MCID: CRN248
MIFTS: 46

Craniofrontonasal Dysplasia

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

Aliases & Classifications for Craniofrontonasal Dysplasia

MalaCards integrated aliases for Craniofrontonasal Dysplasia:

Name: Craniofrontonasal Dysplasia 54 12 50 24 56 71 29 13 42 69
Craniofrontonasal Syndrome 12 50 24 56 71 14
Cfnd 50 24 56 71
Cfns 50 24 56 71
Craniofrontonasal Dysostosis 50 24 71

Characteristics:

Orphanet epidemiological data:

56
craniofrontonasal dysplasia
Inheritance: X-linked dominant; Age of onset: Neonatal;

OMIM:

54
Inheritance:
x-linked dominant

Miscellaneous:
primarily diagnosed in females
expression more severe in females than males, except for mosaic males
possible genetic heterogeneity (linkage to xp22 in some families)


HPO:

32
craniofrontonasal dysplasia:
Inheritance x-linked dominant inheritance


Classifications:



Summaries for Craniofrontonasal Dysplasia

NIH Rare Diseases : 50 craniofrontonasal dysplasia is a rare genetic condition caused by a change (mutation) in the efnb1 gene.  main features of this condition include widely spaced eyes (hypertelorism), broad-tipped nose, broad head (brachycephaly), prominent forehead (frontal bossing), asymmetry of facial features, and/or crossed eyes (strabismus). females affected with this condition generally have more symptoms than affected males.  treatment may include surgery to correct the shape of the skull or to adjust the facial features associated with this condition. last updated: 9/23/2015

MalaCards based summary : Craniofrontonasal Dysplasia, also known as craniofrontonasal syndrome, is related to craniofrontonasal syndrome teebi type and hypertelorism, teebi type, and has symptoms including scoliosis, microcephaly and hypertelorism. An important gene associated with Craniofrontonasal Dysplasia is EFNB1 (Ephrin B1), and among its related pathways/superpathways are Axon guidance and Tyrosine Kinases / Adaptors. Affiliated tissues include eye, bone and breast, and related phenotypes are limbs/digits/tail and skeleton

UniProtKB/Swiss-Prot : 71 Craniofrontonasal syndrome: X-linked inherited syndrome characterized by hypertelorism, coronal synostosis with brachycephaly, downslanting palpebral fissures, clefting of the nasal tip, joint anomalies, longitudinally grooved fingernails and other digital anomalies.

OMIM : 54
Craniofrontonasal syndrome is an X-linked developmental disorder that shows paradoxically greater severity in heterozygous females than in hemizygous males. Females have frontonasal dysplasia, craniofacial asymmetry, craniosynostosis, bifid nasal tip, grooved nails, wiry hair, and abnormalities of the thoracic skeleton, whereas males typically show only hypertelorism (Twigg et al., 2004; Wieland et al., 2004). (304110)

Wikipedia : 72 Craniofrontonasal dysplasia (craniofrontonasal syndrome, craniofrontonasal dysostosis, CFND) is a very... more...

Related Diseases for Craniofrontonasal Dysplasia

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

(show all 11)
id Related Disease Score Top Affiliating Genes
1 craniofrontonasal syndrome teebi type 11.8
2 hypertelorism, teebi type 11.6
3 frontonasal dysplasia with alopecia and genital anomaly 10.9
4 webster deming syndrome 10.9
5 frontonasal dysplasia 2 10.9
6 frontonasal dysplasia 1 10.8
7 dysostosis 10.2
8 congenital diaphragmatic hernia 9.9
9 chiari malformation 9.9
10 synostosis 9.9
11 alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis 7.5 ALX1 ALX3 EFNB1 EPHA1 TRIM8 XIST

Graphical network of the top 20 diseases related to Craniofrontonasal Dysplasia:



Diseases related to Craniofrontonasal Dysplasia

Symptoms & Phenotypes for Craniofrontonasal Dysplasia

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
hypotonia
developmental delay
normal intelligence
hypoplasia or agenesis of corpus callosum

