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Saethre-Chotzen syndrome(SCS)

MedGen UID:
64221
Concept ID:
C0175699
Disease or Syndrome
Synonyms: Acrocephalo-syndactyly, type 3; Acrocephaly, skull asymmetry, and mild syndactyly; ACS 3; ACS III; Chotzen syndrome; Saethre-Chotzen Syndrome, FGFR2-Related; SCS
SNOMED CT: Saethre-Chotzen syndrome (83015004); Acrocephalosyndactyly, type III (83015004)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Genes (locations): FGFR2 (10q26.13); TWIST1 (7p21.1)
 
Monarch Initiative: MONDO:0007042
OMIM®: 101400
Orphanet: ORPHA794

Disease characteristics

Excerpted from the GeneReview: Saethre-Chotzen Syndrome
Classic Saethre-Chotzen syndrome (SCS) is characterized by coronal synostosis (unilateral or bilateral), facial asymmetry (particularly in individuals with unicoronal synostosis), strabismus, ptosis, and characteristic appearance of the ear (small pinna with a prominent superior and/or inferior crus). Syndactyly of digits two and three of the hand is variably present. Cognitive development is usually normal, although those with a large genomic deletion are at an increased risk for intellectual challenges. Less common manifestations of SCS include other skeletal findings (parietal foramina, vertebral segmentation defects, radioulnar synostosis, maxillary hypoplasia, ocular hypertelorism, hallux valgus, duplicated or curved distal hallux), hypertelorism, palatal anomalies, obstructive sleep apnea, increased intracranial pressure, short stature, and congenital heart malformations. [from GeneReviews]
Authors:
Emily R Gallagher  |  Chootima Ratisoontorn  |  Michael L Cunningham   view full author information

Additional descriptions

From OMIM
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).  http://www.omim.org/entry/101400
From MedlinePlus Genetics
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.

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.  https://medlineplus.gov/genetics/condition/saethre-chotzen-syndrome

