MCID: FRN036
MIFTS: 39

Frontonasal Dysplasia 1

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

Aliases & Classifications for Frontonasal Dysplasia 1

MalaCards integrated aliases for Frontonasal Dysplasia 1:

Name: Frontonasal Dysplasia 1 53 49 71 28 13
Frontonasal Dysplasia 53 72 49 24 71 36 69
Frontorhiny 53 49 24 55 71 36
Median Facial Cleft Syndrome 53 49 24
Frontonasal Malformation 53 24 71
Fnd1 53 49 71
Fnd 53 24 71
Fnm 53 24 71
Isolated Median Cleft Face Syndrome 49 55
Alx3-Related Frontonasal Dysplasia 49 55
Frontonasal Dysplasia Sequence 24 69
Frontonasal Dysplasia Type 1 49 55
Median Cleft Syndrome 49 71
Isolated Median Cleft Syndrome 49
Frontonasal Malformation; Fnm 53
Frontonasal Dysplasia; Fnd 53
Median Cleft Face Syndrome 49

Characteristics:

Orphanet epidemiological data:

55
frontorhiny
Inheritance: Autosomal recessive; Age of onset: Neonatal;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
majority of patients have normal intelligence


HPO:

31
frontonasal dysplasia 1:
Inheritance autosomal recessive inheritance sporadic


Classifications:



Summaries for Frontonasal Dysplasia 1

NIH Rare Diseases : 49 Frontonasal dysplasia is a rare disease that results from abnormal development of the head and face before birth. Symptoms often vary, however more common symptoms include wide spaced eyes, a widow's peak, and a broad nose. Less common features include eye abnormalities, missing the connection between the two halves of the brain (agenesis of the corpus callosum), hearing loss, and undescended testicles in males (cryptorchidism). Most people with the dysplasia have normal intelligence. There are three main types of frontonasal dysplasia that are distinguished by their genetic causes and symptoms. Other frontonasal dysplasia syndromes have also been described. Frontonasal dysplasia is very rare, with around 100 cases reported in the literature. Type 1 frontonasal dysplasia is caused by mutations (changes) in the ALX3 gene, type 2 is caused by mutations in the ALX4 gene, and type 3 is caused by mutations in the ALX1 gene. Type 1 and type 3 frontonasal dysplasia are inherited in an autosomal recessive manner, whereas frontonasal dysplasia type 2 is inherited in an autosomal dominant manner. Diagnosis is often first suspected when a baby has features consistent with frontonasal dysplasia. X-rays and genetic testing may be used to confirm the diagnosis. Treatment of the disease may include one or more surgeries to correct certain birth defects, as well as early intervention and special education services, if needed. Last updated: 11/8/2017

MalaCards based summary : Frontonasal Dysplasia 1, also known as frontonasal dysplasia, is related to frontonasal dysplasia 3 and frontonasal dysplasia 2, and has symptoms including hypertelorism, low-set ears and agenesis of corpus callosum. An important gene associated with Frontonasal Dysplasia 1 is ALX3 (ALX Homeobox 3). Affiliated tissues include eye, brain and bone.

OMIM : 53 The term frontonasal dysplasia was coined by Sedano et al. (1970) to describe a constellation of findings limited to the face and head. The disorder is defined as 2 or more of the following: (1) true ocular hypertelorism; (2) broadening of the nasal root; (3) median facial cleft affecting the nose and/or upper lip and palate; (4) unilateral or bilateral clefting of the alae nasi; (5) lack of formation of the nasal tip; (6) anterior cranium bifidum occultum (see 168500); and (7) a V-shaped or widow's peak frontal hairline (Sedano and Gorlin, 1988). Most reported cases are sporadic, but a few familial cases have been reported. Twigg et al. (2009) characterized frontonasal malformation (FNM) as a 'very heterogeneous group of disorders' and summarized clinical features. Also see acromelic frontonasal dysplasia (AFND; 603671), frontofacionasal dysplasia (FFND; 229400), oculoauriculofrontonasal syndrome (OAFNS; 601452), the acrofrontofacionasal dysostosis syndromes (201180, 239710), and craniofrontonasal syndrome (304110). (136760)

UniProtKB/Swiss-Prot : 71 Frontonasal dysplasia 1: 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.

Genetics Home Reference : 24 Frontonasal dysplasia is a condition that results from abnormal development of the head and face before birth. People with frontonasal dysplasia have at least two of the following features: widely spaced eyes (ocular hypertelorism); a broad nose; a slit (cleft) in one or both sides of the nose; no nasal tip; a central cleft involving the nose, upper lip, or roof of the mouth (palate); incomplete formation of the front of the skull with skin covering the head where bone should be (anterior cranium bifidum occultum); or a widow's peak hairline.

