GAPOS
MCID: GPS001
MIFTS: 37

Gapo Syndrome (GAPOS)

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

Aliases & Classifications for Gapo Syndrome

MalaCards integrated aliases for Gapo Syndrome:

Name: Gapo Syndrome 57 12 73 20 58 72 29 6 39
Growth Retardation, Alopecia, Pseudoanodontia, and Optic Atrophy 57 72
Growth Retardation, Alopecia, Pseudoanodontia and Optic Atrophy 20 70
Growth Delay-Alopecia-Pseudoanodontia-Optic Atrophy Syndrome 12 58
Gapos 57 72

Characteristics:

Orphanet epidemiological data:

58
gapo syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal; Age of death: adult;

OMIM®:

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

Miscellaneous:
gapo is acronym for growth retardation, alopecia, pseudoanodontia, optic atrophy


HPO:

31
gapo syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare skin diseases
Developmental anomalies during embryogenesis
Rare odontological diseases


Summaries for Gapo Syndrome

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 2067 Definition A multiple congenital anomalies (MCA) syndrome involving connective tissue characterized by Growth retardation, Alopecia, Pseudoanodontia and Ocular manifestations. Epidemiology Approximately 38 patients have been reported in literature since the first description in 1947. Clinical description Patients have a short stature due to post-natal growth retardation and a typical facies with high and bossing forehead, hypertelorism, puffy eyelids, midfacial hypoplasia, depressed nasal bridge, anteverted wide nostrils, thick everted lower lip, micrognathia, low-set ears and premature aging appearance mainly due to redundant hyperelastic skin with unusual wrinkles. Scalp hair may be primarily present but disappears after the first months of life leading to complete or partial alopecia. Eyebrows and/or eyelashes are sparse. Primary and permanent teeth are formed but fail to erupt. Ocular manifestations may include progressive optic atrophy, glaucoma, strabismus, megalocornea, myelinated retinal nerve fiber layer, bilateral keratoconus, nystagmus and ptosis. Otorhinolaryngologic features are choanal atresia, deafness and presence of flaccid and pulsatile masses with an audible murmur in the mastoid area associated with dilated and tortuous scalp veins. Patients have a mild intellectual deficit. Some patients have also been reported with umbilical hernia, hyperextensible joints, osseous anomalies (congenital dislocation of hips or delayed bone age) and cutaneous manifestations (hemangioma or depigmented areas). Other manifestations include intracranial hypertension in infancy, hypothyroidism, mitral valve dysfunction or cardiomyopathy, hepatomegaly, renal impairment and altered gonadal functions (irregular periods or amenorrhea, oligoastenospermia). Etiology Homozygous nonsense or splicing mutations in the ANTXR1 gene, encoding anthrax toxin receptor 1, also known as tumor endothelial marker 8 (TEM8) cause GAPO Syndrome. Diagnostic methods Diagnosis mostly relies on physical examination. Cerebral angiography and magnetic resonance angiography reveal prominent cortical veins, occluded or absent left transverse sinus, left sigmoid sinus, agenesis of left jugular vein, and enlarged veins underlying the palpable scalp masses. Skin biopsy may reveal dermis anomalies including amorphous hyaline substance and recently reported pyoderma vegetans. Antenatal diagnosis Antenatal diagnosis is not possible as features are not detectable by fetal ultrasound. Genetic counseling GAPO syndrome appears to have an autosomal recessive transmission pattern. Management and treatment There is no curative treatment. Management mostly relies on ophthalmologic surveillance and symptomatic treatment of the multiple health problems. Prognosis GAPO patients are reported to have a reduced lifespan (until their 4th -6th decade of life).

