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Craniosynostosis and dental anomalies(CRSDA)

MedGen UID:
481703
Concept ID:
C3280073
Disease or Syndrome
Synonyms: CRSDA; KREIBORG-PAKISTANI SYNDROME
SNOMED CT: Kreiborg Pakistani syndrome (773332008); Craniosynostosis and dental anomalies syndrome (773332008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): IL11RA (9p13.3)
 
Monarch Initiative: MONDO:0013615
OMIM®: 614188
Orphanet: ORPHA284149

Definition

CRSDA is an autosomal recessive disorder characterized by craniosynostosis, maxillary hypoplasia, and dental anomalies, including malocclusion, delayed and ectopic tooth eruption, and/or supernumerary teeth. Some patients also display minor digit anomalies, such as syndactyly and/or clinodactyly (summary by Nieminen et al., 2011). [from OMIM]

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).
Short phalanx of finger
MedGen UID:
163753
Concept ID:
C0877165
Finding
Short (hypoplastic) phalanx of finger, affecting one or more phalanges.
Broad hallux
MedGen UID:
401165
Concept ID:
C1867131
Finding
Visible increase in width of the hallux without an increase in the dorso-ventral dimension.
Clinodactyly
MedGen UID:
1644094
Concept ID:
C4551485
Congenital Abnormality
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
2-3 toe syndactyly
MedGen UID:
1645640
Concept ID:
C4551570
Congenital Abnormality
Syndactyly with fusion of toes two and three.
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).
Conductive hearing impairment
MedGen UID:
9163
Concept ID:
C0018777
Disease or Syndrome
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
Absent malleus
MedGen UID:
488922
Concept ID:
C0576900
Finding
Aplasia of the malleus.
Stapes ankylosis
MedGen UID:
350008
Concept ID:
C1861326
Anatomical Abnormality
Stapes ankylosis refers to congenital or acquired fixation of the stapes (the stirrup-shaped small bone or ossicle in the middle ear), which is associated with conductive hearing resulting from impairment of the sound-conduction mechanism (the external auditory canal, tympanic membrane, and/or middle-ear ossicles).
Chiari malformation
MedGen UID:
2065
Concept ID:
C0003803
Congenital Abnormality
Chiari malformation consists of a downward displacement of the cerebellar tonsils and the medulla through the foramen magnum, sometimes causing hydrocephalus as a result of obstruction of CSF outflow.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Syringomyelia
MedGen UID:
21449
Concept ID:
C0039144
Disease or Syndrome
Dilated, glial-lined cavity in spinal cord. This cavity does not communicate with the central canal, and usually is between the dorsal columns unilaterally or bilaterally along the side of the cord.
Crouzon syndrome
MedGen UID:
1162
Concept ID:
C0010273
Disease or Syndrome
Crouzon syndrome is an autosomal dominant disorder characterized by craniosynostosis causing secondary alterations of the facial bones and facial structure. Common features include hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism (Reardon et al., 1994; Glaser et al., 2000).
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.
Dolichocephaly
MedGen UID:
65142
Concept ID:
C0221358
Congenital Abnormality
An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.
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.
Isolated scaphocephaly
MedGen UID:
82712
Concept ID:
C0265534
Congenital Abnormality
Scaphocephaly is a subtype of dolichocephaly where the anterior and posterior aspects of the cranial vault are pointed (boat-shaped). Scaphocephaly is caused by a precocious fusion of sagittal suture without other associated synostosis.
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.
Sagittal craniosynostosis
MedGen UID:
140921
Concept ID:
C0432123
Congenital Abnormality
A kind of craniosynostosis affecting the sagittal suture.
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).
Flat occiput
MedGen UID:
332439
Concept ID:
C1837402
Finding
Reduced convexity of the occiput (posterior part of skull).
Coronal craniosynostosis
MedGen UID:
344694
Concept ID:
C1856266
Congenital Abnormality
Premature closure of the coronal suture of skull.
Prominent metopic ridge
MedGen UID:
387953
Concept ID:
C1857949
Finding
Vertical bony ridge positioned in the midline of the forehead.
Metopic synostosis
MedGen UID:
395990
Concept ID:
C1860819
Congenital Abnormality
Premature fusion of the metopic suture.
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.
Turricephaly
MedGen UID:
1726910
Concept ID:
C5399823
Congenital Abnormality
Tall head relative to width and length.
Chronic otitis media
MedGen UID:
75751
Concept ID:
C0271441
Disease or Syndrome
Chronic otitis media refers to fluid, swelling, or infection of the middle ear that does not heal and may cause permanent damage to the ear.
Dental malocclusion
MedGen UID:
9869
Concept ID:
C0024636
Anatomical Abnormality
Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns.
Dental crowding
MedGen UID:
11850
Concept ID:
C0040433
Finding
Changes in alignment of teeth in the dental arch
Teeth, supernumerary
MedGen UID:
21210
Concept ID:
C0040457
Anatomical Abnormality
The presence of one or more teeth additional to the normal number.
Delayed eruption of teeth
MedGen UID:
68678
Concept ID:
C0239174
Finding
Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age.
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.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Wide nose
MedGen UID:
140869
Concept ID:
C0426421
Finding
Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae.
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).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Flat forehead
MedGen UID:
347463
Concept ID:
C1857485
Finding
A forehead with abnormal flatness.
Sloping forehead
MedGen UID:
346640
Concept ID:
C1857679
Finding
Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.
Fingernail dysplasia
MedGen UID:
866606
Concept ID:
C4020952
Disease or Syndrome
An abnormality of the development of the fingernails.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.
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).
Papilledema
MedGen UID:
10565
Concept ID:
C0030353
Finding
Papilledema refers to edema (swelling) of the optic disc secondary to any factor which increases cerebral spinal fluid pressure.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCraniosynostosis and dental anomalies
Follow this link to review classifications for Craniosynostosis and dental anomalies in Orphanet.

