MCAHS4
MCID: MLT179
MIFTS: 26

Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4 (MCAHS4)

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 4

MalaCards integrated aliases for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4:

Name: Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4 57
Glycosylphosphatidylinositol Biosynthesis Defect 19 57 12 72
Gpibd19 57 12 72
Developmental and Epileptic Encephalopathy, 77 29 6
Developmental and Epileptic Encephalopathy 77 57 12
Epileptic Encephalopathy, Early Infantile, 77 57 72
Mcahs4 57 12
Eiee77 57 72
Dee77 57 12
Glycosylphosphatidylinositol Biosynthesis Defect 19; Gpibd19 57
Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome-4 12
Epileptic Encephalopathy, Early Infantile, 77; Eiee77 57
Developmental and Epileptic Encephalopathy 77; Dee77 57
Early Infantile Epileptic Encephalopathy 77 12

Characteristics:

OMIM®:

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

Miscellaneous:
onset in infancy
early death may occur
three unrelated patients have been reported (last curated august 2019)


HPO:

31
multiple congenital anomalies-hypotonia-seizures syndrome 4:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

OMIM® : 57 Multiple congenital anomalies-hypotonia-seizures syndrome-4 (MCAHS4) is an autosomal recessive neurologic disorder characterized by onset of refractory seizures in the first months of life. Patients have severe global developmental delay, and may have additional variable features, including dysmorphic or coarse facial features, visual defects, and mild skeletal or renal anomalies. At the cellular level, the disorder is caused by a defect in the synthesis of glycosylphosphatidylinositol (GPI), and thus affects the expression of GPI-anchored proteins at the cell surface (summary by Starr et al., 2019). For a discussion of genetic heterogeneity of MCAHS, see MCAHS1 (614080). For a discussion of genetic heterogeneity of DEE, see 308350. For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293). (618548) (Updated 05-Apr-2021)

MalaCards based summary : Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4, is also known as glycosylphosphatidylinositol biosynthesis defect 19. An important gene associated with Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4 is PIGQ (Phosphatidylinositol Glycan Anchor Biosynthesis Class Q). Affiliated tissues include heart, and related phenotypes are scoliosis and ptosis

Disease Ontology : 12 A developmental and epileptic encephalopathy characterized by onset in the first months of life of refractory seizures and severe global developmental delay that has material basis in homozygous or compound heterozygous mutation in PIGQ on chromosome 16p13.3.

UniProtKB/Swiss-Prot : 72 Epileptic encephalopathy, early infantile, 77: A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE77 is an autosomal recessive form characterized by onset of refractory seizures in the first months of life. Additional clinical features include coarse, dysmorphic facial features, and skeletal, renal and ophthalmic anomalies. At the cellular level, the disorder is caused by a defect in the synthesis of glycosylphosphatidylinositol (GPI).

Related Diseases for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

Symptoms & Phenotypes for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

Human phenotypes related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4:

31 (show all 35)
# Description HPO Frequency HPO Source Accession
1 scoliosis 31 very rare (1%) HP:0002650
2 ptosis 31 very rare (1%) HP:0000508
3 coarse facial features 31 very rare (1%) HP:0000280
4 inguinal hernia 31 very rare (1%) HP:0000023
5 smooth philtrum 31 very rare (1%) HP:0000319
6 feeding difficulties in infancy 31 very rare (1%) HP:0008872
7 full cheeks 31 very rare (1%) HP:0000293
8 micrognathia 31 very rare (1%) HP:0000347
9 pectus excavatum 31 very rare (1%) HP:0000767
10 downturned corners of mouth 31 very rare (1%) HP:0002714
11 polyhydramnios 31 very rare (1%) HP:0001561
12 vesicoureteral reflux 31 very rare (1%) HP:0000076
13 thin upper lip vermilion 31 very rare (1%) HP:0000219
14 long philtrum 31 very rare (1%) HP:0000343
15 ventriculomegaly 31 very rare (1%) HP:0002119
16 telecanthus 31 very rare (1%) HP:0000506
17 wide anterior fontanel 31 very rare (1%) HP:0000260
18 plagiocephaly 31 very rare (1%) HP:0001357
19 diastasis recti 31 very rare (1%) HP:0001540
20 astigmatism 31 very rare (1%) HP:0000483
21 poor head control 31 very rare (1%) HP:0002421
22 deep plantar creases 31 very rare (1%) HP:0001869
23 alacrima 31 very rare (1%) HP:0000522
24 broad nasal tip 31 very rare (1%) HP:0000455
25 abdominal wall muscle weakness 31 very rare (1%) HP:0009023
26 cerebral visual impairment 31 very rare (1%) HP:0100704
27 uplifted earlobe 31 very rare (1%) HP:0009909
28 soft skin 31 very rare (1%) HP:0000977
29 infantile muscular hypotonia 31 very rare (1%) HP:0008947
30 elevated alkaline phosphatase 31 very rare (1%) HP:0003155
31 vertical nystagmus 31 very rare (1%) HP:0010544
32 renal cortical cysts 31 very rare (1%) HP:0000803
33 multifocal seizures 31 very rare (1%) HP:0031165
34 myoclonic seizure 31 very rare (1%) HP:0032794
35 hooded upper eyelid 31 very rare (1%) HP:0030822

