SIHIWES
MCID: SFR001
MIFTS: 30

Sifrim-Hitz-Weiss Syndrome (SIHIWES)

Categories: Genetic diseases

Aliases & Classifications for Sifrim-Hitz-Weiss Syndrome

MalaCards integrated aliases for Sifrim-Hitz-Weiss Syndrome:

Name: Sifrim-Hitz-Weiss Syndrome 57 72 36 29 6 39
Sihiwes 57 72
Sifrim-Hitz-Weiss Multiple Congenital Anomalies-Mental Retardation Syndrome 57

Characteristics:

OMIM®:

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

Miscellaneous:
highly variable phenotype
mutations occur de novo


HPO:

31
sifrim-hitz-weiss syndrome:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Sifrim-Hitz-Weiss Syndrome

KEGG : 36 Sifrim-Hitz-Weiss syndrome is characterized by developmental delay, intellectual disability, hearing loss, macrocephaly, distinct facial dysmorphisms, palatal abnormalities, ventriculomegaly, and hypogonadism as well as additional findings such as bone fusions. It has been reported that de novo mutations in CHD4 cause this disease. CHD4 is a core component of the NuRD complex, which possesses both chromatin remodeling and histone deacetylation activities.

MalaCards based summary : Sifrim-Hitz-Weiss Syndrome, also known as sihiwes, is related to chd4 neurodevelopmental disorder and alacrima, achalasia, and mental retardation syndrome. An important gene associated with Sifrim-Hitz-Weiss Syndrome is CHD4 (Chromodomain Helicase DNA Binding Protein 4), and among its related pathways/superpathways is Chromatin Regulation / Acetylation. Affiliated tissues include heart, and related phenotypes are atrial septal defect and coarctation of aorta

OMIM® : 57 Sifrim-Hitz-Weiss syndrome is an autosomal dominant intellectual developmental disorder with variable congenital defects affecting other systems, including cardiac, skeletal, and urogenital. Some patients may have short stature, enlarged head circumference, hearing loss, and nonspecific dysmorphic facial features (summary by Sifrim et al., 2016 and Weiss et al., 2016). (617159) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Sifrim-Hitz-Weiss syndrome: An autosomal dominant syndrome characterized by mental retardation, variable congenital defects affecting cardiac, skeletal, and urogenital systems. Short stature, macrocephaly, hearing impairment, and facial dysmorphism are present in some patients.

Related Diseases for Sifrim-Hitz-Weiss Syndrome

Diseases related to Sifrim-Hitz-Weiss Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 chd4 neurodevelopmental disorder 11.5
2 alacrima, achalasia, and mental retardation syndrome 10.4

Symptoms & Phenotypes for Sifrim-Hitz-Weiss Syndrome

Human phenotypes related to Sifrim-Hitz-Weiss Syndrome:

31 (show all 33)
# Description HPO Frequency HPO Source Accession
1 atrial septal defect 31 very rare (1%) HP:0001631
2 coarctation of aorta 31 very rare (1%) HP:0001680
3 ventricular septal defect 31 very rare (1%) HP:0001629
4 short clavicles 31 very rare (1%) HP:0000894
5 macrocephaly 31 HP:0000256
6 intellectual disability 31 HP:0001249
7 ptosis 31 HP:0000508
8 coarse facial features 31 HP:0000280
9 hearing impairment 31 HP:0000365
10 hypertelorism 31 HP:0000316
11 short stature 31 HP:0004322
12 renal insufficiency 31 HP:0000083
13 cryptorchidism 31 HP:0000028
14 low-set ears 31 HP:0000369
15 epicanthus 31 HP:0000286
16 upslanted palpebral fissure 31 HP:0000582
17 micropenis 31 HP:0000054
18 tetralogy of fallot 31 HP:0001636
19 vesicoureteral reflux 31 HP:0000076
20 ventriculomegaly 31 HP:0002119
21 gait imbalance 31 HP:0002141
22 arnold-chiari malformation 31 HP:0002308
23 wormian bones 31 HP:0002645
24 ambiguous genitalia 31 HP:0000062
25 anteriorly placed anus 31 HP:0001545
26 tapered finger 31 HP:0001182
27 trigonocephaly 31 HP:0000243
28 astigmatism 31 HP:0000483
29 cupped ear 31 HP:0000378
30 generalized hypotonia 31 HP:0001290
31 short palpebral fissure 31 HP:0012745
32 flat acetabular roof 31 HP:0003180
33 short femoral neck 31 HP:0100864

