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SCS
MCID: STH001
MIFTS: 66

Saethre-Chotzen Syndrome (SCS)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Saethre-Chotzen Syndrome

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MalaCards integrated aliases for Saethre-Chotzen Syndrome:

Name: Saethre-Chotzen Syndrome 57 12 74 25 20 43 58 73 36 29 54 6 15 71
Acs3 57 20 43 58 73
Scs 57 20 43 58 73
Acrocephaly, Skull Asymmetry, and Mild Syndactyly 57 20 43
Acrocephalosyndactyly Type 3 20 58 73
Chotzen Syndrome 57 20 43
Acs Iii 57 43 73
Acrocephalosyndactyly, Type Iii 57 43
Acrocephalosyndactyly Type Iii 12 25
Saethre-Chotzen Syndrome with or Without Eyelid Anomalies 57
Syndrome, Saethre-Chotzen, with/without Eyelid Anomalies 39
Dysostosis Craniofacialis with Hypertelorism 43
Acrocephalosyndactyly, Type Iii; Acs3 57
Acrocephalo-Syndactyly, Type 3 20
Acrocephalosyndactyly Iii 43
Sakati Syndrome 71
Acs 3 20

Characteristics:

Orphanet epidemiological data:

58
saethre-chotzen syndrome
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Europe); Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM®:

57 (Updated 05-Mar-2021)
Miscellaneous:
variable expressivity
few patients with mild to moderate mental retardation
incidence of 1 in 25,000 to 1 in 50,000 newborns
phenotypic overlap with muenke syndrome due to a mutation in the fgfr3 gene (p250r, )

Inheritance:
autosomal dominant


HPO:

31
saethre-chotzen syndrome:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity


GeneReviews:

25
Penetrance Precise penetrance data are not available; however, wide phenotypic variability and incomplete penetrance are well described [dollfus et al 2002, de heer et al 2005].

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Eye diseases Bone diseases
See all MalaCards categories (disease lists)
ICD10: 33
Orphanet: 58  
Rare eye diseases
Rare bone diseases
Developmental anomalies during embryogenesis


Sources

Summaries for Saethre-Chotzen Syndrome

About this section
MedlinePlus Genetics : 43 Saethre-Chotzen syndrome is a genetic condition characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.Most people with Saethre-Chotzen syndrome have prematurely fused skull bones along the coronal suture, the growth line that goes over the head from ear to ear. Other parts of the skull may be malformed as well. These changes can result in an abnormally shaped head, a high forehead, a low frontal hairline, droopy eyelids (ptosis), widely spaced eyes, and a broad nasal bridge. One side of the face may appear noticeably different from the other (facial asymmetry). Most people with Saethre-Chotzen syndrome also have small, rounded ears.The signs and symptoms of Saethre-Chotzen syndrome vary widely, even among affected individuals in the same family. This condition can cause mild changes in the hands and feet, such as partial fusion of the skin between the second and third fingers on each hand and a broad or duplicated first (big) toe. Delayed development and learning difficulties have been reported, although most people with this condition are of normal intelligence. Less common signs and symptoms of Saethre-Chotzen syndrome include short stature, abnormalities of the bones of the spine (the vertebra), hearing loss, and heart defects.Robinow-Sorauf syndrome is a condition with features similar to those of Saethre-Chotzen syndrome, including craniosynostosis and broad or duplicated great toes. It was once considered a separate disorder, but was found to result from mutations in the same gene and is now thought to be a variant of Saethre-Chotzen syndrome.

MalaCards based summary : Saethre-Chotzen Syndrome, also known as acs3, is related to chromosome 2q35 duplication syndrome and craniosynostosis. An important gene associated with Saethre-Chotzen Syndrome is TWIST1 (Twist Family BHLH Transcription Factor 1), and among its related pathways/superpathways are VEGF Signaling and Development FGFR signaling pathway. The drugs Triamcinolone and Cyclophosphamide have been mentioned in the context of this disorder. Affiliated tissues include skull, eye and heart, and related phenotypes are clinodactyly of the 5th finger and facial asymmetry

Disease Ontology : 12 An acrocephalosyndactylia that has material basis in a genetic mutation in the TWIST1 gene which results in premature fusion located in skull.

GARD : 20 Saethre-Chotzen syndrome is a genetic condition characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape and symmetry of the head and face. Other features may include webbing of certain fingers or toes (syndactyly), small or unusually shaped ears, short stature, and abnormalities of the bones in the spine (the vertebrae). The signs and symptoms of Saethre-Chotzen syndrome vary widely, even among affected individuals in the same family. Mutations (variants) in the TWIST1 gene cause most cases of Saethre-Chotzen syndrome. The condition is inherited in an autosomal dominant pattern. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. Treatment is aimed at addressing the symptoms found in each individual and may require the coordinated efforts of a team of specialists. Surgery is often needed to prevent or correct early closure of the cranial sutures and correct certain craniofacial abnormalities, syndactyly and/or skeletal defects.

