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Craniosynostosis 2(CRS2)

MedGen UID:
346753
Concept ID:
C1858160
Disease or Syndrome
Synonyms: Craniosynostosis Boston type; Craniosynostosis Warman type; CRS2; MSX2-Related Craniosynostosis; Warman-Mulliken-Hayward syndrome
SNOMED CT: Craniosynostosis Boston type (720817008); Craniosynostosis Warman type (720817008); Warman Mulliken Hayward syndrome (720817008)
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.
 
Gene (location): MSX2 (5q35.2)
 
Monarch Initiative: MONDO:0011481
OMIM®: 604757
Orphanet: ORPHA1541

Definition

Craniosynostosis 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). For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100). [from OMIM]

Clinical features

From HPO
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.
Triphalangeal thumb
MedGen UID:
66029
Concept ID:
C0241397
Congenital Abnormality
A thumb with three phalanges in a single, proximo-distal axis. Thus, this term applies if the thumb has an accessory phalanx, leading to a digit like appearance of the thumb.
Headache
MedGen UID:
9149
Concept ID:
C0018681
Sign or Symptom
Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
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.
Craniosynostosis syndrome
MedGen UID:
1163
Concept ID:
C0010278
Disease or Syndrome
Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
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.
Trigonocephaly
MedGen UID:
82713
Concept ID:
C0265535
Congenital Abnormality
Wedge-shaped, or triangular head, with the apex of the triangle at the midline of the forehead and the base of the triangle at the occiput.
Metopic synostosis
MedGen UID:
395990
Concept ID:
C1860819
Congenital Abnormality
Premature fusion of the metopic suture.
Wormian bones
MedGen UID:
766814
Concept ID:
C3553900
Congenital Abnormality
The presence of extra bones within a cranial suture. Wormian bones are irregular isolated bones which appear in addition to the usual centers of ossification of the cranium.
Bicoronal synostosis
MedGen UID:
866810
Concept ID:
C4021164
Congenital Abnormality
Synostosis affecting the right and the left coronal suture.
Unicoronal synostosis
MedGen UID:
892477
Concept ID:
C4023418
Anatomical Abnormality
Synostosis affecting only one of the coronal sutures.
Turricephaly
MedGen UID:
1726910
Concept ID:
C5399823
Congenital Abnormality
Tall head relative to width and length.
Teeth, supernumerary
MedGen UID:
21210
Concept ID:
C0040457
Anatomical Abnormality
The presence of one or more teeth additional to the normal number.
Cleft soft palate
MedGen UID:
98471
Concept ID:
C0432098
Congenital Abnormality
Cleft of the soft palate (also known as the velum, or muscular palate) as a result of a developmental defect occurring between the 7th and 12th week of pregnancy. Cleft soft palate can cause functional abnormalities of the Eustachian tube with resulting middle ear anomalies and hearing difficulties, as well as speech problems associated with hypernasal speech due to velopharyngeal insufficiency.
Hypermetropia
MedGen UID:
43780
Concept ID:
C0020490
Disease or Syndrome
An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Hypotelorism
MedGen UID:
96107
Concept ID:
C0424711
Finding
Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).
Visual field defect
MedGen UID:
854603
Concept ID:
C3887875
Finding
An absolute or relative reduction in the extent of the normal field of vision.

Professional guidelines

PubMed

Gavril EC, Nucă I, Pânzaru MC, Ivanov AV, Mihai CT, Antoci LM, Ciobanu CG, Rusu C, Popescu R
Genes (Basel) 2023 Feb 11;14(2) doi: 10.3390/genes14020465. PMID: 36833393Free PMC Article
Shen W, Cui J, Chen J, Yi J, Kong L, Sun B
J Craniofac Surg 2022 Mar-Apr 01;33(2):654-656. doi: 10.1097/SCS.0000000000008289. PMID: 34690305
Kajdic N, Spazzapan P, Velnar T
Bosn J Basic Med Sci 2018 May 20;18(2):110-116. doi: 10.17305/bjbms.2017.2083. PMID: 28623672Free PMC Article

Recent clinical studies

Etiology

Martin M, Hill C, Bewley S, MacLennan AH, Braillon A
Birth Defects Res 2022 Jan 1;114(1):13-16. Epub 2021 Dec 5 doi: 10.1002/bdr2.1967. PMID: 34866359
Taylor JA, Bartlett SP
Plast Reconstr Surg 2017 Jul;140(1):82e-93e. doi: 10.1097/PRS.0000000000003524. PMID: 28654610
Martini M, Röhrig A, Reich RH, Messing-Jünger M
J Craniomaxillofac Surg 2017 Mar;45(3):395-400. Epub 2016 Dec 21 doi: 10.1016/j.jcms.2016.12.018. PMID: 28108236
Sherrod BA, Johnston JM, Rocque BG
J Neurosurg Pediatr 2016 Sep;18(3):350-62. Epub 2016 May 17 doi: 10.3171/2016.2.PEDS15604. PMID: 27184348Free PMC Article
Persing JA
Plast Reconstr Surg 2008 Apr;121(4 Suppl):1-11. doi: 10.1097/01.prs.0000305929.40363.bf. PMID: 18379381

