MCID: MLT126
MIFTS: 33

Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

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

Aliases & Classifications for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

MalaCards integrated aliases for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1:

Name: Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1 57 12 75 29 13 6 15 73
Glycosylphosphatidylinositol Biosynthesis Defect 3 57 75
Mcahs1 57 75
Gpibd3 57 75
Multiple Congenital Anomalies, Hypotonia, Seizures Syndrome, Type 1 ) 40
Congenital Disorder of Glycosylation Due to Pign Deficiency 59
Glycosylphosphatidylinositol Biosynthesis Defect 3; Gpibd3 57
Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 59
Pign-Cdg 59

Characteristics:

Orphanet epidemiological data:

59
multiple congenital anomalies-hypotonia-seizures syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset at birth or in utero


HPO:

32
multiple congenital anomalies-hypotonia-seizures syndrome 1:
Onset and clinical course variable expressivity congenital onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

OMIM : 57 Multiple congenital anomalies-hypotonia-seizures syndrome is an autosomal recessive disorder characterized by neonatal hypotonia, lack of psychomotor development, seizures, dysmorphic features, and variable congenital anomalies involving the cardiac, urinary, and gastrointestinal systems. Most affected individuals die before 3 years of age (summary by Maydan et al., 2011). The disorder is caused by a defect in glycosylphosphatidylinositol biosynthesis; see GPIBD1 (610293). (614080)

MalaCards based summary : Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1, also known as glycosylphosphatidylinositol biosynthesis defect 3, is related to multiple congenital anomalies-hypotonia-seizures syndrome 2 and multiple congenital anomalies-hypotonia-seizures syndrome 3, and has symptoms including muscle spasticity, seizures and tremor. An important gene associated with Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1 is PIGN (Phosphatidylinositol Glycan Anchor Biosynthesis Class N). Affiliated tissues include lung, kidney and eye, and related phenotypes are macrocephaly and hypertelorism

UniProtKB/Swiss-Prot : 75 Multiple congenital anomalies-hypotonia-seizures syndrome 1: An autosomal recessive disorder characterized by neonatal hypotonia, lack of psychomotor development, seizures, dysmorphic features, and variable congenital anomalies involving the cardiac, urinary, and gastrointestinal systems. Most affected individuals die before 3 years of age.

Related Diseases for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

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

Diseases related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 multiple congenital anomalies-hypotonia-seizures syndrome 2 12.9
2 multiple congenital anomalies-hypotonia-seizures syndrome 3 12.9
3 multiple congenital anomalies-hypotonia-seizures syndrome 11.9
4 hypotonia 10.3

Symptoms & Phenotypes for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
nystagmus
epicanthal folds
wandering eyes

Head And Neck Face:
frontal bossing
long philtrum
micrognathia
coarse facies
bitemporal narrowing

Head And Neck Nose:
depressed nasal bridge
small nose
upturned nares

Head And Neck Mouth:
cleft palate
open mouth
high-arched palate
thin lips

Cardiovascular Heart:
atrial septal defect
persistent foramen ovale

Genitourinary Kidneys:
hydronephrosis
hydrocele
dysplastic kidney (in some patients)

Growth Weight:
increased birth weight

Skeletal Feet:
hypoplasia of the distal phalanges

Head And Neck Head:
macrocephaly (2 patients)
prominent sutures

Genitourinary Ureters:
hypoplasia of the ureter (1 patient)
redundant ureter (1 patient)

Skeletal Pelvis:
narrow inferior iliacs

Laboratory Abnormalities:
decreased expression of gpi-anchored proteins

Head And Neck Ears:
low-set ears
posteriorly rotated ears
cupped ears
overfolded helices
large, fleshy ears

Neurologic Central Nervous System:
intellectual disability
seizures
spasticity
tremor
hyperreflexia
more
Abdomen Gastrointestinal:
gastroesophageal reflux
anal stenosis
imperforate anus

Cardiovascular Vascular:
patent ductus arteriosus

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Muscle Soft Tissue:
hypotonia

Skeletal Hands:
hypoplasia of the distal phalanges

Chest Diaphragm:
diaphragmatic hernia (in some patients)

Respiratory Lung:
lung hypoplasia (in some patients)

Genitourinary Bladder:
vesicoureteral reflux (1 patient)
trabecular bladder (2 patients)

Skin Nails Hair Skin:
deep plantar crease


Clinical features from OMIM:

