MCID: MLT140
MIFTS: 38

Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Categories: Bone diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Summaries for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 280633 Definition A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by severe global developmental delay, hypotonia, and early-onset seizures, associated with multiple congenital anomalies, such as cardiac (e.g. patent foramen ovale, atrial septal defect, patent ductus arteriosus), genitourinary (i.e. hydrocele, renal collecting system dilatation, hydroureter, hydronephrosis, hypertrophic trabecular urinary bladder) and gastrointestinal (incl. gastroesophageal reflux, anal stenosis, imperforate anus, ano-vestibular fistula) abnormalities, as well as facial dysmorphism which includes coarse facies, a prominent occiput, bitemporal narrowing, epicanthal folds, hypertelorism, nystagmus / strabismus /wandering eyes, low-set, large ears with auricle abnormalities, depressed nasal bridge, upturned nose, long philtrum, large, open mouth with thin lips, high-arched palate, and micro/retrognathia.

MalaCards based summary : Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome, also known as multiple congenital anomalies-hypotonia-seizures syndrome 1, is related to multiple congenital anomalies-hypotonia-seizures syndrome 3 and multiple congenital anomalies-hypotonia-seizures syndrome 1, and has symptoms including seizures, tremor and muscle spasticity. An important gene associated with Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome is PIGN (Phosphatidylinositol Glycan Anchor Biosynthesis Class N), and among its related pathways/superpathways are Glycosylphosphatidylinositol (GPI)-anchor biosynthesis and Metabolism. Affiliated tissues include testis, and related phenotypes are severe global developmental delay and severe muscular hypotonia

Disease Ontology : 12 A lipid metabolism disorder that is characterized by phosphatidylinositol glycan anchor biosynthesis class A (PIGA) deficiency.

KEGG : 36 The Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome (MCAHS) comprises three phenotypes caused by mutations in PIGN, PIGA and PIGT respectively. PIGN and PIGT mutations lead to autosomal recessive disorders whereas PIGA deficiency causes an X-linked lethal disorder. Clinical features are variable dependent on genotypes, often include (neonatal) hypotonia, seizures, various anomalies involving nervous system structural malformations, delayed or lack of psychomotor development, and various congenial organ anomalies.

Related Diseases for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Diseases in the Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome family:

Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2 Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1
Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 3 Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

Diseases related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 35)
# Related Disease Score Top Affiliating Genes
1 multiple congenital anomalies-hypotonia-seizures syndrome 3 32.8 PIGT PGAP2
2 multiple congenital anomalies-hypotonia-seizures syndrome 1 31.8 PIGV PIGT PIGO PIGN PIGL PIGG
3 multiple congenital anomalies-hypotonia-seizures syndrome 2 31.4 PIGV PIGT PIGO PIGL PIGG PIGA
4 hypotonia 30.7 PIGT PIGN PIGG PIGA
5 hemoglobinuria 30.5 PIGT PIGA
6 multiple congenital anomalies-hypotonia-seizures syndrome 4 11.7
7 seizure disorder 10.7
8 alacrima, achalasia, and mental retardation syndrome 10.4
9 encephalopathy 10.4
10 paroxysmal nocturnal hemoglobinuria 10.3
11 anorectal anomalies 10.2
12 gastroesophageal reflux 10.2
13 hypertelorism 10.2
14 pectus excavatum 10.2
15 cryptorchidism, unilateral or bilateral 10.2
16 chorea, childhood-onset, with psychomotor retardation 10.2
17 west syndrome 10.2
18 choreatic disease 10.2
19 hypophosphatasia 10.2
20 epilepsy 10.2
21 hemolytic anemia 10.2
22 cerebral visual impairment 10.2
23 paroxysmal nocturnal hemoglobinuria 1 10.0 PIGT PIGA
24 congenital muscular dystrophy-dystroglycanopathy type a2 10.0 PIGV PIGL
25 bleeding disorder, platelet-type, 9 10.0 PIGT PIGL PIGA
26 hyperphosphatasia with mental retardation syndrome 1 9.8 PIGV PIGO PIGG
27 hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency 9.7 PIGW PIGM
28 glycosylphosphatidylinositol biosynthesis defect 1 9.7 PIGW PIGM
29 agnathia-otocephaly complex 9.7 PIGW PIGN MPPE1
30 coloboma of macula 9.7 PIGV PIGO PIGL PGAP2
31 diaphragmatic hernia, congenital 9.6 PIGW PIGV PIGN PGAP3
32 salt and pepper syndrome 9.6 PIGT PIGM MPPE1
33 hyperphosphatasia-intellectual disability syndrome 8.9 PIGW PIGV PIGO PIGL PIGG PGAP3
34 autosomal recessive non-syndromic intellectual disability 8.9 PIGV PIGO PIGN PIGL PIGG PIGA
35 anterior segment dysgenesis 4 8.1 PIGW PIGV PIGT PIGO PIGN PIGL

