
Craniofrontonasal Dysplasia with Alopecia and Hypogonadism 20 58
Frontonasal Dysplasia with Alopecia and Genital Abnomality 20 58
Frontonasal Dysplasia-Alopecia-Genital Anomalies Syndrome 20 58
Frontonasal Dysplasia Type 2 20 58
Alx4-Related Fndag 20 58
Fnd2 57 72
Frontonasal Dysplasia with Alopecia and Genital Anomaly 20
Dysplasia, Frontonasal, Type 2 39

Characteristics:

Orphanet epidemiological data:

58
frontonasal dysplasia-alopecia-genital anomalies syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity


HPO:

31
frontonasal dysplasia 2:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 58  
Rare eye diseases
Rare bone diseases
Rare skin diseases
Developmental anomalies during embryogenesis


Summaries for Frontonasal Dysplasia 2

UniProtKB/Swiss-Prot : 72 Frontonasal dysplasia 2: The term frontonasal dysplasia describes 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.

MalaCards based summary : Frontonasal Dysplasia 2, also known as craniofrontonasal dysplasia with alopecia and hypogonadism, is related to hypertelorism and parietal foramina. An important gene associated with Frontonasal Dysplasia 2 is ALX4 (ALX Homeobox 4). Affiliated tissues include eye, and related phenotypes are nystagmus and depressed nasal bridge

More information from OMIM: 613451 PS136760

Related Diseases for Frontonasal Dysplasia 2

Diseases in the Frontonasal Dysplasia 1 family:

Frontonasal Dysplasia 2 Frontonasal Dysplasia 3
Six2-Related Frontonasal Dysplasia

Diseases related to Frontonasal Dysplasia 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hypertelorism 10.1
2 parietal foramina 10.1
3 meningocele 10.1
4 alopecia 10.1
5 frontonasal dysplasia 1 10.0
6 meningoencephalocele 10.0

Graphical network of the top 20 diseases related to Frontonasal Dysplasia 2:



Diseases related to Frontonasal Dysplasia 2

Symptoms & Phenotypes for Frontonasal Dysplasia 2

Human phenotypes related to Frontonasal Dysplasia 2:

58 31 (show all 46)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000639
2 depressed nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0005280
3 hypertelorism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000316
4 anteverted nares 58 31 hallmark (90%) Very frequent (99-80%) HP:0000463
5 intellectual disability, mild 58 31 hallmark (90%) Very frequent (99-80%) HP:0001256
6 brachycephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000248
7 strabismus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000486
8 cryptorchidism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000028
9 alopecia 58 31 occasional (7.5%) Very frequent (99-80%) HP:0001596
10 upslanted palpebral fissure 58 31 hallmark (90%) Very frequent (99-80%) HP:0000582
11 intellectual disability, moderate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002342
12 telecanthus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000506
13 underdeveloped nasal alae 58 31 hallmark (90%) Very frequent (99-80%) HP:0000430
14 encephalocele 58 31 hallmark (90%) Very frequent (99-80%) HP:0002084
15 broad philtrum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000289
16 hypogonadism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000135
17 coronal craniosynostosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0004440
18 bifid nose 58 31 hallmark (90%) Very frequent (99-80%) HP:0011803
19 calvarial skull defect 31 hallmark (90%) HP:0001362
20 agenesis of corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0001274
21 frontal bossing 58 31 frequent (33%) Frequent (79-30%) HP:0002007
22 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001511
23 low-set ears 58 31 frequent (33%) Frequent (79-30%) HP:0000369
24 microphthalmia 58 31 frequent (33%) Frequent (79-30%) HP:0000568
25 fine hair 58 31 frequent (33%) Frequent (79-30%) HP:0002213
26 scrotal hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0000046
27 oligohydramnios 58 31 frequent (33%) Frequent (79-30%) HP:0001562
28 conical tooth 58 31 frequent (33%) Frequent (79-30%) HP:0000698
29 agenesis of cerebellar vermis 58 31 frequent (33%) Frequent (79-30%) HP:0002335
30 intellectual disability 31 occasional (7.5%) HP:0001249
31 hypohidrosis 31 occasional (7.5%) HP:0000966
32 decreased lacrimation 31 occasional (7.5%) HP:0000633
33 abnormality of the dentition 58 Frequent (79-30%)
34 wide nasal bridge 31 HP:0000431
35 microcephaly 31 HP:0000252
36 depressed nasal ridge 31 HP:0000457
37 skull defect 58 Very frequent (99-80%)
38 craniosynostosis 31 HP:0001363
39 hypoplasia of the corpus callosum 31 HP:0002079
40 sparse eyelashes 31 HP:0000653
41 broad columella 31 HP:0010761
42 cerebellar vermis hypoplasia 31 HP:0001320
43 short palpebral fissure 31 HP:0012745
44 bifid nasal tip 31 HP:0000456
45 parietal foramina 31 HP:0002697
46 sparse and thin eyebrow 31 HP:0000535