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal Spine:
scoliosis

Muscle Soft Tissue:
inguinal hernia
hypotonia

Head And Neck Nose:
anteverted nares
broad nasal tip
thick alae nasi

Cardiovascular Heart:
heart block

Head And Neck Mouth:
downturned corners of the mouth
thin vermilion of the upper lip

Head And Neck Teeth:
delayed dentition

Head And Neck Ears:
fleshy ear lobes

Chest External Features:
pectus excavatum (patient a)

Genitourinary Bladder:
vesicoureteral reflux (patient a)

Skeletal Limbs:
transient cysts in the long bones (patient a)

Skin Nails Hair Skin:
soft, sagging skin

Laboratory Abnormalities:
increased serum alkaline phosphatase (patient a)

Head And Neck Eyes:
ptosis
optic atrophy
telecanthus
astigmatism
alacrima
more
Head And Neck Face:
smooth philtrum
full cheeks
micrognathia
long philtrum
coarse facial features (patient a)

Abdomen External Features:
diastasis recti
abdominal wall laxity

Neurologic Central Nervous System:
epileptic encephalopathy
delayed myelination
enlarged ventricles
seizures, refractory
global developmental delay, profound

Abdomen Gastrointestinal:
poor feeding

Head And Neck Head:
plagiocephaly (patient a)

Cardiovascular Vascular:
pulmonary hypertension (in 1 patient)

Genitourinary Kidneys:
renal cysts (patient a)

Skeletal Skull:
large anterior fontanel (patient a)
sphenoid wing dysplasia (patient a)

Skeletal Hands:
plantar creases

Prenatal Manifestations Amniotic Fluid:
polyhydramnios (patient a)

Clinical features from OMIM®:

618548 (Updated 05-Apr-2021)

Drugs & Therapeutics for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

Search Clinical Trials , NIH Clinical Center for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

Genetic Tests for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

Genetic tests related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4:

# Genetic test Affiliating Genes
1 Developmental and Epileptic Encephalopathy, 77 29 PIGQ

Anatomical Context for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

MalaCards organs/tissues related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4:

40
Heart

Publications for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

Articles related to Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4:

# Title Authors PMID Year
1
Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ: Report of seven new subjects and review of the literature. 57 6
32588908 2020
2
PIGQ glycosylphosphatidylinositol-anchored protein deficiency: Characterizing the phenotype. 6 57
31148362 2019
3
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. 57 6
25558065 2015
4
Clinical whole-genome sequencing in severe early-onset epilepsy reveals new genes and improves molecular diagnosis. 6 57
24463883 2014

Variations for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

ClinVar genetic disease variations for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PIGQ NM_004204.5(PIGQ):c.968_969del (p.Leu323fs) Deletion Pathogenic 520669 rs747661902 GRCh37: 16:628404-628405
GRCh38: 16:578404-578405
2 PIGQ NM_004204.5(PIGQ):c.1578_1579del (p.Arg527fs) Deletion Pathogenic 995848 GRCh37: 16:632294-632295
GRCh38: 16:582294-582295
3 PIGQ NM_004204.4(PIGQ):c.942+1G>A SNV Pathogenic 453003 rs200661329 GRCh37: 16:626255-626255
GRCh38: 16:576255-576255
4 PIGQ NM_004204.5(PIGQ):c.1199_1201del (p.Tyr400del) Deletion Pathogenic 449630 rs766667249 GRCh37: 16:628912-628914
GRCh38: 16:578912-578914
5 PIGQ NM_148920.3(PIGQ):c.690-2A>G SNV Pathogenic 140458 rs587777543 GRCh37: 16:625837-625837
GRCh38: 16:575837-575837
6 PIGQ NM_004204.4(PIGQ):c.619C>T (p.Arg207Ter) SNV Pathogenic/Likely pathogenic 183339 rs730882240 GRCh37: 16:624693-624693
GRCh38: 16:574693-574693

Expression for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

Search GEO for disease gene expression data for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4.

Pathways for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

GO Terms for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

Sources for Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 4

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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