Clinical features

From HPO
Hallux valgus
MedGen UID:
5416
Concept ID:
C0018536
Anatomical Abnormality
Lateral deviation of the great toe (i.e., in the direction of the little toe).
Syndactyly
MedGen UID:
52619
Concept ID:
C0039075
Congenital Abnormality
Webbing or fusion of the fingers or toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers or toes in a proximo-distal axis are referred to as "symphalangism".
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Toe syndactyly
MedGen UID:
75581
Concept ID:
C0265660
Congenital Abnormality
Webbing or fusion of the toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the toes in a proximo-distal axis are referred to as "Symphalangism".
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Absent first metatarsal
MedGen UID:
350160
Concept ID:
C1863382
Finding
A developmental defect characterized by the absence of the first metatarsal bone.
Partial duplication of the distal phalanx of the 3rd finger
MedGen UID:
867003
Concept ID:
C4021360
Anatomical Abnormality
Partial duplication of the distal phalanx of middle finger, seen on x-rays as a broad and/or bifid phalanx.
Partial duplication of the distal phalanx of the 2nd finger
MedGen UID:
867008
Concept ID:
C4021365
Anatomical Abnormality
Partial duplication of the distal phalanx of index finger, seen on x-rays as a broad and/or bifid phalanx.
Abnormal heart morphology
MedGen UID:
6748
Concept ID:
C0018798
Congenital Abnormality
Any structural anomaly of the heart.
Abnormal cardiovascular system morphology
MedGen UID:
892473
Concept ID:
C4049796
Anatomical Abnormality
Any structural anomaly of the heart and blood vessels.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Microtia
MedGen UID:
57535
Concept ID:
C0152423
Congenital Abnormality
Underdevelopment of the external ear.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Intellectual disability, moderate
MedGen UID:
7680
Concept ID:
C0026351
Mental or Behavioral Dysfunction
Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Radioulnar synostosis
MedGen UID:
57861
Concept ID:
C0158761
Congenital Abnormality
An abnormal osseous union (fusion) between the radius and the ulna.
Brachycephaly
MedGen UID:
113165
Concept ID:
C0221356
Congenital Abnormality
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
Hypoplasia of the maxilla
MedGen UID:
66804
Concept ID:
C0240310
Congenital Abnormality
Abnormally small dimension of the Maxilla. Usually creating a malocclusion or malalignment between the upper and lower teeth or resulting in a deficient amount of projection of the base of the nose and lower midface region.
Delayed cranial suture closure
MedGen UID:
75805
Concept ID:
C0277828
Finding
Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age.
Skull asymmetry
MedGen UID:
140861
Concept ID:
C0424690
Finding
Craniosynostosis 4
MedGen UID:
322167
Concept ID:
C1833340
Disease or Syndrome
Craniosynostosis (CRS) is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by Fitzpatrick, 2013). Craniosynostosis-4 (CRS4) includes lambdoid, sagittal, metopic, coronal, and multisuture forms. For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100).
Coronal craniosynostosis
MedGen UID:
344694
Concept ID:
C1856266
Congenital Abnormality
Premature closure of the coronal suture of skull.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Shallow orbits
MedGen UID:
351328
Concept ID:
C1865244
Finding
Reduced depth of the orbits associated with prominent-appearing ocular globes.
Plagiocephaly
MedGen UID:
1825944
Concept ID:
C2081594
Finding
Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.
Abnormal pelvic girdle bone morphology
MedGen UID:
866545
Concept ID:
C4020847
Anatomical Abnormality
An abnormality of the bony pelvic girdle, which is a ring of bones connecting the vertebral column to the femurs.
Prominent crus of helix
MedGen UID:
867019
Concept ID:
C4021377
Anatomical Abnormality
The presence of an abnormally prominent of the crus of the helix. That is, development of the crus helix to the same degree as an average antihelix stem or helix.
Oxycephaly
MedGen UID:
1634950
Concept ID:
C4551646
Congenital Abnormality
Oxycephaly (from Greek oxus, sharp, and kephalos, head) refers to a conical or pointed shape of the skull.
Parietal foramina
MedGen UID:
505331
Concept ID:
CN002451
Finding
The presence of symmetrical and circular openings (foramina) in the parietal bone ranging in size from a few millimeters to several centimeters wide.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Convex nasal ridge
MedGen UID:
66809
Concept ID:
C0240538
Finding
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
Narrow nose
MedGen UID:
98086
Concept ID:
C0426422
Finding
Interalar distance more than 2 SD below the mean for age, or alternatively, an apparently decreased width of the nasal base and alae.
Facial asymmetry
MedGen UID:
266298
Concept ID:
C1306710
Finding
An abnormal difference between the left and right sides of the face.
Narrow palate
MedGen UID:
278045
Concept ID:
C1398312
Finding
Width of the palate more than 2 SD below the mean (objective) or apparently decreased palatal width (subjective).
Long nose
MedGen UID:
326583
Concept ID:
C1839798
Finding
Distance from nasion to subnasale more than two standard deviations above the mean, or alternatively, an apparently increased length from the nasal root to the nasal base.
Low anterior hairline
MedGen UID:
331280
Concept ID:
C1842366
Finding
Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD below the mean. Alternatively, an apparently decreased distance between the hairline and the glabella.
Cleft of chin
MedGen UID:
336544
Concept ID:
C1849227
Finding
A bony peculiarity underlies the Y-shaped fissure of the chin.
Flat face
MedGen UID:
342829
Concept ID:
C1853241
Finding
Absence of concavity or convexity of the face when viewed in profile.
Flat forehead
MedGen UID:
347463
Concept ID:
C1857485
Finding
A forehead with abnormal flatness.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Abnormal nasolacrimal system morphology
MedGen UID:
871343
Concept ID:
C4025835
Anatomical Abnormality
An abnormality of the nasolacrimal drainage system, which serves as a conduit for tear flow from the external eye to the nasal cavity.
Breast carcinoma
MedGen UID:
146260
Concept ID:
C0678222
Neoplastic Process
The presence of a carcinoma of the breast.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Buphthalmos
MedGen UID:
1641795
Concept ID:
C4551507
Congenital Abnormality
Diffusely large eye (with megalocornea) associated with glaucoma.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSaethre-Chotzen syndrome
Follow this link to review classifications for Saethre-Chotzen syndrome in Orphanet.

Professional guidelines

PubMed

Casteleyn T, Horn D, Henrich W, Verlohren S
Arch Gynecol Obstet 2022 Jul;306(1):49-57. Epub 2021 Oct 11 doi: 10.1007/s00404-021-06263-9. PMID: 34633507Free PMC Article
Kutkowska-Kaźmierczak A, Gos M, Obersztyn E
J Appl Genet 2018 May;59(2):133-147. Epub 2018 Feb 1 doi: 10.1007/s13353-017-0423-4. PMID: 29392564
Biamino E, Canale A, Lacilla M, Marinosci A, Dagna F, Genitori L, Peretta P, Silengo M, Albera R, Ferrero GB
Int J Pediatr Otorhinolaryngol 2016 Jun;85:95-8. Epub 2016 Apr 11 doi: 10.1016/j.ijporl.2016.03.038. PMID: 27240504

Recent clinical studies

Etiology

Choi TM, Lijten OW, Mathijssen IMJ, Wolvius EB, Ongkosuwito EM
Clin Oral Investig 2022 Mar;26(3):2927-2936. Epub 2021 Dec 14 doi: 10.1007/s00784-021-04275-y. PMID: 34904178Free PMC Article
Den Ottelander BK, Van Veelen MC, De Goederen R, Van De Beeten SD, Dremmen MH, Loudon SE, Versnel SL, Van Den Ouweland AM, Van Dooren MF, Joosten KF, Mathijssen IM
Dev Med Child Neurol 2021 Jan;63(1):104-110. Epub 2020 Sep 9 doi: 10.1111/dmcn.14670. PMID: 32909287Free PMC Article
Abulezz TA, Allam KA, Wan DC, Lee JC, Kawamoto HK
Ann Plast Surg 2020 Sep;85(3):251-255. doi: 10.1097/SAP.0000000000002391. PMID: 32487807
Kilcoyne S, Luscombe C, Scully P, Jayamohan J, Magdum S, Wall S, Johnson D, Wilkie AOM
J Craniofac Surg 2019 Jul;30(5):1506-1511. doi: 10.1097/SCS.0000000000005241. PMID: 31299755
Pelc A, Mikulewicz M
Dent Med Probl 2018 Apr-Jun;55(2):217-225. doi: 10.17219/dmp/91050. PMID: 30152628