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Nose:
depressed nasal bridge
wide nasal bridge
depressed nasal ridge
bifid nasal tip
wide nasal tip
more
Skeletal Skull:
craniosynostosis
parietal foramina
cranium bifidum

Neurologic Central Nervous System:
hypoplasia of the corpus callosum
cerebellar vermis hypoplasia
intellectual disability (in some patients)
aplasia of the corpus callosum

Skin Nails Hair Skin:
decreased sweating (1 patient)

Head And Neck Eyes:
hypertelorism
short palpebral fissures
upslanting palpebral fissures
decreased lacrimation (1 patient)

Skin Nails Hair Hair:
sparse hair
sparse eyelashes
sparse eyebrows
alopecia (in some patients)

Head And Neck Head:
small head

Clinical features from OMIM®:

613451 (Updated 05-Apr-2021)

Drugs & Therapeutics for Frontonasal Dysplasia 2

Search Clinical Trials , NIH Clinical Center for Frontonasal Dysplasia 2

Genetic Tests for Frontonasal Dysplasia 2

Genetic tests related to Frontonasal Dysplasia 2:

# Genetic test Affiliating Genes
1 Frontonasal Dysplasia 2 29 ALX4

Anatomical Context for Frontonasal Dysplasia 2

MalaCards organs/tissues related to Frontonasal Dysplasia 2:

40
Eye

Publications for Frontonasal Dysplasia 2

Articles related to Frontonasal Dysplasia 2:

# Title Authors PMID Year
1
Skull defects, alopecia, hypertelorism, and notched alae nasi caused by homozygous ALX4 gene mutation. 57 6
24668755 2014
2
Mild nasal malformations and parietal foramina caused by homozygous ALX4 mutations. 57 6
22140057 2012
3
ALX4 dysfunction disrupts craniofacial and epidermal development. 57 6
19692347 2009
4
Skull defects, alopecia and distinctive facies: a new syndrome? 57
18541970 2008
5
A Novel Missense Variant in the ALX4 Gene Underlies Mild to Severe Frontonasal Dysplasia in a Consanguineous Family. 61
32216639 2020
6
Novel homozygous ALX4 mutation causing frontonasal dysplasia-2 in a patient with meningoencephalocele. 61
25963140 2015
7
Potocki-Shaffer deletion encompassing ALX4 in a patient with frontonasal dysplasia phenotype. 61
24376213 2014

Variations for Frontonasal Dysplasia 2

ClinVar genetic disease variations for Frontonasal Dysplasia 2:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ALX4 NM_021926.4(ALX4):c.503del (p.Pro168fs) Deletion Pathogenic 190380 rs876657391 GRCh37: 11:44297172-44297172
GRCh38: 11:44275622-44275622
2 ALX4 NM_021926.4(ALX4):c.291del (p.Gln98fs) Deletion Pathogenic 225543 rs869320717 GRCh37: 11:44331322-44331322
GRCh38: 11:44309772-44309772
3 ALX4 NM_021926.4(ALX4):c.673C>G (p.Gln225Glu) SNV Pathogenic 155903 rs587777701 GRCh37: 11:44297002-44297002
GRCh38: 11:44275452-44275452
4 ALX4 NM_021926.4(ALX4):c.793C>T (p.Arg265Ter) SNV Pathogenic 5020 rs267606653 GRCh37: 11:44289157-44289157
GRCh38: 11:44267607-44267607
5 ALX4 NM_021926.4(ALX4):c.45dup (p.Ala16fs) Duplication Pathogenic 1033575 GRCh37: 11:44331567-44331568
GRCh38: 11:44310017-44310018
6 ALX4 NM_021926.4(ALX4):c.440G>A (p.Ser147Asn) SNV Uncertain significance 735628 rs374726657 GRCh37: 11:44331173-44331173
GRCh38: 11:44309623-44309623
7 ALX4 NM_021926.4(ALX4):c.976G>A (p.Asp326Asn) SNV Uncertain significance 374798 rs186244229 GRCh37: 11:44286664-44286664
GRCh38: 11:44265114-44265114
8 ALX4 NM_021926.4(ALX4):c.1192A>G (p.Met398Val) SNV Uncertain significance 587597 rs1399189995 GRCh37: 11:44286448-44286448
GRCh38: 11:44264898-44264898

Expression for Frontonasal Dysplasia 2

Search GEO for disease gene expression data for Frontonasal Dysplasia 2.

Pathways for Frontonasal Dysplasia 2

GO Terms for Frontonasal Dysplasia 2

Sources for Frontonasal Dysplasia 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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