MalaCards based summary : Gapo Syndrome, also known as growth retardation, alopecia, pseudoanodontia, and optic atrophy, is related to alopecia and 3-methylglutaconic aciduria, type iii. An important gene associated with Gapo Syndrome is ANTXR1 (ANTXR Cell Adhesion Molecule 1). Affiliated tissues include eye, endothelial and bone, and related phenotypes are frontal bossing and delayed skeletal maturation

Disease Ontology : 12 A syndrome characterized by growth retardation, alopecia, pseudoanodontia and ocular manifestations that has material basis in homozygous or compound heterozygous mutation in ANTXR1 on chromosome 2p13.3.

OMIM® : 57 GAPO syndrome is the acronymic designation for a complex of growth retardation, alopecia, pseudoanodontia (failure of tooth eruption), and progressive optic atrophy (Tipton and Gorlin, 1984). Ilker et al. (1999) and Bayram et al. (2014) noted that optic atrophy is not a consistent feature of the disorder. (230740) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 GAPO syndrome: An autosomal recessive disease characterized by growth retardation, alopecia, failure of tooth eruption, and progressive optic atrophy in some patients.

Wikipedia : 73 GAPO syndrome is a rare, autosomal recessive disorder that causes severe growth retardation, and has... more...

Related Diseases for Gapo Syndrome

Graphical network of the top 20 diseases related to Gapo Syndrome:



Diseases related to Gapo Syndrome

Symptoms & Phenotypes for Gapo Syndrome

Human phenotypes related to Gapo Syndrome:

58 31 (show top 50) (show all 82)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 frontal bossing 58 31 hallmark (90%) Very frequent (99-80%) HP:0002007
2 delayed skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002750
3 depressed nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0005280
4 hypertelorism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000316
5 anteverted nares 58 31 hallmark (90%) Very frequent (99-80%) HP:0000463
6 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
7 thick nasal alae 58 31 hallmark (90%) Very frequent (99-80%) HP:0009928
8 everted lower lip vermilion 58 31 hallmark (90%) Very frequent (99-80%) HP:0000232
9 micrognathia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000347
10 low-set ears 58 31 hallmark (90%) Very frequent (99-80%) HP:0000369
11 alopecia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001596
12 palpebral edema 58 31 hallmark (90%) Very frequent (99-80%) HP:0100540
13 delayed eruption of teeth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000684
14 prematurely aged appearance 58 31 hallmark (90%) Very frequent (99-80%) HP:0007495
15 long philtrum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000343
16 joint hyperflexibility 58 31 hallmark (90%) Very frequent (99-80%) HP:0005692
17 broad forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0000337
18 high forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0000348
19 hyperextensible skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0000974
20 midface retrusion 58 31 hallmark (90%) Very frequent (99-80%) HP:0011800
21 underdeveloped supraorbital ridges 58 31 hallmark (90%) Very frequent (99-80%) HP:0009891
22 sparse eyelashes 58 31 hallmark (90%) Very frequent (99-80%) HP:0000653
23 early balding 58 31 hallmark (90%) Very frequent (99-80%) HP:0002234
24 sparse and thin eyebrow 31 hallmark (90%) HP:0000535
25 mandibular prognathia 58 31 frequent (33%) Frequent (79-30%) HP:0000303
26 umbilical hernia 58 31 frequent (33%) Frequent (79-30%) HP:0001537
27 visual impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000505
28 abnormality of the metaphysis 58 31 frequent (33%) Frequent (79-30%) HP:0000944
29 abnormal form of the vertebral bodies 58 31 frequent (33%) Frequent (79-30%) HP:0003312
30 glaucoma 58 31 frequent (33%) Frequent (79-30%) HP:0000501
31 abnormality of pelvic girdle bone morphology 58 31 frequent (33%) Frequent (79-30%) HP:0002644
32 abnormality of the cerebral vasculature 58 31 frequent (33%) Frequent (79-30%) HP:0100659
33 keratoconus 58 31 frequent (33%) Frequent (79-30%) HP:0000563
34 abnormal palate morphology 58 31 frequent (33%) Frequent (79-30%) HP:0000174
35 skin tags 58 31 frequent (33%) Frequent (79-30%) HP:0010609
36 abnormal clavicle morphology 31 frequent (33%) HP:0000889
37 nystagmus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000639
38 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
39 increased intracranial pressure 58 31 occasional (7.5%) Occasional (29-5%) HP:0002516
40 optic atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000648
41 myopia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000545
42 choanal atresia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000453
43 nephrolithiasis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000787
44 hypopigmented skin patches 58 31 occasional (7.5%) Occasional (29-5%) HP:0001053
45 hemangioma 58 31 occasional (7.5%) Occasional (29-5%) HP:0001028
46 atherosclerosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002621
47 dysmenorrhea 58 31 occasional (7.5%) Occasional (29-5%) HP:0100607
48 decreased skull ossification 58 31 occasional (7.5%) Occasional (29-5%) HP:0004331
49 hypogonadism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000135
50 asymmetry of the thorax 58 31 occasional (7.5%) Occasional (29-5%) HP:0001555