Diagnosis

Abulezz TA, Allam KA, Wan DC, Lee JC, Kawamoto HK
Ann Plast Surg 2020 Sep;85(3):251-255. doi: 10.1097/SAP.0000000000002391. PMID: 32487807
Pelc A, Mikulewicz M
Dent Med Probl 2018 Apr-Jun;55(2):217-225. doi: 10.17219/dmp/91050. PMID: 30152628
Kutkowska-Kaźmierczak A, Gos M, Obersztyn E
J Appl Genet 2018 May;59(2):133-147. Epub 2018 Feb 1 doi: 10.1007/s13353-017-0423-4. PMID: 29392564
Wang JC, Nagy L, Demke JC
Facial Plast Surg Clin North Am 2016 Nov;24(4):531-543. doi: 10.1016/j.fsc.2016.06.008. PMID: 27712819
Reardon W, Winter RM
J Med Genet 1994 May;31(5):393-6. doi: 10.1136/jmg.31.5.393. PMID: 8064818Free PMC Article

Therapy

Yang S, Mathijssen IMJ, Joosten KFM
Eur J Pediatr 2022 Dec;181(12):4191-4197. Epub 2022 Sep 28 doi: 10.1007/s00431-022-04621-6. PMID: 36169714Free PMC Article
Raposo-Amaral CE, de Oliveira YM, Denadai R, Raposo-Amaral CA, Ghizoni E
Childs Nerv Syst 2021 Jun;37(6):2001-2009. Epub 2021 Apr 18 doi: 10.1007/s00381-021-05169-w. PMID: 33866411
Shi J, Cao J, Zhou BP
Curr Pharm Des 2015;21(10):1256-61. doi: 10.2174/1381612821666141211153853. PMID: 25506891Free PMC Article
Goldstein JA, Paliga JT, Bailey RL, Heuer GG, Taylor JA
J Craniofac Surg 2013 Jul;24(4):1263-7. doi: 10.1097/SCS.0b013e318286081f. PMID: 23851785
Adjaye J, Bolton V, Monk M
Gene 1999 Sep 17;237(2):373-83. doi: 10.1016/s0378-1119(99)00329-7. PMID: 10521661

Prognosis

Prada-Madrid JR, Franco-Chaparro LP, Garcia-Wenninger M, Palomino-Consuegra T, Stanford N, Castañeda-Hernández DA
J Craniofac Surg 2017 May;28(3):675-678. doi: 10.1097/SCS.0000000000003459. PMID: 28468147
Nur BG, Pehlivanoğlu S, Mıhçı E, Calışkan M, Demir D, Alper OM, Kayserili H, Lüleci G
Pediatr Neurol 2014 May;50(5):482-90. Epub 2014 Jan 11 doi: 10.1016/j.pediatrneurol.2014.01.023. PMID: 24656465
Sauerhammer TM, Patel K, Oh AK, Proctor MR, Mulliken JB, Rogers GF
J Craniofac Surg 2014 Mar;25(2):437-40. doi: 10.1097/01.scs.0000436674.59196.cd. PMID: 24448523
Rosen H, Andrews BT, Meara JG, Stoler JM, Mulliken JB, Rogers GF
Plast Reconstr Surg 2011 May;127(5):2014-2020. doi: 10.1097/PRS.0b013e31820cf16a. PMID: 21532428
Trusen A, Beissert M, Collmann H, Darge K
Pediatr Radiol 2003 Mar;33(3):168-72. Epub 2002 Nov 12 doi: 10.1007/s00247-002-0823-3. PMID: 12612814

Clinical prediction guides

Yang S, Mathijssen IMJ, Joosten KFM
Eur J Pediatr 2022 Dec;181(12):4191-4197. Epub 2022 Sep 28 doi: 10.1007/s00431-022-04621-6. PMID: 36169714Free PMC Article
Pelc A, Mikulewicz M
Dent Med Probl 2018 Apr-Jun;55(2):217-225. doi: 10.17219/dmp/91050. PMID: 30152628
Sauerhammer TM, Patel K, Oh AK, Proctor MR, Mulliken JB, Rogers GF
J Craniofac Surg 2014 Mar;25(2):437-40. doi: 10.1097/01.scs.0000436674.59196.cd. PMID: 24448523
Firulli AB, Conway SJ
Curr Med Chem 2008;15(25):2641-7. doi: 10.2174/092986708785908987. PMID: 18855684Free PMC Article
Müller U, Steinberger D, Kunze S
Graefes Arch Clin Exp Ophthalmol 1997 Sep;235(9):545-50. doi: 10.1007/BF00947081. PMID: 9342602

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