MCID: ABL002
MIFTS: 55

Ablepharon-Macrostomia Syndrome

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

Aliases & Classifications for Ablepharon-Macrostomia Syndrome

MalaCards integrated aliases for Ablepharon-Macrostomia Syndrome:

Name: Ablepharon-Macrostomia Syndrome 53 71 36 69
Ablepharon Macrostomia Syndrome 12 72 49 55 28 41 14
Ams 53 49 71
Eye Abnormalities 41 69
Congenital Ablepharon, Absent Eyelashes/eyebrows, Macrostomia, Auricular, Nasal, Genital and Other Systemic Anomalies 49
Poikiloderma with Neutropenia, Clericuzio Type 12
Macrostomia 41

Characteristics:

Orphanet epidemiological data:

55
ablepharon macrostomia syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
overlapping features with barber-say syndrome


HPO:

31
ablepharon-macrostomia syndrome:
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Ablepharon-Macrostomia Syndrome

NIH Rare Diseases : 49 Ablepharon macrostomia syndrome is genetic disorder characterized by absent eyelids (ablepharon) and very large mouth (macrostomia). Other common signs and symptoms include abnormal external ears, fusion (syndactyly) of the hands and feet, skin findings (such as dry and coarse skin or redundant folds of skin), absent or sparse hair, genital malformations, and developmental delay. Other reported findings include underdeveloped cheeks (malar hypoplasia), absent or very small (hypoplastic) nipples, umbilical abnormalities and growth retardation. It belongs to a group of diseases called ectodermal dysplasias (genetic disorders that involve defects in the skin, hair, nails, sweat glands, and/or teeth). Ablepharon macrostomia syndrome is caused by mutations in the TWIST2 gene. Inheritance is autosomal dominant, but most cases are sporadic (when there are no other cases in the family). Treatment is aimed toward correcting the problems that are present. Mutations in TWIST2 gene also cause the Barber Say syndrome and Setleis syndrome, other ectodermal dysplasia syndromes which have very similar features.   Last updated: 3/6/2017

MalaCards based summary : Ablepharon-Macrostomia Syndrome, also known as ablepharon macrostomia syndrome, is related to walker-warburg syndrome and barber-say syndrome, and has symptoms including dry skin, hearing impairment and global developmental delay. An important gene associated with Ablepharon-Macrostomia Syndrome is TWIST2 (Twist Family BHLH Transcription Factor 2), and among its related pathways/superpathways are Ectoderm Differentiation and Signaling pathways regulating pluripotency of stem cells. Affiliated tissues include skin, eye and bone, and related phenotypes are growth/size/body region and craniofacial

OMIM : 53 Ablepharon-macrostomia syndrome is a congenital ectodermal dysplasia characterized by absent eyelids, macrostomia, microtia, redundant skin, sparse hair, dysmorphic nose and ears, variable abnormalities of the nipples, genitalia, fingers, and hands, largely normal intellectual and motor development, and poor growth (summary by Marchegiani et al., 2015). (200110)

UniProtKB/Swiss-Prot : 71 Ablepharon-macrostomia syndrome: A congenital ectodermal dysplasia characterized by absent eyelids, macrostomia, microtia, redundant skin, sparse hair, dysmorphic nose and ears, variable abnormalities of the nipples, genitalia, fingers, and hands, largely normal intellectual and motor development, and poor growth.

Disease Ontology : 12 A syndrome characterized by by the association of ablepharon, macrostomia, abnormal external ears, syndactyly of the hands and feet, skin findings (such as dry and coarse skin or redundant folds of skin), absent or sparse hair, genital malformations and developmental delay. Other reported manifestations include malar hypoplasia, absent or hypoplastic nipples, umbilical abnormalities and growth retardation. It is that has material basis in heterozygous mutation in the TWIST2 gene on chromosome 2q37.

Wikipedia : 72 Ablepharon macrostomia syndrome (AMS) is an extremely rare autosomal recessive genetic disorder... more...