OMIM® : 57 Saethre-Chotzen syndrome is characterized by craniosynostosis, facial dysmorphism, and hand and foot abnormalities. Coronal synostosis resulting in brachycephaly is the most frequent cranial abnormality observed, and the most common facial features are asymmetry, hypertelorism, and maxillary hypoplasia. Other features include high forehead, low frontal hairline, late-closing fontanel, strabismus, ptosis, lacrimal duct stenosis, deviated nasal septum, small low-set posteriorly rotated ears with prominent crus, and hearing loss. The limb anomalies consist of radioulnar synostosis, brachydactyly, cutaneous syndactyly, and hallux valgus. Patients also exhibit short stature and vertebral fusion, and mild to moderate mental retardation has been noted in some cases. Inter- and intrafamilial variability is significant, with some patients having fusion of other sutures, or no apparent craniosynostosis but abnormal skull morphology. The degree of syndactyly is also variable, and digital abnormalities can be absent (Jabs, 2008). (101400) (Updated 05-Mar-2021)

KEGG : 36 Saethre-Chotzen syndrome (SCS) is an autosomal dominant disease characterized by craniosynostosis, ptosis, and limb and external ear abnormalities. Mutations in the TWIST gene have been extensively reported in SCS. In addition, mutations in FGFR2 was also detected.

UniProtKB/Swiss-Prot : 73 Saethre-Chotzen syndrome: A craniosynostosis syndrome characterized by coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, hypertelorism, broad halluces, and clinodactyly.

Wikipedia : 74 Saethre-Chotzen syndrome (SCS), also known as acrocephalosyndactyly type III, is a rare congenital... more...

GeneReviews: NBK1189
Sources

Related Diseases for Saethre-Chotzen Syndrome

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Diseases related to Saethre-Chotzen Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 169)
# Related Disease Score Top Affiliating Genes
1 chromosome 2q35 duplication syndrome 32.3 TWIST1 MSX2 HAND2 FGFR3 FGFR2 FGFR1
2 craniosynostosis 31.6 TWIST1 RUNX2 RECQL4 MSX2 FGFR3 FGFR2
3 parietal foramina 31.2 TWIST1 RUNX2 RECQL4 MSX2 FGFR3
4 synostosis 31.2 TWIST1 RUNX2 RECQL4 MSX2 FGFR3 FGFR2
5 muenke syndrome 31.1 TWIST1 MSX2 FGFR3 FGFR2 FGFR1
6 syndromic craniosynostosis 31.1 TWIST1 RUNX2 MSX2 FGFR3 FGFR2 FGFR1
7 brachydactyly 31.1 RUNX2 MSX2 FGFR3 COL1A2
8 strabismus 31.0 TWIST1 FGFR3 FGFR2 COL1A2
9 jackson-weiss syndrome 30.9 MSX2 FGFR3 FGFR2 FGFR1
10 crouzon syndrome 30.9 TWIST1 RUNX2 MSX2 FGFR3 FGFR2 FGFR1
11 craniosynostosis 1 30.8 TWIST1 FGFR3 FGFR2
12 radioulnar synostosis 30.7 TWIST1 RECQL4 FGFR3 FGFR2 FGFR1
13 cleft palate, isolated 30.6 TWIST1 RUNX2 MSX2 IBSP FGFR3 FGFR2
14 pfeiffer syndrome 30.6 TWIST1 RUNX2 MSX2 FGFR3 FGFR2 FGFR1
15 ankylosis 30.6 RUNX2 IBSP FGFR2 FGFR1 BGLAP
16 scoliosis 30.6 RUNX2 FGFR3 FGFR2 COL1A2 BGLAP
17 apert syndrome 30.3 TWIST2 TWIST1 RUNX2 MSX2 HAND2 FGFR3
18 baller-gerold syndrome 11.4
19 robinow-sorauf syndrome 11.3
20 fontaine progeroid syndrome 11.3
21 sucla2-related mitochondrial dna depletion syndrome, encephalomyopathic form with methylmalonic aciduria 10.9
22 ptosis 10.8
23 helix syndrome 10.6
24 intracranial hypertension 10.5
25 hemifacial hyperplasia 10.5 FGFR3 FGFR2
26 hypertelorism 10.5
27 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.5
28 partial trisomy distal 4q 10.4 TWIST2 HAND2
29 testicular spermatocytic seminoma 10.4 FGFR3 FGFR2
30 dacryocystocele 10.4 FGFR3 FGFR2
31 chronic inflammation of lacrimal passage 10.4 FGFR3 FGFR2
32 fgfr craniosynostosis syndromes 10.4 FGFR3 FGFR2 FGFR1
33 parietal foramina with cleidocranial dysplasia 10.4 RUNX2 MSX2
34 achondroplasia, severe, with developmental delay and acanthosis nigricans 10.4 FGFR3 FGFR2 FGFR1
35 synovial chondromatosis 10.4 RUNX2 FGFR3 FGFR1
36 deafness, autosomal recessive 71 10.4 FGFR3 FGFR2 FGFR1
37 luteoma 10.4 FGFR3 FGFR2
38 sweeney-cox syndrome 10.4 TWIST2 TWIST1 CFAP47
39 osteoglophonic dysplasia 10.4 FGFR3 FGFR2 FGFR1
40 hypochondroplasia 10.4 FGFR3 FGFR2 FGFR1
41 lacrimoauriculodentodigital syndrome 10.4 FGFR3 FGFR2 FGFR1
42 dental pulp disease 10.4 RUNX2 IBSP BGLAP
43 antley-bixler syndrome 10.4 FGFR3 FGFR2 FGFR1
44 tooth resorption 10.4 RUNX2 IBSP BGLAP
45 nevus, epidermal 10.4 FGFR3 FGFR2 FGFR1
46 plagiocephaly 10.4 TWIST1 FGFR3 FGFR2 FGFR1
47 bladder transitional cell papilloma 10.4 FGFR3 CASP2
48 ischemic bone disease 10.4 RUNX2 IBSP BGLAP
49 split hand-foot malformation 10.4 HAND2 FGFR2 FGFR1
50 hypophosphatasia 10.4 RUNX2 BGLAP ALPP