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Face:
frontal bossing
micrognathia
coarsening of facial features with age

Head And Neck Eyes:
nystagmus
hypertelorism
optic atrophy
photophobia
strabismus
more
Head And Neck Nose:
depressed nasal bridge

Head And Neck Mouth:
micrognathia
high arched palate
thick, full lips

Head And Neck Head:
wide anterior fontanel
delayed closure of fontanel

Chest Breasts:
breast hypoplasia
nipple hypoplasia
bell-shaped chest

Growth Other:
growth retardation

Neurologic Central Nervous System:
mental retardation (in some patients)
epilepsy (in some patients)
eeg abnormalities (in some patients)
delayed motor development (in some patients)
enlarged ventricles (in some patients)

Skeletal Limbs:
hyperextensible joints
enlargement of the proximal metaphyses of the humerus
enlargement of the distal metaphyses of the antebrachial bones
enlargement of the long bones, which are shortened
varus arching of the femurs
more
Cardiovascular Heart:
ecg abnormalities

Chest Ribs Sternum Clavicles And Scapulae:
enlargement of the costal arches
enlargement of the proximal third of the clavicle

Skeletal Pelvis:
short square iliac bones

Endocrine Features:
gonadal dysfunction

Skeletal Spine:
scoliosis
increased bone density of the vertebral body end plates

Abdomen Liver:
hepatomegaly

Abdomen External Features:
umbilical hernia

Skin Nails Hair Hair:
alopecia
sparse eyelashes
sparse eyebrows
scalp hair present at birth, lost in early childhood and never regrows
severe hypotrichosis

Skin Nails Hair Nails:
nail dysplasia

Skin Nails Hair Skin:
prominent scalp veins
thick and redundant skin
epidermal inclusion cyst

Skeletal:
delayed bone age

Head And Neck Ears:
protruding ears
folded ears

Head And Neck Teeth:
pseudoanodontia (failure of tooth eruption)

Respiratory Airways:
upper airway infection

Skeletal Skull:
sclerosis of the cranial base
lack of pneumatization of the sphenoidal sinuses
agenesis of the frontal sinuses
sclerosis of the mastoid
thinning of the diploe

Skin Nails Hair Skin Histology:
amorphous hyaline substance

Laboratory Abnormalities:
amorphous hyaline substance (skin biopsy and visceral organs)
widespread interstitial fibrosis (visceral organs)

Clinical features from OMIM®:

230740 (Updated 05-Apr-2021)

Drugs & Therapeutics for Gapo Syndrome

Search Clinical Trials , NIH Clinical Center for Gapo Syndrome

Genetic Tests for Gapo Syndrome

Genetic tests related to Gapo Syndrome:

# Genetic test Affiliating Genes
1 Gapo Syndrome 29 ANTXR1

Anatomical Context for Gapo Syndrome

MalaCards organs/tissues related to Gapo Syndrome:

40
Eye, Endothelial, Bone, Breast

Publications for Gapo Syndrome

Articles related to Gapo Syndrome:

(show top 50) (show all 55)
# Title Authors PMID Year
1
Whole exome sequencing identifies three novel mutations in ANTXR1 in families with GAPO syndrome. 61 57 6
25045128 2014
2
Mutations in ANTXR1 cause GAPO syndrome. 57 6 61
23602711 2013
3
GAPO syndrome: first Egyptian case with ultrastructural changes in the gingiva. 57 6 61
9298746 1997
4
GAPO syndrome (Radiographic clues to early diagnosis). 6 57 61
9180938 1997
5
GAPO syndrome associated with craniofacial vascular malformation. 57 61
20034076 2010
6
GAPO syndrome associated with dilated cardiomyopathy: an unreported association. 61 57
19206158 2009
7
GAPO syndrome: three new Brazilian cases, additional osseous manifestations, and review of the literature. 61 57
18470892 2008
8
GAPO syndrome: a new case of this rare syndrome and a review of the relative importance of different phenotypic features in diagnosis. 57 61
10731088 1999
9
Ophthalmic findings in GAPO syndrome. 61 57
10197743 1999
10
GAPO syndrome: report on the first case in Japan. 61 57
8533828 1995
11
GAPO syndrome: a new case. 61 57
7573163 1995
12
GAPO syndrome in three relatives in a Turkish kindred. 57 61
8135278 1993
13
GAPO syndrome (McKusick 23074)--a connective tissue disorder: report on two affected sibs and on the pathologic findings in the older. 61 57
2248288 1990
14
The GAPO syndrome. 61 57
3565482 1987
15
Growth retardation, alopecia, pseudo-anodontia, and optic atrophy--the GAPO syndrome: report of a patient and review of the literature. 57 61
6507471 1984
16
GAPO syndrome: report of three affected brothers. 61 57
6507472 1984
17
Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis. 61
32244499 2020
18
Changing facial features in a child with GAPO syndrome caused by novel mutation in the ANTXR1 gene and uniparental disomy of chromosome 2. 61
31425299 2019
19
GAPO syndrome with craniosynostosis and intracranial hypertension. 61
31230109 2019
20
Telogen hair loss and androgenetic-like alopecia in GAPO syndrome. 61
30255493 2019
21
GAPO syndrome in seven new patients: Identification of five novel ANTXR1 mutations including the first large intragenic deletion. 61
30575274 2019
22
An LC-MS profiling method reveals a route for apocarotene glycosylation and shows its induction by high light stress in Arabidopsis. 61
30569922 2019
23
Converging physiological roles of the anthrax toxin receptors. 61
31448094 2019
24
GAPO syndrome: a rare genodermatosis presenting with unique features. 61
29377094 2018
25
GAPO Syndrome-A Rare Cause of Osteomyelitis of Jaws; Report of 4 Cases With a Brief Review of the Literature. 61
29304326 2018
26
A novel mutation at ANTXR1 in an Indian patient with growth retardation-alopecia-pseudoanodontia-optic atrophy syndrome. 61
28870703 2017
27
Cell autonomous ANTXR1-mediated regulation of extracellular matrix components in primary fibroblasts. 61
28011198 2017
28
GAPO syndrome: a new syndromic cause of premature ovarian insufficiency. 61
27426988 2016
29
Fell-Muir Lecture: Regulatory mechanisms of skeletal and connective tissue development and homeostasis - lessons from studies of human disorders. 61
27581728 2016
30
New ANTXR1 Gene Mutation for GAPO Syndrome: A Case Report. 61
27587992 2016
31
Regulatory mechanisms of anthrax toxin receptor 1-dependent vascular and connective tissue homeostasis. 61
25572963 2015
32
Arterial and venous thrombosis of the cerebral vasculature in GAPO syndrome. 61
24664815 2014
33
[Tooth eruption disturbances and syndromes]. 61
24881265 2014
34
GAPO syndrome with pansutural craniosynostosis leading to intracranial hypertension. 61
24473423 2014
35
Anesthetic management of a case of GAPO syndrome for craniosynostosis surgery. 61
24250016 2013
36
GAPO syndrome with deafness: new feature or incidental finding? 61
24326960 2013
37
GAPO syndrome associated with vestibular dysfunction and hearing loss. 61
23794220 2013
38
GAPO syndrome: four new patients with congenital glaucoma and myelinated retinal nerve fiber layer. 61
23494824 2013
39
GAPO syndrome associated with pyoderma vegetans: an unreported co-existence. 61
24032282 2013
40
Anesthetic management of a patient with GAPO syndrome for glaucoma surgery. 61
21718384 2011
41
GAPO syndrome: a case associated with bilateral interstitial keratitis and hypothyroidism. 61
20032780 2010
42
GAPO syndrome: a report of two siblings and a review of literature. 61
20537066 2010
43
GAPO syndrome with the novel features of pulmonary hypertension, ankyloglossia, and prognathism. 61
19291762 2009
44
Dental findings in GAPO syndrome: case report. 61
17262136 2006
45
Ophthalmic aspects of GAPO syndrome: case report and review. 61
16272061 2005
46
[Ocular manifestation in GAPO syndrome. Report of the first tunisian case]. 61
14691402 2003
47
GAPO syndrome: first patients with partially empty sella. 61
12099399 2002
48
[Value of imaging in GAPO syndrome]. 61
11965163 2002
49
[GAPO syndrome]. 61
10863181 2000
50
Growth retardation, alopecia, pseudoanodontia, and optic atrophy (GAPO syndrome) with congenital glaucoma. 61
9230846 1997