Graphical network of the top 20 diseases related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome:



Diseases related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Symptoms & Phenotypes for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Human phenotypes related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome:

31 (show top 50) (show all 82)
# Description HPO Frequency HPO Source Accession
1 severe global developmental delay 31 hallmark (90%) HP:0011344
2 severe muscular hypotonia 31 hallmark (90%) HP:0006829
3 seizure 31 hallmark (90%) HP:0001250
4 tremor 31 frequent (33%) HP:0001337
5 high palate 31 frequent (33%) HP:0000218
6 coarse facial features 31 frequent (33%) HP:0000280
7 gastroesophageal reflux 31 frequent (33%) HP:0002020
8 feeding difficulties in infancy 31 frequent (33%) HP:0008872
9 brachydactyly 31 frequent (33%) HP:0001156
10 hyporeflexia 31 frequent (33%) HP:0001265
11 small hand 31 frequent (33%) HP:0200055
12 tapered finger 31 frequent (33%) HP:0001182
13 short foot 31 frequent (33%) HP:0001773
14 hoarse cry 31 frequent (33%) HP:0001615
15 patent foramen ovale 31 frequent (33%) HP:0001655
16 delayed myelination 31 frequent (33%) HP:0012448
17 macrocephaly at birth 31 frequent (33%) HP:0004488
18 prominent palatine ridges 31 frequent (33%) HP:0010291
19 prominent superior crus of antihelix 31 frequent (33%) HP:0011247
20 hyperreflexia 31 occasional (7.5%) HP:0001347
21 dysphagia 31 occasional (7.5%) HP:0002015
22 short neck 31 occasional (7.5%) HP:0000470
23 gingival overgrowth 31 occasional (7.5%) HP:0000212
24 hypertelorism 31 occasional (7.5%) HP:0000316
25 short nose 31 occasional (7.5%) HP:0003196
26 microtia 31 occasional (7.5%) HP:0008551
27 smooth philtrum 31 occasional (7.5%) HP:0000319
28 anteverted nares 31 occasional (7.5%) HP:0000463
29 full cheeks 31 occasional (7.5%) HP:0000293
30 prominent occiput 31 occasional (7.5%) HP:0000269
31 epicanthus 31 occasional (7.5%) HP:0000286
32 proximal muscle weakness in lower limbs 31 occasional (7.5%) HP:0008994
33 wide mouth 31 occasional (7.5%) HP:0000154
34 narrow mouth 31 occasional (7.5%) HP:0000160
35 upslanted palpebral fissure 31 occasional (7.5%) HP:0000582
36 anal atresia 31 occasional (7.5%) HP:0002023
37 overfolded helix 31 occasional (7.5%) HP:0000396
38 patent ductus arteriosus 31 occasional (7.5%) HP:0001643
39 hydronephrosis 31 occasional (7.5%) HP:0000126
40 thin upper lip vermilion 31 occasional (7.5%) HP:0000219
41 amblyopia 31 occasional (7.5%) HP:0000646
42 ventriculomegaly 31 occasional (7.5%) HP:0002119
43 peripheral pulmonary artery stenosis 31 occasional (7.5%) HP:0004969
44 increased nuchal translucency 31 occasional (7.5%) HP:0010880
45 pes cavus 31 occasional (7.5%) HP:0001761
46 blepharitis 31 occasional (7.5%) HP:0000498
47 narrow chest 31 occasional (7.5%) HP:0000774
48 microretrognathia 31 occasional (7.5%) HP:0000308
49 pulmonary arterial hypertension 31 occasional (7.5%) HP:0002092
50 flexion contracture of toe 31 occasional (7.5%) HP:0005830

UMLS symptoms related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome:


seizures; tremor; muscle spasticity

Drugs & Therapeutics for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Search Clinical Trials , NIH Clinical Center for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Genetic Tests for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Genetic tests related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome:

# Genetic test Affiliating Genes
1 Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 29

Anatomical Context for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

MalaCards organs/tissues related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome:

40
Testis

Publications for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Articles related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome:

