Saethre-Chotzen syndrome (SCS)

Was ist Saethre-Chotzen syndrome (SCS)?

Saethre-Chotzen ist eine seltene Erkrankung (Kraniosynostose), die zu einer vorzeitigen Verschmelzung der Schädelknochen führt.

Diese vorzeitige Verschmelzung beeinflusst wiederum die Form von Kopf und Gesicht. Es hat jedoch keinen Einfluss auf die Entwicklung des Gehirns und die intellektuellen Fähigkeiten.

Syndrom Synonyme:
Akrozephalosyndaktylie - Typ III Akrozephalosyndaktylie Typ III Akrozephalosyndaktylie, Typ Iii; Acs3 Akrozephalie, Schädelasymmetrie und leichte Syndaktylie Acs Iii ACSIII Chotzen Syndrom SCS

Was Genveränderungen verursachen Saethre-Chotzen syndrome (SCS)?

Das Syndromes wird vererbt und ist das Ergebnis von Mutationen zum TWIST 1 -Gen. Es wird in einem autosomal dominanten Muster vererbt.

Im Fall einer autosomal dominanten Vererbung ist nur ein Elternteil der Träger der Genmutation, und sie haben eine 50% ige Chance, sie an jedes ihrer Kinder weiterzugeben. Syndromes, die in einer autosomal dominanten Vererbung vererbt werden, werden durch nur eine Kopie der Genmutation verursacht.

Was sind die wichtigsten symptome von Saethre-Chotzen syndrome (SCS)?

Physikalische Merkmale des syndrom Dazu gehören Finger- und Zehenbänder, kleine und ungewöhnlich geformte Ohren, Kleinwuchs, Knochenanomalien in der Wirbelsäule, Krümmung des kleinen Fingers, kurze Finger und Zehen und ein flacher Kopf.

Einzigartige Gesichtszüge des syndrom Dazu gehören eine hohe Stirn, eine Asymmetrie des Gesichts, eine Schnabelnase, weit auseinanderstehende Augen und ein eingedrückter Nasenrücken.

Mögliche klinische Merkmale/Merkmale:
Schmale Nase, Schmaler Gaumen, Lambdoidale Kraniosynostose, Lange Nase, Tief angesetzte, nach hinten gedrehte Ohren, Tief angesetzte Ohren, Niedriger vorderer Haaransatz, Mikrotie, Migräne, Erhöhter Hirndruck, Abnorme Form der Wirbelkörper, Geistige Behinderung, mäßig, Hypertelorismus , Kognitive Beeinträchtigung, Hallux valgus, Hohe Stirn, Hörbehinderung, Kleinwuchs, Sehbehinderung, Hypoplasie des Oberkiefers, Klinodaktylie des 5. Fingers, Gaumenspalte, Fehlbildung des Herzens und der großen Gefäße, Kryptorchismus, Kraniosynostose, Koronale Kraniosynostose , Verzögerter kranialer Nahtverschluss, Schallleitungsschwerhörigkeit, Gesichtsasymmetrie, Fingersyndaktylie, Flache Stirn, Außenohrfehlbildung, Atresie des äußeren Gehörgangs, Malare Abflachung, Brachydaktylie, Fehlen des ersten Metatarsale, Apnoe, Mammakarzinom, Brachyzephalie, Buphthalmus, Konvexe Nasen Kieferkamm, Kinnspalte, Abnormalität der Knochenmorphologie des Beckengürtels, Abnormale Morphologie des Nasen-Tränen-Systems, Autosomal dominant t Vererbung, Plagiocepha

Wie wird jemand getestet? Saethre-Chotzen syndrome (SCS)?

Die ersten Tests für das Saethre-Chotzen-Syndrom können mit einem Screening der Gesichtsanalyse über die FDNA Telehealth Telegenetics-Plattform beginnen, mit der die Schlüsselmarker des Syndroms identifiziert und die Notwendigkeit weiterer Tests aufgezeigt werden können. Eine Konsultation mit einem genetischen Berater und dann einem Genetiker wird folgen. 