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Head:
macrocephaly

Head And Neck Eyes:
ptosis
hypertelorism
astigmatism
epicanthal folds
short palpebral fissures
more
Growth Height:
short stature

Genitourinary External Genitalia Male:
cryptorchidism
micropenis
ambiguous genitalia

Genitourinary Bladder:
vesicoureteral reflux

Abdomen Gastrointestinal:
anteriorly placed anus

Skeletal Limbs:
short femoral neck

Head And Neck Face:
coarse facies

Chest Ribs Sternum Clavicles And Scapulae:
abnormal clavicles

Skeletal:
bony fusion

Skeletal Feet:
fusion of the foot bones

Neurologic Central Nervous System:
intellectual disability
gait imbalance
enlarged ventricles
chiari malformation
delayed global development

Head And Neck Ears:
hearing impairment
low-set ears
cupped ears
abnormally shaped ears

Genitourinary Kidneys:
renal insufficiency

Cardiovascular Heart:
tetralogy of fallot
septal defects
coarctation of the aorta
congenital heart defects

Skeletal Skull:
wormian bones
trigonocephaly
basal skull abnormalities

Skeletal Pelvis:
flat acetabular roof

Muscle Soft Tissue:
hypotonia

Skeletal Hands:
tapered fingers
fusion of the wrist bones

Head And Neck Mouth:
palatal abnormalities

Skeletal Spine:
cervical fusion

Endocrine Features:
hypogonadotropic hypogonadism (in males)

Clinical features from OMIM®:

617159 (Updated 05-Apr-2021)

Drugs & Therapeutics for Sifrim-Hitz-Weiss Syndrome

Search Clinical Trials , NIH Clinical Center for Sifrim-Hitz-Weiss Syndrome

Genetic Tests for Sifrim-Hitz-Weiss Syndrome

Genetic tests related to Sifrim-Hitz-Weiss Syndrome:

# Genetic test Affiliating Genes
1 Sifrim-Hitz-Weiss Syndrome 29 CHD4

Anatomical Context for Sifrim-Hitz-Weiss Syndrome

MalaCards organs/tissues related to Sifrim-Hitz-Weiss Syndrome:

40
Heart

Publications for Sifrim-Hitz-Weiss Syndrome

Articles related to Sifrim-Hitz-Weiss Syndrome:

# Title Authors PMID Year
1
De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an Intellectual Disability Syndrome with Distinctive Dysmorphisms. 57 6
27616479 2016
2
Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing. 57 6
27479907 2016
3
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 6
25741868 2015
4
[Clinical and genetic analysis of a novel CHD4 gene variant in a Chinese patient with Sifrim-Hitz-Weiss syndrome]. 61
33423261 2021
5
Nucleosome-CHD4 chromatin remodeler structure maps human disease mutations. 61
32543371 2020
6
The CHD4-related syndrome: a comprehensive investigation of the clinical spectrum, genotype-phenotype correlations, and molecular basis. 61
31388190 2020

Variations for Sifrim-Hitz-Weiss Syndrome

ClinVar genetic disease variations for Sifrim-Hitz-Weiss Syndrome:

6 (show all 29)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CHD4 NM_001273.5(CHD4):c.3203G>A (p.Arg1068His) SNV Pathogenic 266124 rs886039915 GRCh37: 12:6700879-6700879
GRCh38: 12:6591713-6591713
2 CHD4 NM_001273.5(CHD4):c.3518G>T (p.Arg1173Leu) SNV Pathogenic 266127 rs886039918 GRCh37: 12:6697063-6697063
GRCh38: 12:6587897-6587897
3 CHD4 NM_001273.5(CHD4):c.2552C>A (p.Ser851Tyr) SNV Pathogenic 266125 rs886039916 GRCh37: 12:6702357-6702357
GRCh38: 12:6593191-6593191
4 CHD4 NM_001273.5(CHD4):c.3443G>T (p.Trp1148Leu) SNV Pathogenic 266128 rs886039919 GRCh37: 12:6697486-6697486
GRCh38: 12:6588320-6588320
5 CHD4 NM_001273.5(CHD4):c.3380G>A (p.Arg1127Gln) SNV Pathogenic 266126 rs886039917 GRCh37: 12:6697549-6697549
GRCh38: 12:6588383-6588383
6 CHD2 NM_001271.4(CHD2):c.4280del (p.Pro1427fs) Deletion Pathogenic 984643 GRCh37: 15:93547847-93547847
GRCh38: 15:93004617-93004617
7 CHD4 NM_001273.5(CHD4):c.637A>G (p.Ser213Gly) SNV Likely pathogenic 976740 GRCh37: 12:6710617-6710617
GRCh38: 12:6601451-6601451
8 CHD4 NM_001273.5(CHD4):c.3745T>G (p.Tyr1249Asp) SNV Likely pathogenic 417890 rs1060499583 GRCh37: 12:6696684-6696684
GRCh38: 12:6587518-6587518
9 CHD4 NM_001273.5(CHD4):c.3280G>A (p.Glu1094Lys) SNV Likely pathogenic 975671 GRCh37: 12:6700692-6700692
GRCh38: 12:6591526-6591526
10 CHD4 NM_001273.5(CHD4):c.2189A>G (p.Gln730Arg) SNV Likely pathogenic 977795 GRCh37: 12:6703749-6703749
GRCh38: 12:6594583-6594583
11 CHD4 NM_001273.5(CHD4):c.2366A>T (p.Asn789Ile) SNV Likely pathogenic 983501 GRCh37: 12:6702730-6702730
GRCh38: 12:6593564-6593564
12 CHD4 NM_001273.5(CHD4):c.3409A>C (p.Thr1137Pro) SNV Likely pathogenic 984642 GRCh37: 12:6697520-6697520
GRCh38: 12:6588354-6588354
13 CHD4 NM_001273.5(CHD4):c.3403C>G (p.Leu1135Val) SNV Likely pathogenic 802815 rs1592270989 GRCh37: 12:6697526-6697526
GRCh38: 12:6588360-6588360
14 CHD4 NM_001273.5(CHD4):c.2978A>G (p.Asn993Ser) SNV Likely pathogenic 828192 rs1592273799 GRCh37: 12:6701194-6701194
GRCh38: 12:6592028-6592028
15 CHD4 NM_001273.5(CHD4):c.3517C>T (p.Arg1173Trp) SNV Likely pathogenic 1030325 GRCh37: 12:6697064-6697064
GRCh38: 12:6587898-6587898
16 CHD4 NM_001273.5(CHD4):c.3539T>G (p.Val1180Gly) SNV Likely pathogenic 1030326 GRCh37: 12:6697042-6697042
GRCh38: 12:6587876-6587876
17 CHD4 NM_001273.5(CHD4):c.3548G>A (p.Arg1183His) SNV Likely pathogenic 1030327 GRCh37: 12:6697033-6697033
GRCh38: 12:6587867-6587867
18 CHD4 NM_001273.5(CHD4):c.4822G>A (p.Val1608Ile) SNV Conflicting interpretations of pathogenicity 266123 rs201992075 GRCh37: 12:6690297-6690297
GRCh38: 12:6581131-6581131
19 CHD4 NM_001273.5(CHD4):c.2478T>G (p.Asn826Lys) SNV Uncertain significance 931910 GRCh37: 12:6702618-6702618
GRCh38: 12:6593452-6593452
20 CHD4 NM_001273.5(CHD4):c.4674A>G (p.Pro1558=) SNV Uncertain significance 931924 GRCh37: 12:6690822-6690822
GRCh38: 12:6581656-6581656
21 CHD4 NM_001273.5(CHD4):c.2569A>T (p.Ile857Phe) SNV Uncertain significance 619984 GRCh37: 12:6702340-6702340
GRCh38: 12:6593174-6593174
22 CHD4 NM_001273.5(CHD4):c.5669G>T (p.Arg1890Leu) SNV Uncertain significance 996999 GRCh37: 12:6680087-6680087
GRCh38: 12:6570921-6570921
23 CHD4 NM_001273.5(CHD4):c.3977A>T (p.Gln1326Leu) SNV Uncertain significance 1030328 GRCh37: 12:6692447-6692447
GRCh38: 12:6583281-6583281
24 CHD4 NM_001273.5(CHD4):c.446A>T (p.Lys149Ile) SNV Uncertain significance 1030329 GRCh37: 12:6710925-6710925
GRCh38: 12:6601759-6601759
25 CHD4 NM_001273.5(CHD4):c.4780T>C (p.Cys1594Arg) SNV Uncertain significance 1030330 GRCh37: 12:6690339-6690339
GRCh38: 12:6581173-6581173
26 CHD4 NM_001273.5(CHD4):c.100+11C>G SNV Uncertain significance 1033396 GRCh37: 12:6715429-6715429
GRCh38: 12:6606263-6606263
27 CHD4 NM_001273.5(CHD4):c.239G>A (p.Arg80Gln) SNV Uncertain significance 1033397 GRCh37: 12:6711325-6711325
GRCh38: 12:6602159-6602159
28 CHD4 NM_001273.5(CHD4):c.3308A>C (p.Asn1103Thr) SNV Uncertain significance 1033398 GRCh37: 12:6700664-6700664
GRCh38: 12:6591498-6591498
29 CHD4 NM_001273.5(CHD4):c.4982-11A>G SNV Uncertain significance 1033399 GRCh37: 12:6687723-6687723
GRCh38: 12:6578557-6578557

