MCID: MLT128
MIFTS: 40

Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

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

Aliases & Classifications for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

MalaCards integrated aliases for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2:

Name: Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2 57 12 75 29 13 6 15 73
Mcahs2 57 53 75
Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome Type 2 53 59
Glycosylphosphatidylinositol Biosynthesis Defect 4 57 75
Epileptic Encephalopathy, Early Infantile, 20 57 75
Mcahs Type 2 53 59
Eiee20 57 75
Gpibd4 57 75
Multiple Congenital Anomalies, Hypotonia, Seizures Syndrome, Type 2 ) 40
Glycosylphosphatidylinositol Biosynthesis Defect 4; Gpibd4 57
Epileptic Encephalopathy, Early Infantile, 20; Eiee20 57
Early Infantile Epileptic Encephalopathy 20 53
Ferro-Cerebro-Cutaneous Syndrome 75
Fccs 75

Characteristics:

Orphanet epidemiological data:

59
multiple congenital anomalies-hypotonia-seizures syndrome type 2
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

57
Miscellaneous:
variable severity
onset in utero or early infancy
evidence of systemic iron overload seen in 1 family
may be lethal in infancy
variable extraneurologic features

Inheritance:
x-linked recessive


HPO:

32
multiple congenital anomalies-hypotonia-seizures syndrome 2:
Mortality/Aging death in infancy
Onset and clinical course variable expressivity
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

NIH Rare Diseases : 53 Multiple congenital anomalies-hypotonia-seizuressyndrome type 2 (MCAHS2) is a genetic neurodevelopmental disorder characterized by distinctive facial features, low muscle tone (hypotonia) at birth, myoclonic seizures (which cause jerks or twitches of the upper body, arms, or legs), and various other problems involving the central nervous system, heart, and urinary system. Specific symptoms (especially those not involving the nervous system) and severity vary from person to person, but most children develop severe developmental delay and intellectual disability. This condition is caused by mutations in the PIGA gene on the X chromosome and inheritance is X-linked recessive, so it typically affects boys. However, in some cases, MCAHS2 is not inherited from a parent and is the result of a new mutation occurring for the first time in a person with MCAHS2 (a de novo mutation). Treatment depends on the symptoms present and aims to control symptoms and increase quality of life. The long-term outlook and life expectancy varies depending on severity. Some children with MCAHS2 do not survive beyond infancy.

MalaCards based summary : Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2, also known as mcahs2, is related to ferro-cerebro-cutaneous syndrome and hemosiderosis, and has symptoms including myoclonic seizures An important gene associated with Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2 is PIGA (Phosphatidylinositol Glycan Anchor Biosynthesis Class A), and among its related pathways/superpathways are Creation of C4 and C2 activators and Complement and coagulation cascades. Affiliated tissues include heart, pons and brain, and related phenotypes are macrocephaly and malar flattening

OMIM : 57 Multiple congenital anomalies-hypotonia-seizures syndrome-2 is an X-linked recessive neurodevelopmental disorder characterized by dysmorphic features, neonatal hypotonia, myoclonic seizures, and variable congenital anomalies involving the central nervous, cardiac, and urinary systems. Some affected individuals die in infancy (summary by Johnston et al., 2012). The phenotype shows clinical variability with regard to severity and extraneurologic features. However, most patients present in infancy with early-onset epileptic encephalopathy associated with developmental arrest and subsequent severe neurologic disability (summary by Belet et al., 2014, Kato et al., 2014). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of MCAHS, see MCAHS1 (614080); for a discussion of genetic heterogeneity of EIEE, see 308350; and for a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293). (300868)

UniProtKB/Swiss-Prot : 75 Multiple congenital anomalies-hypotonia-seizures syndrome 2: An X-linked recessive developmental disorder characterized by dysmorphic features, neonatal hypotonia, myoclonic seizures, and variable congenital anomalies involving the central nervous, cardiac, and urinary systems. Most affected individuals die in infancy.