Basierend auf dieser klinischen Konsultation mit einem Genetiker werden die verschiedenen Optionen für Gentests geteilt und die Zustimmung für weitere Tests eingeholt.

Medizinische Informationen zu Saethre-Chotzen Syndrom

This form of acrocephalosyndactyly was well reviewed by Pantke et al., (1975). It is characterised by asymmetric facies, brachycephaly, parietal foramina, a broad forehead, ptosis, a beaked nose, loss of the frontonasal angle, low-set ears with folded pinnae and prominent cruri, and minor abnormalities of the hands and feet. The latter consist of soft tissue syndactyly, mild brachydactyly, clinodactyly and hallux valgus. The hallux can be quite broad but is not in varus as seen in Pfeiffer syndrome. Some cases are mistakenly reported as Pfeiffer syndrome because of the broad halluces (see Naveh and Friedman, (1976) for example). Mild mental retardation may be present and craniostenosis can be demonstrated in about 90% of patients.
Cases with 7p21 deletions have many similarities including craniosynostosis and parietal foramina (see Motegi et al., (1985), Kikkawa et al., (1993) and Chotai et al., (1994) for good reviews). The case reported by Grebe et al., (1992) with a 7p15.3-p21.2 or 7p21.3 deletion had many similarities. Note that there may be a gene more proximal to 7p21 that also causes craniosynostosis (Aughton et al., 1991). This gene is probably distinct from the Greig syndrome gene at 7p13. Van Allen et al., (1992) discuss the evidence for a 'craniosynostosis gene' on 15q. They point out that in the mouse there are contiguous homologous regions to human 7p and 15q on mouse chromosome 2, suggesting a cluster of genes important in suture formation in the mouse that has become separated in the human. Zollino et al., (1999) report other cases with a duplication of 15q25.1-qter associated with craniosynostosis. There may be another gene for coronal craniosynostosis on 8q (Fryburg and Golden, 1993). Brueton et al., (1992) found evidence of linkage to markers around 7p21 in Saethre-Chotzen families. Refined localisation was reported by Lewanda et al., (1994) and van Herwerden et al., (1994). Reardon et al., (1993) identified a de novo translocation case with breakpoints at 7p21.2; Reid et al., (1993) similarly identified a translocation case with breakpoints at 7p22. Tsuji et al., (1994) reported a further case with an apparently balanced 6;7 translocation. The breakpoints on 7 were reported as 7p15.3. The explanation for the discrepancy between these breakpoints is not clear. Ma et al., (1996) carried out further linkage studies and discussed the evidence for possibly two loci on 7p. Rose et al., (1994) carried out FISH studies using YACs from the 7p21 region in four translocation cases, including that of Reardon et al., (1993). Wilkie et al., (1995) described the clinical features of the cases in the paper of Rose et al., (1994) in detail. Von Gernet et al., (1996) reported a four-generation family where at least seven individuals have convincing features of Saethre-Chotzen syndrome, but the locus does not appear to map to 7p. Howard et al., (1997) and El Ghouzzi et al., (1997) described mutations in the TWIST gene, which codes for a basic helix-loop-helix transcription factor. Nonsense, missense, insertion and deletion mutations were described. Some of the insertions were in a region of the gene encoding a glycine-rich sequence (Gly)5Ala(Gly)5. However, Elanko et al., (2001) suggest that either deletion of 18 nucleotides or insertion of 3, 15 or 21 nucleotides may be low-frequency polymorphisms without pathological significance. Krebs et al., (1997) showed a breakpoint in a translocation case first reported by Tsuji et al., (1984) mapping 5 kb 3 ' from TWIST, suggesting a positional effect. Further mutations were reported by El Ghouzzi et al., (1999). Further mutations in the TWIST gene were reported by Rose et al., (1997), including 3 cases with a 21bp duplication. Four translocation cases were also examined, and the breakpoints were at least 5kb from TWIST, suggesting a positional effect. Johnson et al., (1998) studied ten patients with Saethre-Chotzen syndrome and found mutations in eight. They also found mutations in two patients out of 43 cases with no clear diagnostic label. Of the ten mutations, four represented significant deletions, one in a 7;8 balanced translocation case. Paznekas et al., (1998) studied 32 cases with a Saethre-Chotzen phenotype and found TWIST mutations in twelve. A Pro250Arg mutation of the FGFR3 gene was found in seven cases and a 6-bp in-frame deletion of the IgII, IgIII linker region of the FGFR2 gene was found in one family. Gripp et al., (1999) reported a case with a stop mutation in TWIST where there was radial aplasia.