Diagnosis

Grewal JS, Cohn JE, Burdett J, Tampio A, Licata J, Davis WJ 3rd, Tatum SA, Nicholas BD
Cleft Palate Craniofac J 2022 May;59(5):652-658. Epub 2021 May 18 doi: 10.1177/10556656211017795. PMID: 34000844
Golinko MS, Atwood DN, Ocal E
Childs Nerv Syst 2018 Mar;34(3):517-525. Epub 2017 Nov 6 doi: 10.1007/s00381-017-3648-y. PMID: 29110198
Tahiri Y, Bartlett SP, Gilardino MS
Plast Reconstr Surg 2017 Jul;140(1):177e-191e. doi: 10.1097/PRS.0000000000003473. PMID: 28654618
Persing JA
Plast Reconstr Surg 2008 Apr;121(4 Suppl):1-11. doi: 10.1097/01.prs.0000305929.40363.bf. PMID: 18379381
Tharanon W, Sinn DP, Hobar PC, Sklar FH, Salomon J
J Craniofac Surg 1998 Sep;9(5):441-4; discussion 445-7. doi: 10.1097/00001665-199809000-00008. PMID: 9780913

Therapy

Martin M, Hill C, Bewley S, MacLennan AH, Braillon A
Birth Defects Res 2022 Jan 1;114(1):13-16. Epub 2021 Dec 5 doi: 10.1002/bdr2.1967. PMID: 34866359
Martini M, Röhrig A, Reich RH, Messing-Jünger M
J Craniomaxillofac Surg 2017 Mar;45(3):395-400. Epub 2016 Dec 21 doi: 10.1016/j.jcms.2016.12.018. PMID: 28108236
Tharanon W, Sinn DP, Hobar PC, Sklar FH, Salomon J
J Craniofac Surg 1998 Sep;9(5):441-4; discussion 445-7. doi: 10.1097/00001665-199809000-00008. PMID: 9780913
Silver RK, MacGregor SN, Muhlbach LH, Knutel TA, Kambich MP
Prenat Diagn 1994 Jun;14(6):421-7. doi: 10.1002/pd.1970140602. PMID: 7937577

Prognosis

Grewal JS, Cohn JE, Burdett J, Tampio A, Licata J, Davis WJ 3rd, Tatum SA, Nicholas BD
Cleft Palate Craniofac J 2022 May;59(5):652-658. Epub 2021 May 18 doi: 10.1177/10556656211017795. PMID: 34000844
Fearon JA, Ditthakasem K, Herbert M, Kolar J
Plast Reconstr Surg 2017 Jul;140(1):138-145. doi: 10.1097/PRS.0000000000003422. PMID: 28654600
Martini M, Röhrig A, Reich RH, Messing-Jünger M
J Craniomaxillofac Surg 2017 Mar;45(3):395-400. Epub 2016 Dec 21 doi: 10.1016/j.jcms.2016.12.018. PMID: 28108236
Persing JA
Plast Reconstr Surg 2008 Apr;121(4 Suppl):1-11. doi: 10.1097/01.prs.0000305929.40363.bf. PMID: 18379381
Binitie OP
West Afr J Med 1992 Jan-Mar;11(1):7-12. PMID: 1637744

Clinical prediction guides

Grewal JS, Cohn JE, Burdett J, Tampio A, Licata J, Davis WJ 3rd, Tatum SA, Nicholas BD
Cleft Palate Craniofac J 2022 May;59(5):652-658. Epub 2021 May 18 doi: 10.1177/10556656211017795. PMID: 34000844
Fearon JA, Ditthakasem K, Herbert M, Kolar J
Plast Reconstr Surg 2017 Jul;140(1):138-145. doi: 10.1097/PRS.0000000000003422. PMID: 28654600
Michalski AM, Richardson SD, Browne ML, Carmichael SL, Canfield MA, VanZutphen AR, Anderka MT, Marshall EG, Druschel CM
Am J Med Genet A 2015 May;167A(5):1071-81. Epub 2015 Feb 25 doi: 10.1002/ajmg.a.36865. PMID: 25711982
Persing JA
Plast Reconstr Surg 2008 Apr;121(4 Suppl):1-11. doi: 10.1097/01.prs.0000305929.40363.bf. PMID: 18379381
Silver RK, MacGregor SN, Muhlbach LH, Knutel TA, Kambich MP
Prenat Diagn 1994 Jun;14(6):421-7. doi: 10.1002/pd.1970140602. PMID: 7937577

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