Related Diseases for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

Graphical network of the top 20 diseases related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2:



Diseases related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

Symptoms & Phenotypes for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Face:
malar flattening
micrognathia
coarse facies

Neurologic Peripheral Nervous System:
hyperreflexia

Head And Neck Teeth:
microdontia
gingival hyperplasia
widely-spaced teeth
pointed teeth

Genitourinary Bladder:
vesicoureteral reflux

Growth Other:
overgrowth

Head And Neck Mouth:
triangular mouth
high-arched palate
small mouth
downturned corners of the mouth

Head And Neck Eyes:
upslanting palpebral fissures
cortical blindness
widely spaced eyes

Genitourinary External Genitalia Male:
small penis

Prenatal Manifestations Amniotic Fluid:
polyhydramnios (in some patients)
fetal hydrops (in some patients)

Cardiovascular Heart:
atrial septal defect (in some patients)

Abdomen Liver:
hepatomegaly (1 family)
cirrhosis (1 family)
iron deposition (1 family)

Skin Nails Hair Skin:
ichthyosis (1 family)
seborrheic dermatitis (1 family)
linear plaque-like scales (1 family)
pigmentation abnormalities (1 family)

Head And Neck Neck:
short neck

Head And Neck Nose:
depressed nasal bridge
short, anteverted nose

Skeletal Skull:
prominent occiput
enlarged fontanel

Head And Neck Ears:
overfolded helix
deafness

Neurologic Central Nervous System:
hypsarrhythmia
epileptic encephalopathy
delayed myelination
neuronal loss
cortical atrophy
more
Skin Nails Hair Nails:
hypoplastic nails

Skeletal:
joint contractures

Head And Neck Head:
microcephaly (in some patients)
increased head circumference (in some patients)
deceleration of head growth

Growth Weight:
high birth weight (in some patients)

Growth Height:
long birth length (in some patients)

Genitourinary Kidneys:
duplicated collecting system (1 patient)

Laboratory Abnormalities:
increased serum alkaline phosphatase (in some patients)


Clinical features from OMIM:

300868

Human phenotypes related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2:

32 (show top 50) (show all 52)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 32 HP:0000256
2 malar flattening 32 HP:0000272
3 hypertelorism 32 HP:0000316
4 short neck 32 HP:0000470
5 high palate 32 HP:0000218
6 hyperreflexia 32 HP:0001347
7 gingival overgrowth 32 HP:0000212
8 coarse facial features 32 HP:0000280
9 hearing impairment 32 HP:0000365
10 widely spaced teeth 32 HP:0000687
11 hepatomegaly 32 occasional (7.5%) HP:0002240
12 depressed nasal bridge 32 HP:0005280
13 anteverted nares 32 HP:0000463
14 ichthyosis 32 occasional (7.5%) HP:0008064
15 flexion contracture 32 HP:0001371
16 micrognathia 32 HP:0000347
17 generalized myoclonic seizures 32 HP:0002123
18 microdontia 32 HP:0000691
19 absent speech 32 HP:0001344
20 prominent occiput 32 HP:0000269
21 atrial septal defect 32 HP:0001631
22 cirrhosis 32 occasional (7.5%) HP:0001394
23 cerebral cortical atrophy 32 HP:0002120
24 cerebellar hypoplasia 32 HP:0001321
25 small nail 32 HP:0001792
26 narrow mouth 32 HP:0000160
27 upslanted palpebral fissure 32 HP:0000582
28 downturned corners of mouth 32 HP:0002714
29 vesicoureteral reflux 32 occasional (7.5%) HP:0000076
30 overfolded helix 32 HP:0000396
31 polyhydramnios 32 occasional (7.5%) HP:0001561
32 seborrheic dermatitis 32 occasional (7.5%) HP:0001051
33 large fontanelles 32 HP:0000239
34 absent septum pellucidum 32 HP:0001331
35 large for gestational age 32 HP:0001520
36 hypoplasia of the corpus callosum 32 HP:0002079
37 micropenis 32 HP:0000054
38 postnatal microcephaly 32 HP:0005484
39 abnormality of the pons 32 HP:0007361
40 overgrowth 32 HP:0001548
41 hypsarrhythmia 32 HP:0002521
42 epileptic encephalopathy 32 HP:0200134
43 elevated alkaline phosphatase 32 occasional (7.5%) HP:0003155
44 neuronal loss in central nervous system 32 HP:0002529
45 duplicated collecting system 32 occasional (7.5%) HP:0000081
46 cortical visual impairment 32 HP:0100704
47 central hypotonia 32 HP:0011398
48 muscular hypotonia of the trunk 32 HP:0008936
49 delayed myelination 32 HP:0012448
50 triangular mouth 32 HP:0000207