El-Ghouzzi et al., (2000) presented evidence suggesting that TWIST mutations resulted in protein degradation or abnormal sub-cellular localisation.
Seto et al., (2001) reported a father and son. The father had very mild features of Saethre-Chotzen syndrome, whereas the son had coronal, metopic and sagittal synostosis together with bilateral radial ray aplasia with an absent thumb on the right. An A466G leading to an Ile156Val substitution was detected. The cases of Gripp et al., (1999) and Seto et al., (2001) have overlap with Baller-Gerold syndrome. Boeck et al., (2001) reported a mother and son with a condition where there was an 11 bp deletion (127del11). The son had recurrent infections and hyper IgE. However, this was not seen in the mother. Two other cases had a large deletion (3.5-10.2Mb) and were associated with developmental delay. Further cases with submicroscopic deletions involving the TWIST gene were reported by Gripp et al., (2001). The family reported by Maw et al., (1996) with an atypical form of Blepharophimosis-ptosis-epicanthus inversus syndrome mapping to 7p13-7p21 have now been found to carry a TWIST mutation (Dollfus et al., 2001).
Chun et al., (2002) studied nine families and FGFR3 Pro250Arg mutations in four cases, TWIST mutations in three cases and a deletion involving the TWIST gene in two cases. Cai et al., (2003) studied 55 patients with features of Saethre-Chotzen syndrome, 11% were detected to have deletions by real-time gene dosage analysis. Two patients had a translocation or inversion at least 260 kb 3' of the gene, suggesting they had position-effect mutations. Of the 37 patients with classic features of Saethre-Chotzen syndrome, the overall detection rate for TWIST mutations was 68%. The risk for developmental delay in patients with deletions involving the TWIST gene was approximately 90%. Gripp et al., (2003) comment that anal atresia may be a low-frequency association.
De Heer et al., (2004), reported an interesting family with many features of BPES (see elsewhere). Two had a craniosynostosis, and they turned out to have TWIST mutations as found in Saethre-Chotzen syndrome. Of 47 patients with unilateral coronal synostosis studied by Mulliken et al., (2004), 3 had TWIST mutations, and 2 had FGFR2 mutations. Another FGFR2 mutation was found by Burrone de Freitas et al., (2006), but this family is more likely to have Pfeifer syndrome.
Corsi et al., (2002) studied a semi-dominant allele in the TWIST gene in C.elegans and showed possible dominant negative activity. Similar phenotypes were caused when amino acid substitutions in the DNA binding domain of the protein, associated with Saethre-Chotzen syndrome were engineered into the C.elegans protein. TWIST has been shown to promote tumour growth, so note the case of Saethre-Chotzen reported by Seifert et al., (2006) with a renal cell carcinoma.
Shimada et al. (2013) described a male with Saethre-Chotzen syndrome and microdeletions of 5.5 Mb (4q13.2–q13.3) and 4.1 Mb (7p15.3–p21.1, including TWIST1) with a Saethre–Chotzen-like phenotype, severe intellectual disability and autism. Clinical characteristics were developmental delay, autistic behavior, brachycephalic and acrocephalic head, facial asymmetry, high and narrow forehead, sparse and arched eyebrows, hypertelorism, bilateral blepharophimosis and ptosis, epicanthus inversus, strabismus, depressed and deviated nasal bridge, anteverted nares, maxillary hypoplasia, low set and posteriorly angulated ear with uplifted lobe and prominent crus helices and cutaneous syndactyly between 2nd and 3rd fingers.
Cho et al. (2013) described a male with Saethre-Chotzen syndrome and a148 kb deletion in 7p21.1 region comprising TWIST1 gene. Clinical features were microcephaly, delayed development, hypertelorism, frontal bossing, low-set ears, small pinna with prominent crura, high-arched palate, and single transverse crease on the left hand, but no other limb anomalies. Brain MRI showed fusion of the left coronal and metopic sutures.
Shimbo et al. (2017) reported a male with Saethre-Chotzen syndrome and a de novo 0.9-Mb microdeletion in 7p21 region including TWIST1, NPMIP13, FERD3L, TWISTNB, and HDAC9 genes. Clinical characteristics were unilateral craniosynostosis, plagiocephaly, brachycephaly, wide anterior fontanelle, mild developmental delay, facial asymmetry, low-set frontal hairline, ptosis, hypertelorism, posteriorly rotated ears, mild syndactyly, and cleft palate.
Zhou et. al. (2018) described two unrelated patients with heterozygous mutations in the 5′ untranslated region of the TWIST1 gene. Clinical characteristics did not differ from previously reported.