Graphical network of the top 20 diseases related to Saethre-Chotzen Syndrome:



Diseases related to Saethre-Chotzen Syndrome
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Symptoms & Phenotypes for Saethre-Chotzen Syndrome

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Human phenotypes related to Saethre-Chotzen Syndrome:

58 31 (show top 50) (show all 77)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 clinodactyly of the 5th finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0004209
2 facial asymmetry 58 31 hallmark (90%) Very frequent (99-80%) HP:0000324
3 high forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0000348
4 craniosynostosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001363
5 finger syndactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0006101
6 ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0000508
7 hyperlordosis 58 31 frequent (33%) Frequent (79-30%) HP:0003307
8 depressed nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0005280
9 narrow palate 58 31 frequent (33%) Frequent (79-30%) HP:0000189
10 hypertelorism 58 31 frequent (33%) Frequent (79-30%) HP:0000316
11 open bite 58 31 frequent (33%) Frequent (79-30%) HP:0010807
12 microtia 58 31 frequent (33%) Frequent (79-30%) HP:0008551
13 brachycephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000248
14 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
15 external ear malformation 58 31 frequent (33%) Frequent (79-30%) HP:0008572
16 brachydactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001156
17 bilateral single transverse palmar creases 58 31 frequent (33%) Frequent (79-30%) HP:0007598
18 low anterior hairline 58 31 frequent (33%) Frequent (79-30%) HP:0000294
19 prominent nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0000426
20 convex nasal ridge 58 31 frequent (33%) Frequent (79-30%) HP:0000444
21 blepharospasm 58 31 frequent (33%) Frequent (79-30%) HP:0000643
22 narrow internal auditory canal 58 31 frequent (33%) Frequent (79-30%) HP:0011386
23 delayed cranial suture closure 58 31 frequent (33%) Frequent (79-30%) HP:0000270
24 plagiocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0001357
25 abnormality of the antihelix 58 31 frequent (33%) Frequent (79-30%) HP:0009738
26 prominent crus of helix 58 31 frequent (33%) Frequent (79-30%) HP:0009899
27 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
28 sleep apnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0010535
29 increased intracranial pressure 58 31 occasional (7.5%) Occasional (29-5%) HP:0002516
30 sensorineural hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000407
31 optic atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000648
32 short stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0004322
33 broad thumb 58 31 occasional (7.5%) Occasional (29-5%) HP:0011304
34 abnormal form of the vertebral bodies 58 31 occasional (7.5%) Occasional (29-5%) HP:0003312
35 cleft palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000175
36 cryptorchidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000028
37 low-set ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000369
38 epicanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000286
39 hypoplasia of the maxilla 58 31 occasional (7.5%) Occasional (29-5%) HP:0000327
40 conductive hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000405
41 amblyopia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000646
42 intellectual disability, moderate 58 31 occasional (7.5%) Occasional (29-5%) HP:0002342
43 hallux valgus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001822
44 migraine 58 31 occasional (7.5%) Occasional (29-5%) HP:0002076
45 hypotelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000601
46 triphalangeal thumb 58 31 occasional (7.5%) Occasional (29-5%) HP:0001199
47 proximal radio-ulnar synostosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0005037
48 intellectual disability 31 occasional (7.5%) HP:0001249
49 abnormality of cardiovascular system morphology 31 occasional (7.5%) HP:0030680
50 seizure 31 occasional (7.5%) HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Head And Neck Eyes:
ptosis
hypertelorism
strabismus
buphthalmos
shallow orbits
more
Growth Height:
short stature

Head And Neck Face:
flat face
facial asymmetry
maxillary hypoplasia
high, flat forehead
low frontal hairline

Skeletal Hands:
brachydactyly
syndactyly, mild (often 2nd-3rd fingers)
bifid terminal phalanges (digits 2 and 3)
fifth finger clinodactyly

Skeletal Limbs:
radioulnar synostosis

Head And Neck Nose:
thin, long, pointed nose
beaked nose

Cardiovascular Vascular:
intracranial hypertension due to multisutural cranial fusion

Neoplasia:
increased risk of breast cancer in women

Head And Neck Mouth:
narrow palate
cleft palate

Head And Neck Head:
brachycephaly
acrocephaly

Head And Neck Ears:
low-set ears
long and prominent ear crus
small ears
apical cartilage deformity
deafness

Skeletal Feet:
hallux valgus
absent first metatarsal
syndactyly (often 3rd-4th toes)

Skeletal Skull:
parietal foramina
acrocephaly
late closing fontanelles
craniosynostosis of coronal, lambdoid, and/or metopic sutures

Cardiovascular Heart:
congenital heart defect

Skeletal Pelvis:
small ilia
large ischia

Clinical features from OMIM®:

101400 (Updated 05-Mar-2021)

GenomeRNAi Phenotypes related to Saethre-Chotzen Syndrome according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 shRNA abundance <= 50% GR00343-S 9.1 ACSL3 BGLAP FGFR3 RUNX2 TCF3 TWIST1

MGI Mouse Phenotypes related to Saethre-Chotzen Syndrome:

46 (show all 17)
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.44 BGLAP CASP2 CBL COL1A2 CRPPA FERD3L
2 growth/size/body region MP:0005378 10.37 ACSL3 CBL COL1A2 FGFR1 FGFR2 FGFR3
3 hematopoietic system MP:0005397 10.37 ACSL3 BGLAP CASP2 CBL COL1A2 FGFR1
4 immune system MP:0005387 10.35 ACSL3 BGLAP CASP2 CBL COL1A2 FGFR1
5 craniofacial MP:0005382 10.3 CBL FGFR1 FGFR2 FGFR3 HAND2 IBSP
6 endocrine/exocrine gland MP:0005379 10.28 BGLAP CASP2 CBL FGFR1 FGFR2 HAND2
7 digestive/alimentary MP:0005381 10.25 FGFR1 FGFR2 FGFR3 HAND2 IBSP MSX2
8 limbs/digits/tail MP:0005371 10.25 CBL COL1A2 FGFR1 FGFR2 FGFR3 HAND2
9 mortality/aging MP:0010768 10.25 CASP2 CBL COL1A2 CRPPA FGFR1 FGFR2
10 nervous system MP:0003631 10.13 CASP2 COL1A2 CRPPA FERD3L FGFR1 FGFR2
11 integument MP:0010771 10.11 CBL COL1A2 FGFR1 FGFR2 FGFR3 MSX2
12 hearing/vestibular/ear MP:0005377 10.05 CBL FGFR1 FGFR2 FGFR3 HAND2 MSX2
13 muscle MP:0005369 10.02 CBL COL1A2 FGFR1 FGFR2 HAND2 MSX2
14 no phenotypic analysis MP:0003012 9.8 CRPPA FGFR1 FGFR2 FGFR3 HAND2 RUNX2
15 normal MP:0002873 9.76 COL1A2 FGFR1 FGFR2 FGFR3 HAND2 MSX2
16 reproductive system MP:0005389 9.61 BGLAP CASP2 CBL FGFR1 FGFR2 FGFR3
17 skeleton MP:0005390 9.44 BGLAP CBL COL1A2 FGFR1 FGFR2 FGFR3
Sources

Drugs & Therapeutics for Saethre-Chotzen Syndrome

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Drugs for Saethre-Chotzen Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Triamcinolone Approved, Vet_approved Phase 3 124-94-7 31307
2
Cyclophosphamide Approved, Investigational Phase 3 50-18-0, 6055-19-2 2907
3
Goserelin Approved Phase 3 65807-02-5 47725 5311128
4 Immunosuppressive Agents Phase 3
5 taxane Phase 3
6 Hormones Phase 3
7 Triamcinolone hexacetonide Phase 3
8 triamcinolone acetonide Phase 3
9 Immunologic Factors Phase 3
10 Triamcinolone diacetate Phase 3
11 Antirheumatic Agents Phase 3
12 Antineoplastic Agents, Hormonal Phase 3
13 Alkylating Agents Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Administration During Chemotherapy to Reduce Ovarian Failure Following Chemotherapy in Early Stage, Hormone-Receptor Negative Breast Cancer Completed NCT01530607 Phase 3 Standard cyclophosphamide;Goserelin (Zoladex)
2 Validation of "Montreal Cognitive Assessment (MoCA) and Addenbrooke's Cognitive Examination III (ACE-III) "as a Cognitive Screening Tools for the Hearing Impaired Terminated NCT03648502

Search NIH Clinical Center for Saethre-Chotzen Syndrome

Sources

Genetic Tests for Saethre-Chotzen Syndrome

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Genetic tests related to Saethre-Chotzen Syndrome:

# Genetic test Affiliating Genes
1 Saethre-Chotzen Syndrome 29 FGFR2 TWIST1
Sources

Anatomical Context for Saethre-Chotzen Syndrome

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The Foundational Model of Anatomy Ontology organs/tissues related to Saethre-Chotzen Syndrome:

19
Skull

MalaCards organs/tissues related to Saethre-Chotzen Syndrome:

40
Eye, Heart, Breast, Bone, Brain, Spinal Cord, Ovary
Sources

Publications for Saethre-Chotzen Syndrome

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Articles related to Saethre-Chotzen Syndrome:

(show top 50) (show all 318)
# Title Authors PMID Year
1
Genetic heterogeneity of Saethre-Chotzen syndrome, due to TWIST and FGFR mutations. 61 54 6 57 25
9585583 1998
2
Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome. 61 6 25 54 57
8988166 1997
3
Saethre-Chotzen syndrome: notable intrafamilial phenotypic variability in a large family with Q28X TWIST mutation. 6 25 61 57
11977182 2002
4
Another TWIST on Baller-Gerold syndrome. 6 25 54 61
11754069 2001
5
Mutations of the TWIST gene in the Saethre-Chotzen syndrome. 25 57 61 54
8988167 1997
6
Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome. 57 25 61
16251895 2006
7
TWIST gene mutation in a patient with radial aplasia and craniosynostosis: further evidence for heterogeneity of Baller-Gerold syndrome. 61 25 6
9934984 1999
8
Linkage of blepharophimosis syndrome in a large Indian pedigree to chromosome 7p. 57 6
8968762 1996
9
Mutations in the basic domain and the loop-helix II junction of TWIST abolish DNA binding in Saethre-Chotzen syndrome. 6 54 61
11248247 2001
10
Mutations within or upstream of the basic helix-loop-helix domain of the TWIST gene are specific to Saethre-Chotzen syndrome. 6 61 54
10094188 1999
11
A comprehensive screen for TWIST mutations in patients with craniosynostosis identifies a new microdeletion syndrome of chromosome band 7p21.1. 54 57 61
9792856 1998
12
The TWIST gene, although not disrupted in Saethre-Chotzen patients with apparently balanced translocations of 7p21, is mutated in familial and sporadic cases. 61 54 6
9259286 1997
13
A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome. 6 25
9042914 1997
14
Saethre-Chotzen syndrome: a case report. 25 61 54
19860490 2010
15
Cytogenetic and molecular characterization of a de-novo cryptic deletion of 7p21 associated with an apparently balanced translocation and complex craniosynostosis. 25 54 61
17786117 2007
16
Women with Saethre-Chotzen syndrome are at increased risk of breast cancer. 61 57
17437280 2007
17
Clinical and genetic analysis of patients with Saethre-Chotzen syndrome. 61 25 54
15923834 2005
18
Deletion of the TWIST gene in a large five-generation family. 61 54 25
15099347 2004
19
Increased risk for developmental delay in Saethre-Chotzen syndrome is associated with TWIST deletions: an improved strategy for TWIST mutation screening. 54 61 25
14513358 2003
20
A novel mutation in the TWIST gene, implicated in Saethre-Chotzen syndrome, is found in the original case of Robinow-Sorauf syndrome. 25 54 61
12791045 2003
21
Genetic analysis of patients with the Saethre-Chotzen phenotype. 57 61
12116251 2002
22
A child with Saethre-Chotzen syndrome, sensorineural hearing loss, and a TWIST mutation. 61 25 54
11772178 2002
23
A new twist: some patients with Saethre-Chotzen syndrome have a microdeletion syndrome. 57 61
9792855 1998
24
The variable expressivity and incomplete penetrance of the twist-null heterozygous mouse phenotype resemble those of human Saethre-Chotzen syndrome. 61 25 54
9580658 1998
25
Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family. 61 6
9279764 1997
26
Possible genetic heterogeneity in the Saethre-Chotzen syndrome. 57 61
8698349 1996
27
Craniosynostosis suggestive of Saethre-Chotzen syndrome: clinical description of a large kindred and exclusion of candidate regions on 7p. 61 6
8723106 1996
28
Saethre-Chotzen syndrome associated with balanced translocations involving 7p21: three further families. 61 57
7783164 1995
29
Evidence that the Saethre-Chotzen syndrome locus lies between D7S664 and D7S507, by genetic analysis and detection of a microdeletion in a patient. 61 57
7977380 1994
30
Localization of the genetic locus for Saethre-Chotzen syndrome to a 6 cM region of chromosome 7 using four cases with apparently balanced translocations at 7p21.2. 61 57
7987323 1994
31
Saethre-Chotzen syndrome. 57 61
8064818 1994
32
Genetic heterogeneity among craniosynostosis syndromes: mapping the Saethre-Chotzen syndrome locus between D7S513 and D7S516 and exclusion of Jackson-Weiss and Crouzon syndrome loci from 7p. 57 61
8188211 1994
33
Saethre-Chotzen syndrome with familial translocation at chromosome 7p22. 61 57
8266989 1993
34
The mapping of a gene for craniosynostosis: evidence for linkage of the Saethre-Chotzen syndrome to distal chromosome 7p. 61 57
1433226 1992
35
Saethre-Chotzen syndrome (ACS III) in four generations. 57 61
1756600 1991
36
Auralcephalosyndactyly: a new craniosynostosis syndrome or a variant of the Saethre-Chotzen syndrome? 61 57
2769726 1989
37
A family with the Saethre-Chotzen syndrome. 57 61
4073118 1985
38
The Saethre-Chotzen syndrome with partial bifid of the distal phalanges of the great toes. Observations of three cases in one family. 57 61
7450776 1980
39
Unusual association of Saethre-Chotzen syndrome and congenital adrenal hyperplasia. 57 61
862213 1977
40
The Saethre-Chotzen syndrome. 61 57
4643612 1972
41
New Pattern of Sutural Synostosis Associated With TWIST Gene Mutation and Saethre-Chotzen Syndrome: Peace Sign Synostosis. 61 25
26114524 2015
42
Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants. 61 25
25271085 2015
43
Severe Developmental Delay in a Patient with 7p21.1-p14.3 Microdeletion Spanning the TWIST Gene and the HOXA Gene Cluster. 61 25
22570644 2011
44
Pivotal role of Twist in skeletal biology and pathology. 61 25
20696219 2010
45
Long-term functional outcome in 167 patients with syndromic craniosynostosis; defining a syndrome-specific risk profile. 25 61
19913472 2010
46
The natural history of patients treated for TWIST1-confirmed Saethre-Chotzen syndrome. 61 25
19952666 2009
47
The frequency of palatal anomalies in Saethre-Chotzen syndrome. 25 61
19642760 2009
48
Clinical and molecular diagnosis of the skeletal dysplasias associated with mutations in the gene encoding Fibroblast Growth Factor Receptor 3 (FGFR3) in Portugal. 6
19215249 2009
49
Twist1 homodimers enhance FGF responsiveness of the cranial sutures and promote suture closure. 25 61
18471809 2008
50
Saethre-Chotzen syndrome with severe developmental delay associated with deletion of chromosomic region 7p15 --> pter. 61 25
18019370 2007
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Variations for Saethre-Chotzen Syndrome

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ClinVar genetic disease variations for Saethre-Chotzen Syndrome:

6 (show top 50) (show all 174)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FGFR2 NM_000141.5(FGFR2):c.1150G>A (p.Gly384Arg) SNV Pathogenic 478046 rs1554927408 10:123274768-123274768 10:121515254-121515254
2 FGFR2 NM_000141.5(FGFR2):c.1124A>G (p.Tyr375Cys) SNV Pathogenic 13277 rs121913478 10:123274794-123274794 10:121515280-121515280
3 FGFR2 NM_000141.5(FGFR2):c.1025G>A (p.Cys342Tyr) SNV Pathogenic 13263 rs121918487 10:123276892-123276892 10:121517378-121517378
4 TWIST1 NM_000474.4(TWIST1):c.82C>T (p.Gln28Ter) SNV Pathogenic 7983 rs104894055 7:19156863-19156863 7:19117240-19117240
5 FGFR2 NM_000141.5(FGFR2):c.804_809del (p.Val269_Val270del) Deletion Pathogenic 13285 rs879253718 10:123279623-123279628 10:121520109-121520114
6 FGFR2 NM_000141.5(FGFR2):c.755C>G (p.Ser252Trp) SNV Pathogenic 13272 rs79184941 10:123279677-123279677 10:121520163-121520163
7 FGFR3 NM_000142.5(FGFR3):c.749C>G (p.Pro250Arg) SNV Pathogenic 16340 rs4647924 4:1803571-1803571 4:1801844-1801844
8 FGFR2 NM_000141.5(FGFR2):c.1032G>A (p.Ala344=) SNV Pathogenic 13268 rs121918491 10:123276885-123276885 10:121517371-121517371
9 FGFR2 NM_000141.5(FGFR2):c.758C>G (p.Pro253Arg) SNV Pathogenic 13273 rs77543610 10:123279674-123279674 10:121520160-121520160
10 TWIST1 NM_000474.4(TWIST1):c.321dup (p.Thr108fs) Duplication Pathogenic 973874 7:19156623-19156624 7:19117000-19117001
11 TWIST1 NM_000474.4(TWIST1):c.433A>G (p.Lys145Glu) SNV Pathogenic 970861 7:19156512-19156512 7:19116889-19116889
12 TWIST1 NM_000474.4(TWIST1):c.306_307del (p.Tyr103fs) Deletion Pathogenic 691563 rs1585617240 7:19156638-19156639 7:19117015-19117016
13 TWIST1 NM_000474.4(TWIST1):c.376G>T (p.Glu126Ter) SNV Pathogenic 7977 rs121909188 7:19156569-19156569 7:19116946-19116946
14 TWIST1 NM_000474.4(TWIST1):c.398_418dup (p.Ser140Ter) Duplication Pathogenic 567420 rs1563159980 7:19156526-19156527 7:19116903-19116904
15 TWIST1 NM_000474.4(TWIST1):c.132_142del (p.Ser45fs) Deletion Pathogenic 543077 rs1554442082 7:19156803-19156813 7:19117180-19117190
16 TWIST1 NM_000474.4(TWIST1):c.408dup (p.Thr137fs) Duplication Pathogenic 543076 rs1554441993 7:19156536-19156537 7:19116913-19116914
17 TWIST1 NM_000474.4(TWIST1):c.396_416dup (p.Lys133_Pro139dup) Duplication Pathogenic 543075 rs1554441991 7:19156528-19156529 7:19116905-19116906
18 FGFR2 NM_022970.3(FGFR2):c.314A>G (p.Tyr105Cys) SNV Pathogenic 449024 rs1434545235 10:123325014-123325014 10:121565500-121565500
19 TWIST1 NC_000007.14:g.(?_19116693)_(19117341_?)del Deletion Pathogenic 458685 7:19116693-19117341
20 CRPPA GRCh37/hg19 7p21.2-21.1(chr7:14470668-20385165)x1 copy number loss Pathogenic 981203 7:14470668-20385165
21 TWIST1 NM_000474.4(TWIST1):c.446T>G (p.Leu149Arg) SNV Pathogenic 835124 7:19156499-19156499 7:19116876-19116876
22 TWIST1 NM_000474.4(TWIST1):c.309C>G (p.Tyr103Ter) SNV Pathogenic 802300 rs104894054 7:19156636-19156636 7:19117013-19117013
23 TWIST1 NM_000474.4(TWIST1):c.211C>T (p.Gln71Ter) SNV Pathogenic 7984 rs104894065 7:19156734-19156734 7:19117111-19117111
24 TWIST1 NM_000474.4(TWIST1):c.397A>T (p.Lys133Ter) SNV Pathogenic 827827 rs1585617015 7:19156548-19156548 7:19116925-19116925
25 TWIST1 NM_000474.4(TWIST1):c.358C>T (p.Arg120Cys) SNV Pathogenic 652940 rs1233220987 7:19156587-19156587 7:19116964-19116964
26 TWIST1 NM_000474.4(TWIST1):c.277dup (p.Ser93fs) Duplication Pathogenic 648741 rs1585617402 7:19156667-19156668 7:19117044-19117045
27 TWIST1 NM_000474.4(TWIST1):c.197del (p.Pro66fs) Deletion Pathogenic 645450 rs1585617611 7:19156748-19156748 7:19117125-19117125
28 TWIST1 NM_000474.4(TWIST1):c.68_75dup (p.Arg26fs) Duplication Pathogenic 642695 rs1585617865 7:19156869-19156870 7:19117246-19117247
29 TWIST1 NM_000474.4(TWIST1):c.301C>T (p.Gln101Ter) SNV Pathogenic 575739 rs1563160116 7:19156644-19156644 7:19117021-19117021
30 TWIST1 NM_000474.4(TWIST1):c.90_111del (p.Lys33fs) Deletion Pathogenic 573378 rs1563160337 7:19156834-19156855 7:19117211-19117232
31 TWIST1 NM_000474.4(TWIST1):c.397_417dup (p.Lys133_Pro139dup) Duplication Pathogenic 458686 rs1554441989 7:19156527-19156528 7:19116904-19116905
32 TWIST1 NM_000474.4(TWIST1):c.395G>C (p.Arg132Pro) SNV Pathogenic 476634 rs1554441995 7:19156550-19156550 7:19116927-19116927
33 TWIST1 NM_000474.4(TWIST1):c.466A>G (p.Ile156Val) SNV Pathogenic 7982 rs104894059 7:19156479-19156479 7:19116856-19116856
34 TWIST1 NM_000474.4(TWIST1):c.541G>T (p.Glu181Ter) SNV Pathogenic 7980 rs104894058 7:19156404-19156404 7:19116781-19116781
35 TWIST1 TWIST1, 21-BP DUP Duplication Pathogenic 7979
36 TWIST1 NM_000474.4(TWIST1):c.392T>C (p.Leu131Pro) SNV Pathogenic 7978 rs121909189 7:19156553-19156553 7:19116930-19116930
37 TWIST1 NM_000474.4(TWIST1):c.376G>T (p.Glu126Ter) SNV Pathogenic 7977 rs121909188 7:19156569-19156569 7:19116946-19116946
38 TWIST1 NM_000474.4(TWIST1):c.368C>A (p.Ser123Ter) SNV Pathogenic 7976 rs121909187 7:19156577-19156577 7:19116954-19116954
39 TWIST1 NM_000474.4(TWIST1):c.309C>A (p.Tyr103Ter) SNV Pathogenic 7975 rs104894054 7:19156636-19156636 7:19117013-19117013
40 TWIST1 NM_000474.4(TWIST1):c.356A>C (p.Gln119Pro) SNV Pathogenic 7974 rs104894057 7:19156589-19156589 7:19116966-19116966
41 TWIST1 NM_000474.4(TWIST1):c.308dup (p.Tyr103Ter) Duplication Pathogenic 7973 rs121909186 7:19156636-19156637 7:19117013-19117014
42 TWIST1 NM_000474.4(TWIST1):c.329G>C (p.Arg110Pro) SNV Likely pathogenic 426307 rs1085307555 7:19156616-19156616 7:19116993-19116993
43 TWIST1 NM_000474.4(TWIST1):c.443C>T (p.Thr148Ile) SNV Likely pathogenic 942829 7:19156502-19156502 7:19116879-19116879
44 TWIST1 NM_000474.4(TWIST1):c.385_405dup (p.Ala129_Ile135dup) Duplication Likely pathogenic 931885 7:19156539-19156540 7:19116916-19116917
45 TWIST1 NM_000474.4(TWIST1):c.171del (p.Gly59fs) Deletion Likely pathogenic 981190 7:19156774-19156774 7:19117151-19117151
46 TWIST1 NM_000474.4(TWIST1):c.329G>C (p.Arg110Pro) SNV Likely pathogenic 426307 rs1085307555 7:19156616-19156616 7:19116993-19116993
47 TWIST1 NM_000474.4(TWIST1):c.475C>G (p.Leu159Val) SNV Likely pathogenic 981189 7:19156470-19156470 7:19116847-19116847
48 TWIST1 NM_000474.4(TWIST1):c.346C>G (p.Arg116Gly) SNV Likely pathogenic 543078 rs1554442019 7:19156599-19156599 7:19116976-19116976
49 TWIST1 NM_000474.4(TWIST1):c.352C>G (p.Arg118Gly) SNV Likely pathogenic 438352 rs1554442015 7:19156593-19156593 7:19116970-19116970
50 TWIST1 NM_000474.4(TWIST1):c.400_420dup (p.Ile134_Ser140dup) Duplication Likely pathogenic 694504 rs1585616948 7:19156524-19156525 7:19116901-19116902