Wikipedia : 72 Frontonasal dysplasia (FND) is a congenital malformation of the midface. For the diagnosis of FND, a... more...

Related Diseases for Frontonasal Dysplasia 1

Graphical network of the top 20 diseases related to Frontonasal Dysplasia 1:



Diseases related to Frontonasal Dysplasia 1

Symptoms & Phenotypes for Frontonasal Dysplasia 1

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Eyes:
hypertelorism
ptosis
cataract
microphthalmia
coloboma
more
Skeletal Hands:
clinodactyly
brachydactyly
camptodactyly

Head And Neck Mouth:
median cleft lip
median cleft palate

Head And Neck Face:
widow's peak

Head And Neck Ears:
conductive hearing loss
preauricular tag
low-set ear

Head And Neck Head:
cranium bifidum occultum (defect in midline frontal bone)

Skin Nails Hair Skin:
frontal cutaneous lipoma

Neurologic Central Nervous System:
agenesis of corpus callosum
lipoma of corpus callosum
mental retardation
anterior basal encephalocele

Cardiovascular Heart:
tetralogy of fallot

Skeletal Skull:
hypoplastic frontal sinuses
cranium bifidum occultum
maxillary hypoplasia

Skin Nails Hair Hair:
widow's peak

Head And Neck Nose:
broad nasal root
variable bifid nose
broad notched nasal tip
accessory nasal tag
notched alae nasi

Chest External Features:
pectoral muscle hypoplasia/aplasia (poland syndrome)


Clinical features from OMIM:

136760

Human phenotypes related to Frontonasal Dysplasia 1:

31 (show all 49)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 31 hallmark (90%) HP:0000316
2 low-set ears 31 HP:0000369
3 agenesis of corpus callosum 31 HP:0001274
4 clinodactyly 31 HP:0030084
5 hydrocephalus 31 occasional (7.5%) HP:0000238
6 ptosis 31 HP:0000508
7 intellectual disability 31 occasional (7.5%) HP:0001249
8 cataract 31 HP:0000518
9 wide nasal bridge 31 hallmark (90%) HP:0000431
10 short stature 31 occasional (7.5%) HP:0004322
11 cleft palate 31 occasional (7.5%) HP:0000175
12 epicanthus 31 HP:0000286
13 cryptorchidism 31 occasional (7.5%) HP:0000028
14 webbed neck 31 occasional (7.5%) HP:0000465
15 microphthalmia 31 HP:0000568
16 clinodactyly of the 5th finger 31 occasional (7.5%) HP:0004209
17 hypoplasia of the maxilla 31 HP:0000327
18 low-set, posteriorly rotated ears 31 occasional (7.5%) HP:0000368
19 conductive hearing impairment 31 occasional (7.5%) HP:0000405
20 brachydactyly 31 HP:0001156
21 bilateral single transverse palmar creases 31 occasional (7.5%) HP:0007598
22 broad nasal tip 31 HP:0000455
23 tetralogy of fallot 31 HP:0001636
24 choanal atresia 31 occasional (7.5%) HP:0000453
25 flat occiput 31 occasional (7.5%) HP:0005469
26 craniosynostosis 31 occasional (7.5%) HP:0001363
27 holoprosencephaly 31 occasional (7.5%) HP:0001360
28 preauricular skin tag 31 occasional (7.5%) HP:0000384
29 camptodactyly of finger 31 occasional (7.5%) HP:0100490
30 aplasia/hypoplasia of the corpus callosum 31 occasional (7.5%) HP:0007370
31 postaxial hand polydactyly 31 HP:0001162
32 abnormality of cardiovascular system morphology 31 occasional (7.5%) HP:0030680
33 median cleft lip 31 frequent (33%) HP:0000161
34 short columella 31 HP:0002000
35 hypoplastic frontal sinuses 31 HP:0002738
36 coloboma 31 HP:0000589
37 radial deviation of finger 31 HP:0009466
38 camptodactyly 31 HP:0012385
39 median cleft palate 31 HP:0009099
40 widow's peak 31 hallmark (90%) HP:0000349
41 bifid nasal tip 31 frequent (33%) HP:0000456
42 cranium bifidum occultum 31 HP:0004423
43 lipoma of corpus callosum 31 HP:0006931
44 joint contracture of the hand 31 HP:0009473
45 frontal cutaneous lipoma 31 HP:0007541
46 anterior basal encephalocele 31 HP:0006992
47 widely-spaced maxillary central incisors 31 HP:0001566
48 pectoral muscle hypoplasia/aplasia 31 HP:0005258
49 basal encephalocele 31 occasional (7.5%) HP:0011817