UniProtKB/Swiss-Prot genetic disease variations for Sifrim-Hitz-Weiss Syndrome:

72
# Symbol AA change Variation ID SNP ID
1 CHD4 p.Ser851Tyr VAR_077146 rs886039916
2 CHD4 p.Gly1003Asp VAR_077147
3 CHD4 p.Arg1068His VAR_077148 rs886039915
4 CHD4 p.Arg1127Gln VAR_077149 rs886039917
5 CHD4 p.Trp1148Leu VAR_077150 rs886039919
6 CHD4 p.Arg1173Leu VAR_077151 rs886039918

Expression for Sifrim-Hitz-Weiss Syndrome

Search GEO for disease gene expression data for Sifrim-Hitz-Weiss Syndrome.

Pathways for Sifrim-Hitz-Weiss Syndrome

Pathways related to Sifrim-Hitz-Weiss Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.03 CHD4 CHD2

GO Terms for Sifrim-Hitz-Weiss Syndrome

Biological processes related to Sifrim-Hitz-Weiss Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin organization GO:0006325 8.96 CHD4 CHD2
2 DNA duplex unwinding GO:0032508 8.62 CHD4 CHD2

Molecular functions related to Sifrim-Hitz-Weiss Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 helicase activity GO:0004386 8.96 CHD4 CHD2
2 DNA helicase activity GO:0003678 8.62 CHD4 CHD2

Sources for Sifrim-Hitz-Weiss 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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