Professional guidelines

PubMed

Costello BJ, Edwards SP
Oral Maxillofac Surg Clin North Am 2010 Feb;22(1):5-15. doi: 10.1016/j.coms.2009.10.003. PMID: 20159474
Vilan Xavier AC, Pinto Silva LC, Oliveira P, Villamarim Soares R, de Almeida Cruz R
Spec Care Dentist 2008 May-Jun;28(3):96-100. doi: 10.1111/j.1754-4505.2008.00019.x. PMID: 18489656
Ferraro NF
Clin Plast Surg 1991 Apr;18(2):291-307. PMID: 2065490

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
Ferri J, Schlund M, Touzet-Roumazeille S
J Craniofac Surg 2021 Jan-Feb 01;32(1):141-148. doi: 10.1097/SCS.0000000000007154. PMID: 33027175
Hermann CD, Hyzy SL, Olivares-Navarrete R, Walker M, Williams JK, Boyan BD, Schwartz Z
J Dent Res 2016 Jul;95(8):846-52. Epub 2016 Apr 13 doi: 10.1177/0022034516643315. PMID: 27076448
Vargervik K, Rubin MS, Grayson BH, Figueroa AA, Kreiborg S, Shirley JC, Simmons KE, Warren SM
Am J Orthod Dentofacial Orthop 2012 Apr;141(4 Suppl):S68-73. doi: 10.1016/j.ajodo.2011.12.013. PMID: 22449601
Vilan Xavier AC, Pinto Silva LC, Oliveira P, Villamarim Soares R, de Almeida Cruz R
Spec Care Dentist 2008 May-Jun;28(3):96-100. doi: 10.1111/j.1754-4505.2008.00019.x. PMID: 18489656

Diagnosis

Chitran P, Nair Sreela LS, Mathew P, Prasad TS
J Ayub Med Coll Abbottabad 2021 Jan-Mar;33(1):155-158. PMID: 33774974
Robinson ME, AlQuorain H, Murshed M, Rauch F
Pediatr Nephrol 2020 Oct;35(10):1843-1854. Epub 2019 Aug 8 doi: 10.1007/s00467-019-04290-y. PMID: 31392510
López-Estudillo AS, Rosales-Bérber MA, Ruiz-Rodríguez S, Pozos-Guillén A, Noyola-Frías MÁ, Garrocho-Rangel A
Med Oral Patol Oral Cir Bucal 2017 Nov 1;22(6):e660-e668. doi: 10.4317/medoral.21628. PMID: 29053644Free PMC Article
Lubinsky M, Kantaputra PN
Am J Med Genet A 2016 Oct;170(10):2611-6. Epub 2016 Jun 2 doi: 10.1002/ajmg.a.37763. PMID: 27250821
Mornet E
Orphanet J Rare Dis 2007 Oct 4;2:40. doi: 10.1186/1750-1172-2-40. PMID: 17916236Free PMC Article