UniProtKB/Swiss-Prot genetic disease variations for Saethre-Chotzen Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 TWIST1 p.Gln119Pro VAR_004495 rs104894057
2 TWIST1 p.Leu131Pro VAR_004496 rs121909189
3 TWIST1 p.Ile156Val VAR_015219 rs104894059

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Expression for Saethre-Chotzen Syndrome

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Search GEO for disease gene expression data for Saethre-Chotzen Syndrome.
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Pathways for Saethre-Chotzen Syndrome

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Pathways related to Saethre-Chotzen Syndrome according to GeneCards Suite gene sharing:

(show all 21)
# Super pathways Score Top Affiliating Genes
1
VEGF Signaling 66
Show member pathways
 12.27 FGFR3 FGFR2 FGFR1 CBL CASP2
2
Development FGFR signaling pathway 23
Show member pathways
 12.25 FGFR3 FGFR2 FGFR1 CBL
3
Signaling by FGFR2 65
Show member pathways
 12.11 FGFR3 FGFR2 FGFR1 CBL
4
Proteoglycans in cancer 36
12.03 TWIST2 TWIST1 FGFR1 COL1A2 CBL
5
Tyrosine Kinases / Adaptors 4
11.93 FGFR3 FGFR2 FGFR1 CBL
6
Signaling pathways regulating pluripotency of stem cells 36
11.89 TCF3 FGFR3 FGFR2 FGFR1
7
Parathyroid hormone synthesis, secretion and action 36
11.79 RUNX2 FGFR1 BGLAP
8
Angiogenesis (CST) 4
11.7 FGFR3 FGFR2 FGFR1
9
Mesenchymal Stem Cell Differentiation Pathways and Lineage-specific Markers 64
11.65 RUNX2 MSX2 BGLAP ALPP
10
Regulation of nuclear SMAD2/3 signaling 1
11.63 TCF3 RUNX2 COL1A2
11
G-protein signaling_RhoA regulation pathway 23
11.59 FGFR3 FGFR2 FGFR1 CBL
12
Central carbon metabolism in cancer 36
11.58 FGFR3 FGFR2 FGFR1
13
Endochondral Ossification 1
11.54 RUNX2 FGFR3 FGFR1
14
Neural Crest Differentiation 1
11.36 TWIST1 MSX2 FGFR3 FGFR2 FGFR1
15
Alzheimers Disease Pathway 63
11.34 FGFR3 FGFR2 FGFR1
16
Interleukin-11 Signaling Pathway 1
11.31 RUNX2 IBSP BGLAP
17
Vemurafenib Pathway, Pharmacodynamics 60
11.29 FGFR3 FGFR2 FGFR1
18
Notch-mediated HES/HEY network 1
11.24 TWIST1 TCF3 RUNX2 BGLAP
19
Development_Hedgehog and PTH signaling pathways in bone and cartilage development 23
11.05 RUNX2 IBSP COL1A2 BGLAP
20
Osteoblast Signaling 1
10.73 IBSP BGLAP
21
FGF signaling pathway 1
10.69 RUNX2 FGFR2 FGFR1 CBL BGLAP
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GO Terms for Saethre-Chotzen Syndrome