(show all 22)
# Title Authors PMID Year
1
Genotype-phenotype correlation of congenital anomalies in multiple congenital anomalies hypotonia seizures syndrome (MCAHS1)/PIGN-related epilepsy. 61 6
26394714 2016
2
Evidence of the milder phenotypic spectrum of c.1582G>A PIGT variant: Delineation based on seven novel Polish patients. 61
32725661 2020
3
The Glycosylphosphatidylinositol biosynthesis pathway in human diseases. 61
32466763 2020
4
Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS). 61
32220244 2020
5
A Novel Mutation in PIGA Associated with Multiple Congenital Anomalies-Hypotonia-Seizure Syndrome 2 (MCAHS2) in a Boy with a Combination of Severe Epilepsy and Gingival Hyperplasia. 61
32256299 2020
6
Case Report: Compound Heterozygous Phosphatidylinositol-Glycan Biosynthesis Class N (PIGN) Mutations in a Chinese Fetus With Hypotonia-Seizures Syndrome 1. 61
33193741 2020
7
The impact of missense mutation in PIGA associated to paroxysmal nocturnal hemoglobinuria and multiple congenital anomalies-hypotonia-seizures syndrome 2: A computational study. 61
31687525 2019
8
PIGT-CDG, a disorder of the glycosylphosphatidylinositol anchor: description of 13 novel patients and expansion of the clinical characteristics. 61
30976099 2019
9
A likely pathogenic variant putatively affecting splicing of PIGA identified in a multiple congenital anomalies hypotonia-seizures syndrome 2 (MCAHS2) family pedigree via whole-exome sequencing. 61
29974678 2018
10
Recessive loss of function PIGN alleles, including an intragenic deletion with founder effect in La Réunion Island, in patients with Fryns syndrome. 61
29330547 2018
11
Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis. 61
29310717 2018
12
Homozygous PIGT Mutation Lead to Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3. 61
29868109 2018
13
[Multiple congenital anomalies-hypotonia-seizures syndrome 1: case report and review of literature]. 61
28273706 2017
14
A homozygous PIGN missense mutation in Soft-Coated Wheaten Terriers with a canine paroxysmal dyskinesia. 61
27891564 2017
15
Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype. 61
27916860 2016
16
A PIGN mutation responsible for multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1) in an Israeli-Arab family. 61
26364997 2016
17
The phenotype of multiple congenital anomalies-hypotonia-seizures syndrome 1: report and review. 61
25920937 2015
18
Expanding the clinical and molecular characteristics of PIGT-CDG, a disorder of glycosylphosphatidylinositol anchors. 61
25943031 2015
19
Paroxysmal nocturnal hemoglobinuria. 61
25237200 2014
20
Novel compound heterozygous PIGT mutations caused multiple congenital anomalies-hypotonia-seizures syndrome 3. 61
24906948 2014
21
Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality. 61
24357517 2014
22
Multiple congenital anomalies-hypotonia-seizures syndrome is caused by a mutation in PIGN. 61
21493957 2011

Variations for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

ClinVar genetic disease variations for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PIGN NM_176787.5(PIGN):c.674+1G>A SNV Likely pathogenic 505688 rs1555694770 GRCh37: 18:59815446-59815446
GRCh38: 18:62148213-62148213
2 PIGN NM_176787.5(PIGN):c.548_549+6del Deletion Likely pathogenic 264637 rs779636222 GRCh37: 18:59821772-59821779
GRCh38: 18:62154539-62154546

Expression for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Search GEO for disease gene expression data for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome.

Pathways for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Pathways related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 Glycosylphosphatidylinositol (GPI)-anchor biosynthesis hsa00563

Pathways related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.51 PIGW PIGV PIGT PIGO PIGN PIGM
2
Show member pathways
13.23 PIGW PIGV PIGT PIGO PIGN PIGM
3
Show member pathways
11.6 PIGW PIGV PIGT PIGO PIGN PIGM
4
Show member pathways
10.89 PIGW PIGV PIGT PIGO PIGN PIGM

GO Terms for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome

Cellular components related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.03 PIGW PIGV PIGT PIGO PIGN PIGM
2 integral component of membrane GO:0016021 9.93 PIGW PIGV PIGT PIGO PIGN PIGM
3 endoplasmic reticulum GO:0005783 9.7 PIGW PIGV PIGT PIGO PIGN PIGM
4 endoplasmic reticulum membrane GO:0005789 9.36 PIGW PIGV PIGT PIGO PIGN PIGM

Biological processes related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 GPI anchor biosynthetic process GO:0006506 9.73 MPPE1 PGAP2 PGAP3 PIGA PIGG PIGL
2 mannosylation GO:0097502 9.26 PIGV PIGM
3 preassembly of GPI anchor in ER membrane GO:0016254 9.17 PIGA PIGG PIGL PIGM PIGN PIGV
4 GPI anchor metabolic process GO:0006505 9.16 PIGW PGAP3

Molecular functions related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.7 PIGW PIGV PIGO PIGN PIGM PIGG
2 transferase activity, transferring glycosyl groups GO:0016757 9.5 PIGV PIGM PIGA
3 mannosyltransferase activity GO:0000030 9.26 PIGV PIGM
4 glycolipid mannosyltransferase activity GO:0004376 8.96 PIGV PIGM
5 mannose-ethanolamine phosphotransferase activity GO:0051377 8.8 PIGO PIGN PIGG

Sources for Multiple Congenital Anomalies-Hypotonia-Seizures 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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