Variations for Gapo Syndrome

ClinVar genetic disease variations for Gapo Syndrome:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ANTXR1 NM_018153.3(ANTXR1):c.262C>T (p.Arg88Ter) SNV Pathogenic 50907 rs397514701 GRCh37: 2:69271911-69271911
GRCh38: 2:69044779-69044779
2 ANTXR1 NM_032208.2(ANTXR1):c.1435-12A>G SNV Pathogenic 50908 rs879255533 GRCh37: 2:69472345-69472345
GRCh38: 2:69245213-69245213
3 ANTXR1 NM_032208.3(ANTXR1):c.1074del (p.Ala359fs) Deletion Pathogenic 1032944 GRCh37: 2:69397406-69397406
GRCh38: 2:69170274-69170274
4 ANTXR1 NM_018153.3(ANTXR1):c.505C>T (p.Arg169Ter) SNV Likely pathogenic 50906 rs397514700 GRCh37: 2:69302734-69302734
GRCh38: 2:69075602-69075602
5 ANTXR1 NM_032208.2(ANTXR1):c.1221dup (p.Ala408fs) Duplication Likely pathogenic 224851 rs869312895 GRCh37: 2:69409659-69409660
GRCh38: 2:69182527-69182528
6 ANTXR1 NM_032208.2(ANTXR1):c.411A>G (p.Gln137=) SNV Likely pathogenic 224852 rs869312896 GRCh37: 2:69298918-69298918
GRCh38: 2:69071786-69071786
7 ANTXR1 NM_032208.2(ANTXR1):c.1150G>A (p.Gly384Ser) SNV Likely pathogenic 224853 rs869312897 GRCh37: 2:69408978-69408978
GRCh38: 2:69181846-69181846
8 ANTXR1 NM_032208.3(ANTXR1):c.80G>T (p.Gly27Val) SNV Uncertain significance 931360 GRCh37: 2:69240711-69240711
GRCh38: 2:69013579-69013579
9 ANTXR1 NM_032208.3(ANTXR1):c.1105G>A (p.Gly369Ser) SNV Uncertain significance 1032945 GRCh37: 2:69408933-69408933
GRCh38: 2:69181801-69181801

Expression for Gapo Syndrome

Search GEO for disease gene expression data for Gapo Syndrome.

Pathways for Gapo Syndrome

GO Terms for Gapo Syndrome

Sources for Gapo Syndrome

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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