UMLS symptoms related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2:


myoclonic seizures

Drugs & Therapeutics for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

Search Clinical Trials , NIH Clinical Center for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

Genetic Tests for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

Genetic tests related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2:

# Genetic test Affiliating Genes
1 Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2 29 PIGA

Anatomical Context for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

MalaCards organs/tissues related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2:

41
Heart, Pons, Brain, Eye, Cerebellum, Olfactory Bulb

Publications for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

Articles related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2:

# Title Authors Year
1
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. ( 29974678 )
2018

Variations for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

UniProtKB/Swiss-Prot genetic disease variations for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2:

75
# Symbol AA change Variation ID SNP ID
1 PIGA p.Arg77Leu VAR_071069 rs587777398
2 PIGA p.Pro93Leu VAR_071070 rs587777400
3 PIGA p.Arg119Trp VAR_071071 rs587777396
4 PIGA p.Ile206Phe VAR_071072 rs201119959

ClinVar genetic disease variations for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2:

6
(show top 50) (show all 58)
# Gene Variation Type Significance SNP ID Assembly Location
1 PIGA NM_002641.3(PIGA): c.1234C> T (p.Arg412Ter) single nucleotide variant Pathogenic rs387906726 GRCh37 Chromosome X, 15339849: 15339849
2 PIGA NM_002641.3(PIGA): c.1234C> T (p.Arg412Ter) single nucleotide variant Pathogenic rs387906726 GRCh38 Chromosome X, 15321727: 15321727
3 PIGA NM_002641.3(PIGA): c.355C> T (p.Arg119Trp) single nucleotide variant Likely pathogenic rs587777396 GRCh37 Chromosome X, 15349698: 15349698
4 PIGA NM_002641.3(PIGA): c.355C> T (p.Arg119Trp) single nucleotide variant Likely pathogenic rs587777396 GRCh38 Chromosome X, 15331576: 15331576
5 PIGA NM_002641.3(PIGA): c.76dupT (p.Tyr26Leufs) duplication Pathogenic rs587777397 GRCh37 Chromosome X, 15349977: 15349977
6 PIGA NM_002641.3(PIGA): c.76dupT (p.Tyr26Leufs) duplication Pathogenic rs587777397 GRCh38 Chromosome X, 15331855: 15331855
7 PIGA NM_002641.3(PIGA): c.230G> T (p.Arg77Leu) single nucleotide variant Pathogenic rs587777398 GRCh37 Chromosome X, 15349823: 15349823
8 PIGA NM_002641.3(PIGA): c.230G> T (p.Arg77Leu) single nucleotide variant Pathogenic rs587777398 GRCh38 Chromosome X, 15331701: 15331701
9 PIGA NM_002641.3(PIGA): c.616A> T (p.Ile206Phe) single nucleotide variant Pathogenic rs201119959 GRCh37 Chromosome X, 15349437: 15349437
10 PIGA NM_002641.3(PIGA): c.616A> T (p.Ile206Phe) single nucleotide variant Pathogenic rs201119959 GRCh38 Chromosome X, 15331315: 15331315
11 PIGA NM_002641.3(PIGA): c.1030_1032delCTT (p.Leu344del) deletion Pathogenic rs587777399 GRCh37 Chromosome X, 15342943: 15342945
12 PIGA NM_002641.3(PIGA): c.1030_1032delCTT (p.Leu344del) deletion Pathogenic rs587777399 GRCh38 Chromosome X, 15324821: 15324823