614080

Human phenotypes related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1:

32 (show all 46)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 32 frequent (33%) HP:0000256
2 hypertelorism 32 HP:0000316
3 low-set ears 32 HP:0000369
4 frontal bossing 32 HP:0002007
5 high palate 32 HP:0000218
6 nystagmus 32 HP:0000639
7 intellectual disability 32 HP:0001249
8 seizures 32 HP:0001250
9 spasticity 32 HP:0001257
10 tremor 32 HP:0001337
11 hyperreflexia 32 frequent (33%) HP:0001347
12 coarse facial features 32 HP:0000280
13 global developmental delay 32 HP:0001263
14 depressed nasal bridge 32 HP:0005280
15 short nose 32 HP:0003196
16 anteverted nares 32 HP:0000463
17 gastroesophageal reflux 32 HP:0002020
18 cleft palate 32 HP:0000175
19 long philtrum 32 HP:0000343
20 micrognathia 32 HP:0000347
21 patent ductus arteriosus 32 HP:0001643
22 epicanthus 32 HP:0000286
23 absent speech 32 HP:0001344
24 atrial septal defect 32 HP:0001631
25 open mouth 32 HP:0000194
26 anal atresia 32 HP:0002023
27 vesicoureteral reflux 32 occasional (7.5%) HP:0000076
28 overfolded helix 32 HP:0000396
29 polyhydramnios 32 HP:0001561
30 amblyopia 32 HP:0000646
31 hyporeflexia 32 HP:0001265
32 choreoathetosis 32 frequent (33%) HP:0001266
33 thin vermilion border 32 HP:0000233
34 short distal phalanx of finger 32 HP:0009882
35 hydronephrosis 32 HP:0000126
36 cerebellar atrophy 32 occasional (7.5%) HP:0001272
37 congenital diaphragmatic hernia 32 occasional (7.5%) HP:0000776
38 cerebral atrophy 32 HP:0002059
39 cupped ear 32 HP:0000378
40 anal stenosis 32 HP:0002025
41 pulmonary hypoplasia 32 occasional (7.5%) HP:0002089
42 generalized hypotonia 32 HP:0001290
43 posteriorly rotated ears 32 HP:0000358
44 hydrocele testis 32 HP:0000034
45 narrow forehead 32 HP:0000341
46 large fleshy ears 32 HP:0002265

UMLS symptoms related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1:


muscle spasticity, seizures, tremor

Drugs & Therapeutics for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

Search Clinical Trials , NIH Clinical Center for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

Genetic Tests for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

Genetic tests related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1:

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

Anatomical Context for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

MalaCards organs/tissues related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1:

41
Lung, Kidney, Eye, Testis

Publications for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

Articles related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1:

# Title Authors Year
1
The phenotype of multiple congenital anomalies-hypotonia-seizures syndrome 1: report and review. ( 25920937 )
2015
2
A PIGN mutation responsible for multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1) in an Israeli-Arab family. ( 26364997 )
2015

Variations for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

UniProtKB/Swiss-Prot genetic disease variations for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1:

75
# Symbol AA change Variation ID SNP ID
1 PIGN p.Arg709Gln VAR_066402 rs397514475

ClinVar genetic disease variations for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1:

6
(show top 50) (show all 169)
# Gene Variation Type Significance SNP ID Assembly Location
1 PIGN NM_176787.4(PIGN): c.2126G> A (p.Arg709Gln) single nucleotide variant Pathogenic rs397514475 GRCh37 Chromosome 18, 59763135: 59763135
2 PIGN NM_176787.4(PIGN): c.2126G> A (p.Arg709Gln) single nucleotide variant Pathogenic rs397514475 GRCh38 Chromosome 18, 62095902: 62095902
3 PIGN NM_176787.4(PIGN): c.808T> C (p.Ser270Pro) single nucleotide variant Pathogenic rs587777186 GRCh38 Chromosome 18, 62146023: 62146023
4 PIGN NM_176787.4(PIGN): c.808T> C (p.Ser270Pro) single nucleotide variant Pathogenic rs587777186 GRCh37 Chromosome 18, 59813256: 59813256
5 PIGN NM_176787.4(PIGN): c.963G> A (p.Gln321=) single nucleotide variant Pathogenic rs587777187 GRCh38 Chromosome 18, 62143306: 62143306
6 PIGN NM_176787.4(PIGN): c.963G> A (p.Gln321=) single nucleotide variant Pathogenic rs587777187 GRCh37 Chromosome 18, 59810539: 59810539
7 PIGN NM_176787.4(PIGN): c.364G> C (p.Glu122Gln) single nucleotide variant Uncertain significance rs200756305 GRCh38 Chromosome 18, 62157207: 62157207
8 PIGN NM_176787.4(PIGN): c.364G> C (p.Glu122Gln) single nucleotide variant Uncertain significance rs200756305 GRCh37 Chromosome 18, 59824440: 59824440
9 PIGN NM_176787.4(PIGN): c.755A> T (p.Asp252Val) single nucleotide variant Pathogenic rs886039216 GRCh37 Chromosome 18, 59814254: 59814254
10 PIGN NM_176787.4(PIGN): c.755A> T (p.Asp252Val) single nucleotide variant Pathogenic rs886039216 GRCh38 Chromosome 18, 62147021: 62147021
11 PIGN NM_176787.4(PIGN): c.2340T> A (p.Tyr780Ter) single nucleotide variant Pathogenic rs749334082 GRCh37 Chromosome 18, 59756019: 59756019
12 PIGN NM_176787.4(PIGN): c.2340T> A (p.Tyr780Ter) single nucleotide variant Pathogenic rs749334082 GRCh38 Chromosome 18, 62088786: 62088786
13 PIGN NM_176787.4(PIGN): c.1434+5G> A single nucleotide variant Pathogenic rs369486176 GRCh37 Chromosome 18, 59780362: 59780362
14 PIGN NM_176787.4(PIGN): c.1434+5G> A single nucleotide variant Pathogenic rs369486176 GRCh38 Chromosome 18, 62113129: 62113129
15 PIGN NM_176787.4(PIGN): c.548_549+6delAGGTTTGT deletion Pathogenic/Likely pathogenic rs779636222 GRCh37 Chromosome 18, 59821772: 59821779
16 PIGN NM_176787.4(PIGN): c.548_549+6delAGGTTTGT deletion Pathogenic/Likely pathogenic rs779636222 GRCh38 Chromosome 18, 62154539: 62154546
17 PIGN NC_000018.9: g.59821582_59824939del deletion Pathogenic GRCh37 Chromosome 18, 59821582: 59824939
18 PIGN NM_176787.4(PIGN): c.1966C> T (p.Gln656Ter) single nucleotide variant Pathogenic rs886039217 GRCh38 Chromosome 18, 62102796: 62102796
19 PIGN NM_176787.4(PIGN): c.1966C> T (p.Gln656Ter) single nucleotide variant Pathogenic rs886039217 GRCh37 Chromosome 18, 59770029: 59770029
20 PIGN NM_176787.4(PIGN): c.1674+1G> C single nucleotide variant Pathogenic rs376355678 GRCh38 Chromosome 18, 62106985: 62106985
21 PIGN NM_176787.4(PIGN): c.1674+1G> C single nucleotide variant Pathogenic rs376355678 GRCh37 Chromosome 18, 59774218: 59774218
22 PIGN NM_176787.4(PIGN): c.694A> T (p.Lys232Ter) single nucleotide variant Pathogenic rs886039218 GRCh38 Chromosome 18, 62147082: 62147082
23 PIGN NM_176787.4(PIGN): c.694A> T (p.Lys232Ter) single nucleotide variant Pathogenic rs886039218 GRCh37 Chromosome 18, 59814315: 59814315
24 PIGN NM_176787.4(PIGN): c.996T> G (p.Ile332Met) single nucleotide variant Pathogenic/Likely pathogenic rs1060499763 GRCh38 Chromosome 18, 62140447: 62140447
25 PIGN NM_176787.4(PIGN): c.996T> G (p.Ile332Met) single nucleotide variant Pathogenic/Likely pathogenic rs1060499763 GRCh37 Chromosome 18, 59807680: 59807680
26 PIGN NM_176787.4(PIGN): c.741C> T (p.His247=) single nucleotide variant Benign rs9320000 GRCh37 Chromosome 18, 59814268: 59814268
27 PIGN NM_176787.4(PIGN): c.741C> T (p.His247=) single nucleotide variant Benign rs9320000 GRCh38 Chromosome 18, 62147035: 62147035