Related Diseases for Ablepharon-Macrostomia Syndrome

Diseases related to Ablepharon-Macrostomia Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 217)
# Related Disease Score Top Affiliating Genes
1 walker-warburg syndrome 31.3 FKRP FKTN LARGE1 POMGNT1 POMT1
2 barber-say syndrome 30.5 CYP26C1 LAX1 TWIST2
3 muscular dystrophy 29.1 FKRP FKTN LARGE1 POMGNT1 POMT1
4 poikiloderma with neutropenia 12.0
5 dwarfism, mental retardation, and eye abnormality 12.0
6 apparent mineralocorticoid excess 11.9
7 phace syndrome 11.5
8 acute mountain sickness 11.2
9 walker dyson syndrome 11.2
10 alport syndrome, x-linked 11.1
11 dysplastic nevus syndrome 10.9
12 hemosiderosis 10.9
13 macrostomia, isolated 10.8
14 aniridia 1 10.8
15 frontonasal dysplasia 1 10.8
16 microphthalmia 10.8
17 alport syndrome, autosomal dominant 10.7
18 alport syndrome, autosomal recessive 10.7
19 microcephaly with or without chorioretinopathy, lymphedema, or mental retardation 10.6
20 kaufman oculocerebrofacial syndrome 10.6
21 knobloch syndrome 1 10.6
22 phace association 10.6
23 pierson syndrome 10.6
24 chromosome 16p13.3 deletion syndrome, proximal 10.6
25 congenital disorder of glycosylation, type iik 10.6
26 stickler syndrome 10.6
27 schimmelpenning-feuerstein-mims syndrome 10.4
28 central hypoventilation syndrome, congenital 10.4
29 mucolipidosis iv 10.4
30 lowe oculocerebrorenal syndrome 10.4
31 leber congenital amaurosis 10.4
32 fukuyama type muscular dystrophy 10.4 FKRP FKTN
33 say syndrome 10.3
34 congenital muscular dystrophy with intellectual disability 10.3 FKRP LARGE1 POMT1
35 focal facial dermal dysplasia 10.3 CYP26C1 TWIST2
36 fryns microphthalmia syndrome 10.3 PAX6 SOX2
37 congenital muscular dystrophy with cerebellar involvement 10.3 FKRP POMGNT1 POMT1
38 congenital muscular dystrophy without intellectual disability 10.3 FKRP FKTN POMT1
39 muscular dystrophy-dystroglycanopathy , type c, 4 10.3 FKRP FKTN
40 muscular dystrophy-dystroglycanopathy 10.3 FKRP POMGNT1 POMT1
41 muscular dystrophy, limb-girdle, type 2l 10.3 FKRP FKTN POMT1
42 congenital nervous system abnormality 10.2 FKTN POMGNT1 POMT1
43 muscular dystrophy, congenital, 1b 10.2 FKRP FKTN
44 cutis laxa 10.2
45 renal agenesis, unilateral 10.2 FRAS1 FREM2
46 neutropenia 10.2
47 cryptophthalmos 10.1 FRAS1 FREM2
48 congenital aphakia 10.1 PAX6 SOX2
49 muscular dystrophy-dystroglycanopathy , type b, 5 10.1 FKRP FKTN POMGNT1 POMT1
50 muscular dystrophy, congenital, lmna-related 10.1 FKRP FKTN POMGNT1 POMT1

Graphical network of the top 20 diseases related to Ablepharon-Macrostomia Syndrome:



Diseases related to Ablepharon-Macrostomia Syndrome

Symptoms & Phenotypes for Ablepharon-Macrostomia Syndrome

Symptoms via clinical synopsis from OMIM:

53
Skin Nails Hair Skin:
dry skin
coarse skin
redundant folds

Genitourinary External Genitalia Male:
ambiguous genitalia

Head And Neck Mouth:
macrostomia
short upper lip (in some patients)
bilateral deficiency of lateral lower lip (in some patients)
unfused labial commissures (in some patients)
absent gingiva (in some patients)