13 PIGA NM_002641.3(PIGA): c.278C> T (p.Pro93Leu) single nucleotide variant Pathogenic rs587777400 GRCh37 Chromosome X, 15349775: 15349775
14 PIGA NM_002641.3(PIGA): c.278C> T (p.Pro93Leu) single nucleotide variant Pathogenic rs587777400 GRCh38 Chromosome X, 15331653: 15331653
15 PIGA NM_002641.3(PIGA): c.716-10A> G single nucleotide variant Benign/Likely benign rs375371562 GRCh37 Chromosome X, 15344178: 15344178
16 PIGA NM_002641.3(PIGA): c.716-10A> G single nucleotide variant Benign/Likely benign rs375371562 GRCh38 Chromosome X, 15326056: 15326056
17 PIGA NM_002641.3(PIGA): c.273C> T (p.Tyr91=) single nucleotide variant Benign/Likely benign rs61730284 GRCh37 Chromosome X, 15349780: 15349780
18 PIGA NM_002641.3(PIGA): c.273C> T (p.Tyr91=) single nucleotide variant Benign/Likely benign rs61730284 GRCh38 Chromosome X, 15331658: 15331658
19 PIGA NM_002641.3(PIGA): c.55C> T (p.Arg19Trp) single nucleotide variant Benign rs34422225 GRCh37 Chromosome X, 15349998: 15349998
20 PIGA NM_002641.3(PIGA): c.55C> T (p.Arg19Trp) single nucleotide variant Benign rs34422225 GRCh38 Chromosome X, 15331876: 15331876
21 PIGA NM_002641.3(PIGA): c.1214C> T (p.Ala405Val) single nucleotide variant Benign/Likely benign rs201361742 GRCh37 Chromosome X, 15339869: 15339869
22 PIGA NM_002641.3(PIGA): c.1214C> T (p.Ala405Val) single nucleotide variant Benign/Likely benign rs201361742 GRCh38 Chromosome X, 15321747: 15321747
23 PIGA NM_002641.3(PIGA): c.395C> G (p.Ser132Cys) single nucleotide variant Likely pathogenic rs1060499625 GRCh37 Chromosome X, 15349658: 15349658
24 PIGA NM_002641.3(PIGA): c.395C> G (p.Ser132Cys) single nucleotide variant Likely pathogenic rs1060499625 GRCh38 Chromosome X, 15331536: 15331536
25 PIGA NM_020473.3(PIGA): c.481G> A (p.Glu161Lys) single nucleotide variant Likely pathogenic rs1060499666 GRCh37 Chromosome X, 15342792: 15342792
26 PIGA NM_020473.3(PIGA): c.481G> A (p.Glu161Lys) single nucleotide variant Likely pathogenic rs1060499666 GRCh38 Chromosome X, 15324670: 15324670
27 PIGA NM_002641.3(PIGA): c.307G> A (p.Ala103Thr) single nucleotide variant Uncertain significance rs777795093 GRCh38 Chromosome X, 15331624: 15331624
28 PIGA NM_002641.3(PIGA): c.307G> A (p.Ala103Thr) single nucleotide variant Uncertain significance rs777795093 GRCh37 Chromosome X, 15349746: 15349746
29 PIGA NM_002641.3(PIGA): c.877A> G (p.Lys293Glu) single nucleotide variant Uncertain significance rs202161781 GRCh37 Chromosome X, 15343246: 15343246
30 PIGA NM_002641.3(PIGA): c.877A> G (p.Lys293Glu) single nucleotide variant Uncertain significance rs202161781 GRCh38 Chromosome X, 15325124: 15325124
31 PIGA NM_002641.3(PIGA): c.1048C> T (p.Pro350Ser) single nucleotide variant Uncertain significance rs372966902 GRCh38 Chromosome X, 15324805: 15324805
32 PIGA NM_002641.3(PIGA): c.1048C> T (p.Pro350Ser) single nucleotide variant Uncertain significance rs372966902 GRCh37 Chromosome X, 15342927: 15342927
33 PIGA NM_002641.3(PIGA): c.348A> G (p.Ile116Met) single nucleotide variant Uncertain significance GRCh38 Chromosome X, 15331583: 15331583