Head And Neck- Eyes:
downslanting palpebral fissures
hypertelorism (males and females)
telecanthus (females)
exotropia (females)
nystagmus (females)
more
Skeletal- Limbs:
joint laxity
asymmetric lower limb shortness

Genitourinary- External Genitalia Male:
hypospadias
shawl scrotum

Head And Neck- Neck:
short neck

Skin Nails & Hair- Hair:
widow's peak
low posterior hairline
thick, wiry hair (females and mosaic males)

Skeletal- Feet:
syndactyly
broad halluces

Growth- Height:
short stature (males)

Head And Neck- Teeth:
dental anomalies (mosaic males)

Chest- Ribs Sternum Clavicles And Scapulae:
sprengel deformity (females and mosaic males)
pectus excavatum (males)
clavicle pseudoarthrosis (males)

Skeletal- Skull:
coronal craniosynostosis (females and mosaic males)
increased interorbital distance (males)

Skin Nails & Hair- Skin:
axillary pterygia

Abdomen- External Features:
umbilical hernia

Head And Neck- Nose:
broad nasal root
bifid nasal tip
hypoplastic nasal tip

Head And Neck- Mouth:
cleft palate
cleft lip

Genitourinary- Internal Genitalia Male:
cryptorchidism

Head And Neck- Face:
widow's peak
facial asymmetry
frontal bossing (females and mosaic males)

Skin Nails & Hair- Nails:
grooved nails
brittle nails
longitudinal splitting

Chest- Diaphragm:
diaphragmatic hernia

Head And Neck- Head:
brachycephaly (females and mosaic males)

Chest- External Features:
narrow sloping shoulders

Chest- Breasts:
unilateral breast hypoplasia

Skeletal- Hands:
syndactyly (females and mosaic males)
brachydactyly (males)
fifth finger clinodactyly (females and mosaic males)


Clinical features from OMIM:

304110

Human phenotypes related to Craniofrontonasal Dysplasia:

56 32 (show top 50) (show all 67)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 scoliosis 56 32 frequent (33%) Frequent (79-30%) HP:0002650
2 microcephaly 56 32 frequent (33%) Frequent (79-30%) HP:0000252
3 hypertelorism 56 32 hallmark (90%) Very frequent (99-80%) HP:0000316
4 hypospadias 56 32 occasional (7.5%) Occasional (29-5%) HP:0000047
5 frontal bossing 56 32 hallmark (90%) Very frequent (99-80%) HP:0002007
6 shawl scrotum 56 32 occasional (7.5%) Occasional (29-5%) HP:0000049
7 intellectual disability 56 32 frequent (33%) Frequent (79-30%) HP:0001249
8 hypoplasia of the corpus callosum 56 32 occasional (7.5%) Occasional (29-5%) HP:0002079
9 widow's peak 56 32 frequent (33%) Frequent (79-30%) HP:0000349
10 wide nasal bridge 56 32 hallmark (90%) Very frequent (99-80%) HP:0000431
11 pectus excavatum 56 32 occasional (7.5%) Occasional (29-5%) HP:0000767
12 finger syndactyly 56 32 frequent (33%) Frequent (79-30%) HP:0006101
13 brachycephaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0000248
14 plagiocephaly 56 32 frequent (33%) Frequent (79-30%) HP:0001357
15 downslanted palpebral fissures 56 32 frequent (33%) Frequent (79-30%) HP:0000494
16 low posterior hairline 56 32 frequent (33%) Frequent (79-30%) HP:0002162
17 high palate 56 32 frequent (33%) Frequent (79-30%) HP:0000218
18 joint hyperflexibility 56 32 frequent (33%) Frequent (79-30%) HP:0005692
19 craniosynostosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0001363
20 facial asymmetry 56 32 frequent (33%) Frequent (79-30%) HP:0000324
21 sandal gap 56 32 frequent (33%) Frequent (79-30%) HP:0001852
22 muscular hypotonia 56 32 frequent (33%) Frequent (79-30%) HP:0001252
23 sensorineural hearing impairment 56 32 frequent (33%) Frequent (79-30%) HP:0000407
24 sprengel anomaly 56 32 frequent (33%) Frequent (79-30%) HP:0000912
25 congenital diaphragmatic hernia 56 32 occasional (7.5%) Occasional (29-5%) HP:0000776
26 woolly hair 56 32 frequent (33%) Frequent (79-30%) HP:0002224
27 depressed nasal ridge 56 32 hallmark (90%) Very frequent (99-80%) HP:0000457
28 down-sloping shoulders 56 32 frequent (33%) Frequent (79-30%) HP:0200021
29 oral cleft 56 32 frequent (33%) Frequent (79-30%) HP:0000202
30 broad hallux phalanx 56 32 frequent (33%) Frequent (79-30%) HP:0010059
31 aplasia/hypoplasia of the nipples 56 32 occasional (7.5%) Occasional (29-5%) HP:0006709
32 thickened nuchal skin fold 56 32 frequent (33%) Frequent (79-30%) HP:0000474
33 clinodactyly of the 5th finger 56 32 frequent (33%) Frequent (79-30%) HP:0004209
34 hand polydactyly 56 32 frequent (33%) Frequent (79-30%) HP:0001161
35 camptodactyly of finger 56 32 frequent (33%) Frequent (79-30%) HP:0100490
36 ridged fingernail 56 32 hallmark (90%) Very frequent (99-80%) HP:0008402
37 midline defect of the nose 56 32 hallmark (90%) Very frequent (99-80%) HP:0004122
38 congenital pseudoarthrosis of the clavicle 56 32 frequent (33%) Frequent (79-30%) HP:0006585
39 short stature 32 HP:0004322
40 brachydactyly 32 frequent (33%) HP:0001156
41 nystagmus 32 HP:0000639
42 umbilical hernia 32 HP:0001537
43 joint laxity 32 HP:0001388
44 cleft palate 32 HP:0000175
45 global developmental delay 32 HP:0001263
46 cryptorchidism 32 HP:0000028
47 short neck 32 HP:0000470
48 telecanthus 32 HP:0000506
49 toe syndactyly 32 HP:0001770
50 broad hallux 32 HP:0010055

UMLS symptoms related to Craniofrontonasal Dysplasia:


joint laxity, grooving of nail

MGI Mouse Phenotypes related to Craniofrontonasal Dysplasia:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 limbs/digits/tail MP:0005371 9.26 ALX1 ALX3 EFNB1 EPHA1
2 skeleton MP:0005390 8.92 EFNB1 EPHA1 ALX1 ALX3

Drugs & Therapeutics for Craniofrontonasal Dysplasia

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Genetic Analysis of Craniofrontonasal Syndrome Completed NCT00339846

Search NIH Clinical Center for Craniofrontonasal Dysplasia

Cochrane evidence based reviews: craniofrontonasal dysplasia

Genetic Tests for Craniofrontonasal Dysplasia

Genetic tests related to Craniofrontonasal Dysplasia:

id Genetic test Affiliating Genes
1 Craniofrontonasal Dysplasia 29
2 Craniofrontonasal Syndrome 24 EFNB1

Anatomical Context for Craniofrontonasal Dysplasia

MalaCards organs/tissues related to Craniofrontonasal Dysplasia:

39
Eye, Bone, Breast, Skin

Publications for Craniofrontonasal Dysplasia

Articles related to Craniofrontonasal Dysplasia:

(show all 20)
id Title Authors Year
1
Isolated Sagittal Synostosis in a Boy with Craniofrontonasal Dysplasia and a Novel EFNB1 Mutation. ( 26180728 )
2015
2
Craniofrontonasal dysplasia: variability of the frontonasal suture and implications for treatment. ( 23851793 )
2013
3
Craniofrontonasal dysplasia associated with Chiari malformation. ( 20367343 )
2010
4
Craniofrontonasal dysplasia: a surgical treatment algorithm. ( 18090758 )
2007
5
Visual manifestations of craniofrontonasal dysplasia. ( 17694832 )
2007
6
Further evidence from two families that craniofrontonasal dysplasia maps to Xp22. ( 10450866 )
1999
7
Craniofrontonasal dysplasia. ( 9509720 )
1998
8
Craniofrontonasal dysplasia. ( 9176000 )
1997
9
Craniofrontonasal dysplasia: more severe expression in the mother than in her son. ( 8775424 )
1995
10
Frontonasal and craniofrontonasal dysplasia: preoperative quantitative description of the cranio-orbito-zygomatic region based on computed and conventional tomography. ( 8186226 )
1994
11
Craniofrontonasal dysplasia in two male sibs. ( 8305967 )
1993
12
Craniofrontonasal dysplasia. ( 1468459 )
1992
13
Experience of surgical treatment for craniofrontonasal dysplasia. ( 1746014 )
1991
14
Frontonasal dysplasia or craniofrontonasal dysplasia and the Poland anomaly? ( 2225532 )
1990
15
Craniofrontonasal dysplasia: phenotypic expression in females and males and genetic considerations. ( 3283635 )
1988
16
Craniofrontonasal dysplasia. ( 3346887 )
1988
17
Craniofrontonasal dysplasia. ( 3585934 )
1987
18
New autosomal dominant syndrome resembling craniofrontonasal dysplasia. ( 3425628 )
1987
19
A family with craniofrontonasal dysplasia, and fragile site 12q13 segregating independently. ( 3742859 )
1986
20
Craniofrontonasal dysplasia: clinical and genetic analysis. ( 3742856 )
1986

Variations for Craniofrontonasal Dysplasia

UniProtKB/Swiss-Prot genetic disease variations for Craniofrontonasal Dysplasia:

71 (show all 19)
id Symbol AA change Variation ID SNP ID
1 EFNB1 p.Pro27Arg VAR_023127
2 EFNB1 p.Pro54Leu VAR_023128 rs104894801
3 EFNB1 p.Ile62Thr VAR_023129
4 EFNB1 p.Leu98Ser VAR_023130
5 EFNB1 p.Thr111Ile VAR_023131 rs104894796
6 EFNB1 p.Gln115Pro VAR_023132
7 EFNB1 p.Pro119His VAR_023133
8 EFNB1 p.Pro119Ser VAR_023134
9 EFNB1 p.Pro119Thr VAR_023135
10 EFNB1 p.Thr137Ala VAR_023136
11 EFNB1 p.Ser138Phe VAR_023137
12 EFNB1 p.Gly151Ser VAR_023138 rs28936069
13 EFNB1 p.Gly151Val VAR_023139 rs28936070
14 EFNB1 p.Cys153Ser VAR_023140
15 EFNB1 p.Cys153Tyr VAR_023141
16 EFNB1 p.Thr155Pro VAR_023143
17 EFNB1 p.Met158Ile VAR_023144 rs28935170
18 EFNB1 p.Met158Val VAR_023145 rs28936071
19 EFNB1 p.Ser182Arg VAR_023146

ClinVar genetic disease variations for Craniofrontonasal Dysplasia:

6 (show all 19)
id Gene Variation Type Significance SNP ID Assembly Location
1 EFNB1 EFNB1, EX2-5DEL deletion Pathogenic
2 EFNB1 NM_004429.4(EFNB1): c.332C> T (p.Thr111Ile) single nucleotide variant Pathogenic rs104894796 GRCh37 Chromosome X, 68058663: 68058663
3 EFNB1 NM_004429.4(EFNB1): c.161C> T (p.Pro54Leu) single nucleotide variant Pathogenic/Likely pathogenic rs104894801 GRCh37 Chromosome X, 68058492: 68058492
4 EFNB1 NM_004429.4(EFNB1): c.451G> A (p.Gly151Ser) single nucleotide variant Pathogenic rs28936069 GRCh37 Chromosome X, 68059551: 68059551
5 EFNB1 NM_004429.4(EFNB1): c.452G> T (p.Gly151Val) single nucleotide variant Pathogenic rs28936070 GRCh37 Chromosome X, 68059552: 68059552
6 EFNB1 NM_004429.4(EFNB1): c.472A> G (p.Met158Val) single nucleotide variant Pathogenic rs28936071 GRCh37 Chromosome X, 68059572: 68059572
7 EFNB1 NM_004429.4(EFNB1): c.474G> T (p.Met158Ile) single nucleotide variant Pathogenic rs28935170 GRCh37 Chromosome X, 68059574: 68059574
8 EFNB1 NM_004429.4(EFNB1): c.109T> G (p.Trp37Gly) single nucleotide variant Pathogenic rs104894802 GRCh37 Chromosome X, 68049728: 68049728
9 EFNB1 NM_004429.4(EFNB1): c.110G> A (p.Trp37Ter) single nucleotide variant Pathogenic rs104894803 GRCh37 Chromosome X, 68049729: 68049729
10 EFNB1 NM_004429.4(EFNB1): c.196C> T (p.Arg66Ter) single nucleotide variant Pathogenic rs104894804 GRCh37 Chromosome X, 68058527: 68058527
11 EFNB1 NM_004429.4(EFNB1): c.496C> T (p.Gln166Ter) single nucleotide variant Pathogenic rs587777109 GRCh37 Chromosome X, 68059596: 68059596
12 EFNB1 NC_000023.11 deletion Pathogenic GRCh37 Chromosome X, 68059108: 68067502
13 EFNB1 NM_004429.4(EFNB1): c.407C> T (p.Ser136Leu) single nucleotide variant Likely pathogenic rs1057519033 GRCh37 Chromosome X, 68059507: 68059507
14 EFNB1 NM_004429.4(EFNB1): c.466C> T (p.Arg156Cys) single nucleotide variant Likely pathogenic rs1057519034 GRCh38 Chromosome X, 68839723: 68839723
15 EFNB1 NM_004429.4(EFNB1): c.561delC (p.Asn187Lysfs) deletion Pathogenic rs1057519035 GRCh37 Chromosome X, 68059864: 68059864
16 EFNB1 NM_004429.4(EFNB1): c.128+2T> A single nucleotide variant Pathogenic GRCh37 Chromosome X, 68049749: 68049749
17 EFNB1 NM_004429.4(EFNB1): c.131T> C (p.Phe44Ser) single nucleotide variant Likely pathogenic GRCh37 Chromosome X, 68058462: 68058462
18 EFNB1 NM_004429.4(EFNB1): c.523C> T (p.Gln175Ter) single nucleotide variant Likely pathogenic GRCh38 Chromosome X, 68839983: 68839983
19 EFNB1 NM_004429.4(EFNB1): c.562_563delAC (p.Thr188Cysfs) deletion Pathogenic GRCh37 Chromosome X, 68059865: 68059866

Copy number variations for Craniofrontonasal Dysplasia from CNVD:

7
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 264427 X 65100000 67700000 Copy number EFNB1 Craniofrontonasal syndrome

Expression for Craniofrontonasal Dysplasia

Search GEO for disease gene expression data for Craniofrontonasal Dysplasia.

Pathways for Craniofrontonasal Dysplasia

Pathways related to Craniofrontonasal Dysplasia according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 11.2 EFNB1 EPHA1
2 10.78 EFNB1 EPHA1

GO Terms for Craniofrontonasal Dysplasia

Biological processes related to Craniofrontonasal Dysplasia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 ephrin receptor signaling pathway GO:0048013 9.16 EFNB1 EPHA1
2 embryonic skeletal system morphogenesis GO:0048704 8.96 ALX1 ALX3
3 neural crest cell migration GO:0001755 8.62 ALX1 EFNB1

Sources for Craniofrontonasal Dysplasia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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