Head And Neck Ears:
external ears rudimentary

Chest Breasts:
nipples absent or rudimentary

Skeletal Hands:
syndactyly of fingers, variable (in some patients)
shortening of metacarpals, variable (in some patients)
fifth-finger camptodactyly (in some patients)

Skin Nails Hair Hair:
lanugo absent

Head And Neck Eyes:
hypertelorism
cryptophthalmos
ablepharon (absent eyelids)
microblepharon
eyebrows absent
more
Genitourinary External Genitalia Female:
ambiguous genitalia

Head And Neck Face:
zygomatic arches absent

Head And Neck Nose:
shape abnormal
deficiency of lateral alae nasi (in some patient)

Abdomen External Features:
ventral hernia

Skeletal Feet:
syndactyly of toes, variable (in some patients)
clubfeet (in some patients)

Neurologic Central Nervous System:
language delayed


Clinical features from OMIM:

200110

Human phenotypes related to Ablepharon-Macrostomia Syndrome:

55 31 (show all 47)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dry skin 55 31 frequent (33%) Frequent (79-30%) HP:0000958
2 hearing impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000365
3 global developmental delay 55 31 frequent (33%) Frequent (79-30%) HP:0001263
4 depressed nasal bridge 55 31 occasional (7.5%) Occasional (29-5%) HP:0005280
5 corneal opacity 55 31 frequent (33%) Frequent (79-30%) HP:0007957
6 delayed speech and language development 55 31 hallmark (90%) Very frequent (99-80%) HP:0000750
7 umbilical hernia 55 31 frequent (33%) Frequent (79-30%) HP:0001537
8 microtia 55 31 hallmark (90%) Very frequent (99-80%) HP:0008551
9 anteverted nares 55 31 frequent (33%) Frequent (79-30%) HP:0000463
10 visual impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000505
11 thin skin 55 31 frequent (33%) Frequent (79-30%) HP:0000963
12 corneal erosion 55 31 occasional (7.5%) Occasional (29-5%) HP:0200020
13 microdontia 55 31 frequent (33%) Frequent (79-30%) HP:0000691
14 growth delay 55 31 occasional (7.5%) Occasional (29-5%) HP:0001510
15 aplasia/hypoplasia of the nipples 55 31 frequent (33%) Frequent (79-30%) HP:0006709
16 myopia 55 31 frequent (33%) Frequent (79-30%) HP:0000545
17 underdeveloped nasal alae 55 31 hallmark (90%) Very frequent (99-80%) HP:0000430
18 wide mouth 55 31 hallmark (90%) Very frequent (99-80%) HP:0000154
19 hypoplasia of the maxilla 55 31 frequent (33%) Frequent (79-30%) HP:0000327
20 fine hair 55 31 hallmark (90%) Very frequent (99-80%) HP:0002213
21 hypoplasia of penis 55 31 frequent (33%) Frequent (79-30%) HP:0008736
22 abnormal hair pattern 55 31 occasional (7.5%) Occasional (29-5%) HP:0010720
23 redundant skin 55 31 hallmark (90%) Very frequent (99-80%) HP:0001582
24 thin vermilion border 55 31 occasional (7.5%) Occasional (29-5%) HP:0000233
25 ambiguous genitalia 55 31 frequent (33%) Frequent (79-30%) HP:0000062
26 abnormality of skin pigmentation 55 31 occasional (7.5%) Occasional (29-5%) HP:0001000
27 camptodactyly of finger 55 31 frequent (33%) Frequent (79-30%) HP:0100490
28 toe syndactyly 55 31 occasional (7.5%) Occasional (29-5%) HP:0001770
29 atresia of the external auditory canal 55 31 occasional (7.5%) Occasional (29-5%) HP:0000413
30 sparse hair 55 31 hallmark (90%) Very frequent (99-80%) HP:0008070
31 omphalocele 55 31 occasional (7.5%) Occasional (29-5%) HP:0001539
32 absent eyelashes 55 31 hallmark (90%) Very frequent (99-80%) HP:0000561
33 abnormality of female external genitalia 55 31 frequent (33%) Frequent (79-30%) HP:0000055
34 excessive wrinkled skin 55 31 frequent (33%) Frequent (79-30%) HP:0007392
35 breast hypoplasia 55 31 frequent (33%) Frequent (79-30%) HP:0003187
36 cryptophthalmos 55 31 frequent (33%) Frequent (79-30%) HP:0001126
37 absent eyebrow 55 31 hallmark (90%) Very frequent (99-80%) HP:0002223
38 ablepharon 55 31 hallmark (90%) Very frequent (99-80%) HP:0011224
39 hypertelorism 31 HP:0000316
40 abnormal nasal morphology 31 HP:0005105
41 talipes equinovarus 31 occasional (7.5%) HP:0001762
42 cheekbone underdevelopment 55 Very frequent (99-80%)
43 short metacarpal 31 occasional (7.5%) HP:0010049
44 microtia, third degree 31 HP:0011267
45 short upper lip 31 occasional (7.5%) HP:0000188
46 ventral hernia 31 HP:0002933
47 hypoplasia of the zygomatic bone 31 hallmark (90%) HP:0010669