34 PIGA NM_002641.3(PIGA): c.348A> G (p.Ile116Met) single nucleotide variant Uncertain significance GRCh37 Chromosome X, 15349705: 15349705
35 PIGA NM_002641.3(PIGA): c.525T> C (p.Leu175=) single nucleotide variant Benign rs61751426 GRCh38 Chromosome X, 15331406: 15331406
36 PIGA NM_002641.3(PIGA): c.525T> C (p.Leu175=) single nucleotide variant Benign rs61751426 GRCh37 Chromosome X, 15349528: 15349528
37 PIGA NM_002641.3(PIGA): c.56G> A (p.Arg19Gln) single nucleotide variant Likely pathogenic GRCh37 Chromosome X, 15349997: 15349997
38 PIGA NM_002641.3(PIGA): c.56G> A (p.Arg19Gln) single nucleotide variant Likely pathogenic GRCh38 Chromosome X, 15331875: 15331875
39 PIGA NM_002641.3(PIGA): c.1420G> A (p.Gly474Arg) single nucleotide variant Benign/Likely benign rs61760986 GRCh37 Chromosome X, 15339663: 15339663
40 PIGA NM_002641.3(PIGA): c.1420G> A (p.Gly474Arg) single nucleotide variant Benign/Likely benign rs61760986 GRCh38 Chromosome X, 15321541: 15321541
41 PIGA NM_002641.3(PIGA): c.981+8G> A single nucleotide variant Benign/Likely benign rs778602062 GRCh37 Chromosome X, 15343134: 15343134
42 PIGA NM_002641.3(PIGA): c.981+8G> A single nucleotide variant Benign/Likely benign rs778602062 GRCh38 Chromosome X, 15325012: 15325012
43 PIGA NM_002641.3(PIGA): c.982-4T> A single nucleotide variant Likely benign GRCh37 Chromosome X, 15342997: 15342997
44 PIGA NM_002641.3(PIGA): c.982-4T> A single nucleotide variant Likely benign GRCh38 Chromosome X, 15324875: 15324875
45 PIGA NM_002641.3(PIGA): c.982-9delC deletion Likely benign GRCh37 Chromosome X, 15343002: 15343002
46 PIGA NM_002641.3(PIGA): c.982-9delC deletion Likely benign GRCh38 Chromosome X, 15324880: 15324880
47 PIGA NM_002641.3(PIGA): c.1422G> A (p.Gly474=) single nucleotide variant Likely benign GRCh37 Chromosome X, 15339661: 15339661
48 PIGA NM_002641.3(PIGA): c.1422G> A (p.Gly474=) single nucleotide variant Likely benign GRCh38 Chromosome X, 15321539: 15321539
49 PIGA NM_002641.3(PIGA): c.1447A> G (p.Thr483Ala) single nucleotide variant Uncertain significance rs745560847 GRCh38 Chromosome X, 15321514: 15321514
50 PIGA NM_002641.3(PIGA): c.1447A> G (p.Thr483Ala) single nucleotide variant Uncertain significance rs745560847 GRCh37 Chromosome X, 15339636: 15339636

Expression for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

Search GEO for disease gene expression data for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2.

Pathways for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

GO Terms for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

Cellular components related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 anchored component of membrane GO:0031225 9.16 CD55 CD59
2 transport vesicle GO:0030133 8.96 CD55 CD59
3 endoplasmic reticulum-Golgi intermediate compartment membrane GO:0033116 8.62 CD55 CD59

Biological processes related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neutrophil degranulation GO:0043312 9.16 CD55 CD59
2 ER to Golgi vesicle-mediated transport GO:0006888 8.96 CD55 CD59
3 regulation of complement activation GO:0030449 8.62 CD55 CD59

Sources for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2

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