Drugs & Therapeutics for Frontonasal Dysplasia 1

Search Clinical Trials , NIH Clinical Center for Frontonasal Dysplasia 1

Genetic Tests for Frontonasal Dysplasia 1

Genetic tests related to Frontonasal Dysplasia 1:

# Genetic test Affiliating Genes
1 Frontonasal Dysplasia 1 28 ALX3

Anatomical Context for Frontonasal Dysplasia 1

MalaCards organs/tissues related to Frontonasal Dysplasia 1:

38
Eye, Brain, Bone, Skin, Testes

Publications for Frontonasal Dysplasia 1

Articles related to Frontonasal Dysplasia 1:

(show top 50) (show all 71)
# Title Authors Year
1
SIX2 gene haploinsufficiency leads to a recognizable phenotype with ptosis, frontonasal dysplasia, and conductive hearing loss. ( 29315086 )
2018
2
Exome sequencing revealed a novel splice site variant in the ALX1 gene underlying frontonasal dysplasia. ( 27324866 )
2017
3
A new frontonasal dysplasia syndrome associated with deletion of the SIX2 gene. ( 26581443 )
2016
4
Frontonasal dysplasia with severe occipital lobe hypoplasia. ( 24756851 )
2014
5
Potocki-shaffer deletion encompassing ALX4 in a patient with frontonasal dysplasia phenotype. ( 24376213 )
2014
6
Defective neural crest migration revealed by a Zebrafish model of Alx1-related frontonasal dysplasia. ( 23059813 )
2013
7
Prenatal Diagnosis of Frontonasal Dysplasia Associated With Bilateral Periventricular Nodular Heterotopia. ( 24196422 )
2013
8
Bifid nose - a mild degree of frontonasal dysplasia. A case report. ( 23810549 )
2013
9
Prenatal diagnosis of frontonasal dysplasia with anterior encephalocele. ( 24592072 )
2013
10
Neurological picture. Bitemporal hemianopsia in frontonasal dysplasia, callosal agenesis, basal meningocele and eye abnormalities. ( 23475785 )
2013
11
Craniofacial features resembling frontonasal dysplasia with a tubulonodular interhemispheric lipoma in the adult 3H1 tuft mouse. ( 22246904 )
2012
12
Frontonasal dysplasia (Median cleft face syndrome). ( 22346197 )
2012
13
Frontonasal dysplasia, callosal agenesis, basal encephalocele, and eye anomalies syndrome with a partial 21q22.3 deletion. ( 22628242 )
2012
14
Frontonasal dysplasia: clinical evaluation on audiological and brainstem electrophysiological profiles. ( 22030970 )
2011
15
Salvage of calvarial bone graft using acellular dermal matrix in nasal reconstruction and secondary rhinoplasty for frontonasal dysplasia. ( 21772175 )
2011
16
A case report of frontonasal dysplasia. ( 20044145 )
2010
17
Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia. ( 20451171 )
2010
18
Frontorhiny, a distinctive presentation of frontonasal dysplasia caused by recessive mutations in the ALX3 homeobox gene. ( 19409524 )
2009
19
Frontonasal dysplasia: a family presenting autosomal dominant inheritance pattern. ( 19400543 )
2009
20
Frontonasal dysplasia, severe neuropsychological delay, and midline central nervous system anomalies: report of 10 Brazilian male patients. ( 19365836 )
2009
21
Mandibulofacial dysostosis, acral anomalies and frontonasal dysplasia: a new form of acrofacial dysostosis. ( 18388791 )
2008
22
Misexpression of Six2 is associated with heritable frontonasal dysplasia and renal hypoplasia in 3H1 Br mice. ( 18570229 )
2008
23
Prenatal diagnosis of frontonasal dysplasia using 3D ultrasound. ( 18973154 )
2008
24
Subtypes of frontonasal dysplasia are useful in determining clinical prognosis. ( 17955515 )
2007
25
Frontonasal dysplasia. ( 16213944 )
2005
26
Angular analysis of corpus callosum in 18 patients with frontonasal dysplasia. ( 15235716 )
2004
27
The Syndrome of Frontonasal Dysplasia, Callosal Agenesis, Basal Encephalocele, and Eye Anomalies - Phenotypic and Aetiological Considerations. ( 15912188 )
2004
28
Frontonasal dysplasia, neuronal migration error and lymphoedema of limbs. ( 15127764 )
2004
29
Frontonasal dysplasia in 3H1 Br/Br mice. ( 12629672 )
2003
30
Frontonasal dysplasia, Poland anomaly and unilateral hypoplasia of lower limb: report on a male patient. ( 14564209 )
2003
31
Multiple pericallosal lipomas in two siblings with frontonasal dysplasia. ( 11950677 )
2002
32
A mild case of frontonasal dysplasia: the rhinologic perspective. ( 12127227 )
2002
33
Prenatal ultrasound diagnosis of frontonasal dysplasia. ( 12001190 )
2002
34
Frontonasal dysplasia, macroblepharon, eyelid colobomas, ear anomalies, macrostomia, mental retardation and CNS structural anomalies: defining the phenotype. ( 11311001 )
2001
35
Hair follicle nevus occurring in frontonasal dysplasia: an electron microscopic observation. ( 11476112 )
2001
36
Two further cases of Sener syndrome: frontonasal dysplasia and dilated Virchow-Robin spaces. ( 10928859 )
2000
37
The syndrome of frontonasal dysplasia, spastic paraplegia, mental retardation and blindness: a case report with CT scan findings and review of literature. ( 10960697 )
2000
38
Frontonasal dysplasia, macroblepharon, eyelid colobomas, ear anomalies, macrostomia, mental retardation, and CNS structural anomalies: another observation. ( 10649800 )
2000
39
Frontonasal dysplasia, macroblepharon, eyelid colobomas, ear anomalies, macrostomia, mental retardation, and CNS structural anomalies. A new syndrome? ( 10327243 )
1999
40
Frontonasal dysplasia with corpus callosum lipoma. ( 10717702 )
1999
41
A female patient with frontonasal dysplasia sequence and frontonasal encephalocele. ( 10517481 )
1999
42
Optic disc anomalies and frontonasal dysplasia. ( 9602627 )
1998
43
Frontonasal dysplasia with optic disc anomalies and other midline craniofacial defects: a report of six cases. ( 9689987 )
1998
44
Frontonasal dysplasia: analysis of 21 cases and literature review. ( 8727576 )
1996
45
Prenatal diagnosis of frontonasal dysplasia (median cleft syndrome). ( 8667491 )
1996
46
Experience with frontonasal dysplasia of varying severity. ( 8811549 )
1996
47
Ocular manifestations of frontonasal dysplasia. ( 8278482 )
1994
48
Severe acrocallosal syndrome or acromelic frontonasal dysplasia? ( 8080574 )
1994
49
Frontonasal dysplasia, lipoma of the corpus callosum and tetralogy of Fallot. ( 8275566 )
1993
50
Frontonasal dysplasia in two successive generations. ( 8362915 )
1993