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Cellular components related to Saethre-Chotzen Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin GO:0000785 9.17 TWIST2 TWIST1 TCF3 RUNX2 MSX2 HAND2

Biological processes related to Saethre-Chotzen Syndrome according to GeneCards Suite gene sharing:

(show all 24)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 10.06 TWIST2 TWIST1 RECQL4 MSX2 HAND2 FGFR3
2 negative regulation of transcription, DNA-templated GO:0045892 10.01 TWIST2 TWIST1 RUNX2 MSX2 FERD3L
3 negative regulation of apoptotic process GO:0043066 9.99 TWIST2 TWIST1 HAND2 CBL CASP2
4 skeletal system development GO:0001501 9.8 RUNX2 FGFR3 FGFR1 COL1A2 BGLAP
5 positive regulation of kinase activity GO:0033674 9.76 FGFR3 FGFR2 FGFR1
6 cellular response to growth factor stimulus GO:0071363 9.74 TWIST1 IBSP BGLAP
7 bone development GO:0060348 9.73 TWIST1 FGFR2 BGLAP
8 fibroblast growth factor receptor signaling pathway GO:0008543 9.73 FGFR3 FGFR2 FGFR1 CBL
9 ossification GO:0001503 9.72 TWIST1 RUNX2 MSX2 IBSP BGLAP
10 negative regulation of osteoblast differentiation GO:0045668 9.71 TWIST2 TWIST1 HAND2
11 skeletal system morphogenesis GO:0048705 9.67 RUNX2 FGFR2 FGFR1
12 embryonic cranial skeleton morphogenesis GO:0048701 9.65 TWIST1 RUNX2 FGFR2
13 osteoblast differentiation GO:0001649 9.65 TWIST1 RUNX2 MSX2 IBSP BGLAP
14 osteoblast development GO:0002076 9.62 RUNX2 BGLAP
15 regulation of osteoblast differentiation GO:0045667 9.61 RUNX2 FGFR2
16 positive regulation of transcription regulatory region DNA binding GO:2000679 9.6 TWIST1 HAND2
17 endochondral bone growth GO:0003416 9.58 FGFR3 FGFR2
18 cranial suture morphogenesis GO:0060363 9.55 TWIST1 MSX2
19 positive regulation of phospholipase activity GO:0010518 9.54 FGFR3 FGFR2 FGFR1
20 cardiac neural crest cell development involved in outflow tract morphogenesis GO:0061309 9.52 TWIST1 HAND2
21 cardiac neural crest cell migration involved in outflow tract morphogenesis GO:0003253 9.51 TWIST1 HAND2
22 odontogenesis GO:0042476 9.46 TWIST1 FGFR2 COL1A2 BGLAP
23 developmental process GO:0032502 9.26 TWIST2 TWIST1 HAND2 FERD3L
24 bone mineralization GO:0030282 9.02 IBSP FGFR3 FGFR2 COL1A2 BGLAP

Molecular functions related to Saethre-Chotzen Syndrome according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.47 TWIST2 TWIST1 TCF3 RUNX2 RECQL4 MSX2
2 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 10 FERD3L HAND2 MSX2 RUNX2 TCF3 TWIST1
3 protein homodimerization activity GO:0042803 9.85 TWIST1 TCF3 HAND2 FGFR2 FGFR1 CRPPA
4 protein domain specific binding GO:0019904 9.81 TWIST1 RUNX2 CASP2 ACSL3
5 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 9.8 TWIST2 TWIST1 MSX2 HAND2 FERD3L
6 transcription regulatory region sequence-specific DNA binding GO:0000976 9.78 HAND2 MSX2 RUNX2 TCF3
7 transmembrane receptor protein tyrosine kinase activity GO:0004714 9.61 FGFR3 FGFR2 FGFR1
8 E-box binding GO:0070888 9.5 HAND2 TCF3 TWIST1
9 bHLH transcription factor binding GO:0043425 9.43 RUNX2 TCF3 TWIST1
10 protein dimerization activity GO:0046983 9.35 FERD3L HAND2 TCF3 TWIST1 TWIST2
11 fibroblast growth factor binding GO:0017134 9.33 FGFR3 FGFR2 FGFR1
12 fibroblast growth factor-activated receptor activity GO:0005007 8.8 FGFR3 FGFR2 FGFR1
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Sources for Saethre-Chotzen Syndrome

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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-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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