* This information is courtesy of the L M D.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]

Erhalten Sie eine schnellere und genauere Genetische Diagnostik!

Mehr als 250,000 Patienten erfolgreich analysiert!
Warten Sie nicht Jahre auf eine Diagnose. Handeln Sie jetzt und sparen Sie wertvolle Zeit.

Los geht's!

"Unser Weg zu einer Diagnose seltener Krankheiten war eine 5 -jährige Reise, die ich nur als Versuch beschreiben kann, einen Roadtrip ohne Karte zu unternehmen. Wir kannten unseren Ausgangspunkt nicht. Wir kannten unser Ziel nicht. Jetzt haben wir Hoffnung. "

Bild

Paula und Bobby
Eltern von Lillie

Was ist FDNA Telehealth?

FDNA Telehealth ist ein führendes Unternehmen für digitale Gesundheit, das einen schnelleren Zugang zu genauen genetischen Analysen bietet.

Mit einer von führenden Genetikern empfohlenen Krankenhaustechnologie verbindet unsere einzigartige Plattform Patienten mit Genexperten, um ihre dringendsten Fragen zu beantworten und eventuelle Bedenken hinsichtlich ihrer Symptome zu klären.

Vorteile von FDNA Telehealth

FDNA-Symbol

Credibility

Unsere Plattform wird derzeit von über 70% der Genetiker verwendet und wurde zur Diagnose von über 250,000 Patienten weltweit eingesetzt.

FDNA-Symbol

Barrierefreiheit

FDNA Telehealth bietet innerhalb von Minuten eine Gesichtsanalyse und ein Screening, gefolgt von einem schnellen Zugang zu genetischen Beratern und Genetikern.

FDNA-Symbol

Benutzerfreundlichkeit

Unser nahtloser Prozess beginnt mit einer ersten Online-Diagnose durch einen genetischen Berater, gefolgt von Konsultationen mit Genetikern und Gentests.

FDNA-Symbol

Genauigkeit & Präzision

Erweiterte Funktionen und Technologien für künstliche Intelligenz (KI) mit einer Genauigkeitsrate von 90% für eine genauere genetische analyse.

FDNA-Symbol

Preis-Leistungs-Verhältnis

Schnellerer Zugang zu genetischen Beratern, Genetikern, Gentests und einer Diagnose. Falls erforderlich, innerhalb von 24 Stunden. Sparen Sie Zeit und Geld.

FDNA-Symbol

Privatsphäre & Sicherheit

Wir garantieren den größtmöglichen Schutz aller Bilder und Patienteninformationen. Ihre Daten sind immer sicher und verschlüsselt.

FDNA Telehealth kann Sie einer Diagnose näher bringen.
Vereinbaren Sie innerhalb von 72 Stunden ein Online-Treffen zur genetischen Beratung!

EspañolDeutschPortuguêsFrançaisEnglish