Variations for Frontonasal Dysplasia 1

UniProtKB/Swiss-Prot genetic disease variations for Frontonasal Dysplasia 1:

71
# Symbol AA change Variation ID SNP ID
1 ALX3 p.Leu168Val VAR_063226 rs121908167
2 ALX3 p.Arg183Trp VAR_063227 rs121908168
3 ALX3 p.Arg196Trp VAR_063228 rs121908170
4 ALX3 p.Asn203Ser VAR_063229 rs121908166

ClinVar genetic disease variations for Frontonasal Dysplasia 1:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 ALX3 ALX3, IVS2AS, A-T, -2 single nucleotide variant Pathogenic
2 ALX3 NM_006492.2(ALX3): c.608A> G (p.Asn203Ser) single nucleotide variant Pathogenic rs121908166 GRCh37 Chromosome 1, 110604172: 110604172
3 ALX3 NM_006492.2(ALX3): c.502C> G (p.Leu168Val) single nucleotide variant Pathogenic rs121908167 GRCh37 Chromosome 1, 110607301: 110607301
4 ALX3 NM_006492.2(ALX3): c.547C> T (p.Arg183Trp) single nucleotide variant Pathogenic rs121908168 GRCh37 Chromosome 1, 110607256: 110607256
5 ALX3 NM_006492.2(ALX3): c.543T> A (p.Tyr181Ter) single nucleotide variant Pathogenic rs121908169 GRCh37 Chromosome 1, 110607260: 110607260
6 ALX3 NM_006492.2(ALX3): c.578_581delCTGA (p.Thr193Argfs) deletion Pathogenic rs387906319 GRCh37 Chromosome 1, 110607222: 110607225
7 ALX3 NM_006492.2(ALX3): c.586C> T (p.Arg196Trp) single nucleotide variant Pathogenic rs121908170 GRCh37 Chromosome 1, 110607217: 110607217

Expression for Frontonasal Dysplasia 1

Search GEO for disease gene expression data for Frontonasal Dysplasia 1.

Pathways for Frontonasal Dysplasia 1

GO Terms for Frontonasal Dysplasia 1

Sources for Frontonasal Dysplasia 1

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