UMLS symptoms related to Ablepharon-Macrostomia Syndrome:


dry skin, eye manifestations

MGI Mouse Phenotypes related to Ablepharon-Macrostomia Syndrome:

43 (show all 12)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.21 CYP26C1 FKRP FKTN FRAS1 FREM2 LARGE1
2 craniofacial MP:0005382 10.19 FRAS1 FREM2 LARGE1 PAX6 POMGNT1 SMAD4
3 cardiovascular system MP:0005385 10.16 FKRP FRAS1 FREM2 LARGE1 PAX6 POMGNT1
4 mortality/aging MP:0010768 10.13 FKRP FKTN FRAS1 FREM2 LARGE1 OCRL
5 immune system MP:0005387 10.07 CPN1 FKRP FKTN LARGE1 LAX1 PAX6
6 digestive/alimentary MP:0005381 10.02 FRAS1 LARGE1 SMAD4 SOX2 TWIST2 PAX6
7 embryo MP:0005380 10 CYP26C1 FKTN FREM2 PAX6 POMT1 SMAD4
8 muscle MP:0005369 9.96 FKRP FKTN FREM2 LARGE1 PAX6 POMGNT1
9 hearing/vestibular/ear MP:0005377 9.8 FREM2 LARGE1 PAX6 SOX2 TWIST2
10 reproductive system MP:0005389 9.76 TWIST2 FREM2 LARGE1 OCRL PAX6 POMGNT1
11 skeleton MP:0005390 9.56 FKRP FRAS1 FREM2 LARGE1 PAX6 SMAD4
12 vision/eye MP:0005391 9.28 FKRP FRAS1 FREM2 LARGE1 OCRL PAX6

Drugs & Therapeutics for Ablepharon-Macrostomia Syndrome

Search Clinical Trials , NIH Clinical Center for Ablepharon-Macrostomia Syndrome

Inferred drug relations via UMLS 69 / NDF-RT 47 :


Cochrane evidence based reviews: eye abnormalities

Genetic Tests for Ablepharon-Macrostomia Syndrome

Genetic tests related to Ablepharon-Macrostomia Syndrome:

# Genetic test Affiliating Genes
1 Ablepharon Macrostomia Syndrome 28 TWIST2

Anatomical Context for Ablepharon-Macrostomia Syndrome

MalaCards organs/tissues related to Ablepharon-Macrostomia Syndrome:

38
Skin, Eye, Bone, Breast

Publications for Ablepharon-Macrostomia Syndrome

Articles related to Ablepharon-Macrostomia Syndrome:

(show all 18)
# Title Authors Year
1
Barber-Say Syndrome and Ablepharon-Macrostomia Syndrome: A Patient's View. ( 28690482 )
2017
2
Barber-Say syndrome and Ablepharon-Macrostomia syndrome: An overview. ( 27196381 )
2016
3
A Case Report of Ablepharon-Macrostomia Syndrome with Amniotic Membrane Grafting. ( 26600791 )
2015
4
Ablepharon macrostomia syndrome: A distinct genetic entity clinically related to the group of FRAS-FREM complex disorders. ( 24115501 )
2013
5
Ablepharon-Macrostomia syndrome--extension of the phenotype. ( 22002929 )
2011
6
Clinical variant of ablepharon macrostomia syndrome. ( 23198177 )
2011
7
Evidence for autosomal dominant inheritance of ablepharon-macrostomia syndrome. ( 21595001 )
2011
8
Case report supporting that the Barber-Say and ablepharon macrostomia syndromes could represent one disorder. ( 19760652 )
2009
9
Ablepharon-macrostomia syndrome in a 46-year-old woman. ( 15103726 )
2004
10
Ablepharon-macrostomia syndrome. ( 11807864 )
2002
11
Intermediate form of ablepharon-macrostomia syndrome with CNS abnormalities. ( 11746001 )
2001
12
Familial occurrence of ablepharon macrostomia syndrome: eyelid structure and surgical considerations. ( 10721975 )
2000
13
Ablepharon-macrostomia syndrome: first report of familial occurrence. ( 11038439 )
2000
14
Ablepharon macrostomia syndrome with associated cutis laxa: possible localization to 18q. ( 8834257 )
1996
15
Congenital shortening of the anterior lamella of all eyelids: the so-called ablepharon macrostomia syndrome. ( 8746822 )
1995
16
Ablepharon macrostomia syndrome. ( 2036354 )
1991
17
A new feature of the ablepharon macrostomia syndrome: zygomatic arch absence. ( 3293678 )
1988
18
Ablepharon macrostomia syndrome. ( 4003491 )
1985

Variations for Ablepharon-Macrostomia Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Ablepharon-Macrostomia Syndrome:

71
# Symbol AA change Variation ID SNP ID
1 TWIST2 p.Glu75Lys VAR_074675 rs796065049

ClinVar genetic disease variations for Ablepharon-Macrostomia Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 TWIST2 NM_057179.2(TWIST2): c.223G> A (p.Glu75Lys) single nucleotide variant Pathogenic rs796065049 GRCh38 Chromosome 2, 238848438: 238848438

Expression for Ablepharon-Macrostomia Syndrome

Search GEO for disease gene expression data for Ablepharon-Macrostomia Syndrome.

Pathways for Ablepharon-Macrostomia Syndrome

Pathways related to Ablepharon-Macrostomia Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.49 PAX6 SMAD4 SOX2
2 11.27 PAX6 SMAD4 SOX2
3 10.38 FKRP FKTN LARGE1 POMGNT1 POMT1

GO Terms for Ablepharon-Macrostomia Syndrome

Cellular components related to Ablepharon-Macrostomia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.17 CPN1 FKRP FKTN LARGE1 LAX1 OCRL

Biological processes related to Ablepharon-Macrostomia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 anterior/posterior pattern specification GO:0009952 9.5 CYP26C1 PAX6 SMAD4
2 neuron fate commitment GO:0048663 9.43 PAX6 SMAD4
3 pituitary gland development GO:0021983 9.4 PAX6 SOX2
4 morphogenesis of an epithelium GO:0002009 9.37 FRAS1 FREM2
5 protein glycosylation GO:0006486 9.35 FKRP FKTN LARGE1 POMGNT1 POMT1
6 protein O-linked glycosylation GO:0006493 9.33 LARGE1 POMGNT1 POMT1
7 glycoprotein biosynthetic process GO:0009101 9.26 FKRP LARGE1
8 protein O-linked mannosylation GO:0035269 8.92 FKRP FKTN LARGE1 POMT1

Molecular functions related to Ablepharon-Macrostomia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 R-SMAD binding GO:0070412 8.96 PAX6 SMAD4
2 acetylglucosaminyltransferase activity GO:0008375 8.62 LARGE1 POMGNT1

Sources for Ablepharon-Macrostomia Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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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