28 PIGN NM_176787.4(PIGN): c.685C> G (p.His229Asp) single nucleotide variant Benign rs9320001 GRCh38 Chromosome 18, 62147091: 62147091
29 PIGN NM_176787.4(PIGN): c.685C> G (p.His229Asp) single nucleotide variant Benign rs9320001 GRCh37 Chromosome 18, 59814324: 59814324
30 PIGN NM_176787.4(PIGN): c.932T> G (p.Leu311Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs746882521 GRCh37 Chromosome 18, 59810570: 59810570
31 PIGN NM_176787.4(PIGN): c.932T> G (p.Leu311Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs746882521 GRCh38 Chromosome 18, 62143337: 62143337
32 PIGN NM_176787.4(PIGN): c.421dup (p.Ile141Asnfs) duplication Pathogenic GRCh38 Chromosome 18, 62157150: 62157150
33 PIGN NM_176787.4(PIGN): c.421dup (p.Ile141Asnfs) duplication Pathogenic GRCh37 Chromosome 18, 59824383: 59824383
34 PIGN NG_033144.1: g.34356_39420del5065 deletion Pathogenic GRCh38 Chromosome 18, 62152637: 62157701
35 PIGN NG_033144.1: g.34356_39420del5065 deletion Pathogenic GRCh37 Chromosome 18, 59819870: 59824934
36 PIGN NM_176787.4(PIGN): c.167C> T (p.Ala56Val) single nucleotide variant Benign rs61755362 GRCh37 Chromosome 18, 59828420: 59828420
37 PIGN NM_176787.4(PIGN): c.167C> T (p.Ala56Val) single nucleotide variant Benign rs61755362 GRCh38 Chromosome 18, 62161187: 62161187
38 PIGN NM_176787.4(PIGN): c.2567C> T (p.Ser856Leu) single nucleotide variant Uncertain significance rs780781469 GRCh38 Chromosome 18, 62082682: 62082682
39 PIGN NM_176787.4(PIGN): c.2567C> T (p.Ser856Leu) single nucleotide variant Uncertain significance rs780781469 GRCh37 Chromosome 18, 59749915: 59749915
40 PIGN NM_176787.4(PIGN): c.2411_2412delTAinsAG (p.Ile804Lys) indel Uncertain significance GRCh38 Chromosome 18, 62085223: 62085224
41 PIGN NM_176787.4(PIGN): c.2411_2412delTAinsAG (p.Ile804Lys) indel Uncertain significance GRCh37 Chromosome 18, 59752456: 59752457
42 PIGN NM_176787.4(PIGN): c.776T> C (p.Phe259Ser) single nucleotide variant Uncertain significance rs370310838 GRCh38 Chromosome 18, 62147000: 62147000
43 PIGN NM_176787.4(PIGN): c.776T> C (p.Phe259Ser) single nucleotide variant Uncertain significance rs370310838 GRCh37 Chromosome 18, 59814233: 59814233
44 PIGN NM_176787.4(PIGN): c.2783G> A (p.Ser928Asn) single nucleotide variant Likely benign rs201397391 GRCh37 Chromosome 18, 59713102: 59713102
45 PIGN NM_176787.4(PIGN): c.2783G> A (p.Ser928Asn) single nucleotide variant Likely benign rs201397391 GRCh38 Chromosome 18, 62045869: 62045869
46 PIGN NM_176787.4(PIGN): c.2745C> G (p.Leu915=) single nucleotide variant Likely benign rs764309084 GRCh38 Chromosome 18, 62045907: 62045907
47 PIGN NM_176787.4(PIGN): c.2745C> G (p.Leu915=) single nucleotide variant Likely benign rs764309084 GRCh37 Chromosome 18, 59713140: 59713140
48 PIGN NM_176787.4(PIGN): c.2590G> A (p.Val864Ile) single nucleotide variant Uncertain significance rs966106333 GRCh37 Chromosome 18, 59742041: 59742041
49 PIGN NM_176787.4(PIGN): c.2590G> A (p.Val864Ile) single nucleotide variant Uncertain significance rs966106333 GRCh38 Chromosome 18, 62074808: 62074808
50 PIGN NM_176787.4(PIGN): c.1926A> G (p.Lys642=) single nucleotide variant Likely benign rs760848888 GRCh37 Chromosome 18, 59770069: 59770069

Expression for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

Search GEO for disease gene expression data for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1.

Pathways for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

GO Terms for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

Cellular components related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum membrane GO:0005789 8.62 CD59 PIGN

Sources for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 1

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