Therapy

Robinson ME, AlQuorain H, Murshed M, Rauch F
Pediatr Nephrol 2020 Oct;35(10):1843-1854. Epub 2019 Aug 8 doi: 10.1007/s00467-019-04290-y. PMID: 31392510
Shin HR, Bae HS, Kim BS, Yoon HI, Cho YD, Kim WJ, Choi KY, Lee YS, Woo KM, Baek JH, Ryoo HM
Hum Mol Genet 2018 Nov 15;27(22):3827-3839. doi: 10.1093/hmg/ddy252. PMID: 30007339Free PMC Article
Sánchez Meraz W, Arredondo Hérnandez R, Avalos Sanchez D, Mariel Murga H, Javier Gutiérrez Cantu F, Mariel Cárdenas J
Invest Clin 2016 Sep;57(3):259-66. PMID: 29938478
Lebuis A, Bortoluzzi P, Huynh N, Bach N
J Craniofac Surg 2015 Sep;26(6):1893-9. doi: 10.1097/SCS.0000000000002018. PMID: 26355976
Spolyar JL, Vasileff W, MacIntosh RB
Cleft Palate Craniofac J 1993 Nov;30(6):528-39; discussion 539-41. doi: 10.1597/1545-1569_1993_030_0528_iccaid_2.3.co_2. PMID: 8280730

Prognosis

Korakavi N, Prokop JW, Seaver LH
Am J Med Genet A 2019 Apr;179(4):668-673. Epub 2019 Feb 27 doi: 10.1002/ajmg.a.61070. PMID: 30811827
Rothenbuhler A, Fadel N, Debza Y, Bacchetta J, Diallo MT, Adamsbaum C, Linglart A, Di Rocco F
J Bone Miner Res 2019 Mar;34(3):490-496. Epub 2018 Nov 20 doi: 10.1002/jbmr.3614. PMID: 30352126Free PMC Article
Agochukwu NB, Solomon BD, Doherty ES, Muenke M
J Craniofac Surg 2012 May;23(3):664-8. doi: 10.1097/SCS.0b013e31824db8bb. PMID: 22565872Free PMC Article
Mornet E
Orphanet J Rare Dis 2007 Oct 4;2:40. doi: 10.1186/1750-1172-2-40. PMID: 17916236Free PMC Article
Ferraro NF
Clin Plast Surg 1991 Apr;18(2):291-307. PMID: 2065490

Clinical prediction guides

Kobayashi Y, Ogura K, Hikita R, Tsuji M, Moriyama K
Eur J Orthod 2021 Jan 29;43(1):36-44. doi: 10.1093/ejo/cjaa015. PMID: 32144423
Rothenbuhler A, Fadel N, Debza Y, Bacchetta J, Diallo MT, Adamsbaum C, Linglart A, Di Rocco F
J Bone Miner Res 2019 Mar;34(3):490-496. Epub 2018 Nov 20 doi: 10.1002/jbmr.3614. PMID: 30352126Free PMC Article
López-Estudillo AS, Rosales-Bérber MA, Ruiz-Rodríguez S, Pozos-Guillén A, Noyola-Frías MÁ, Garrocho-Rangel A
Med Oral Patol Oral Cir Bucal 2017 Nov 1;22(6):e660-e668. doi: 10.4317/medoral.21628. PMID: 29053644Free PMC Article
Vargervik K, Rubin MS, Grayson BH, Figueroa AA, Kreiborg S, Shirley JC, Simmons KE, Warren SM
Am J Orthod Dentofacial Orthop 2012 Apr;141(4 Suppl):S68-73. doi: 10.1016/j.ajodo.2011.12.013. PMID: 22449601
Mustafa D, Lucas VS, Junod P, Evans R, Mason C, Roberts GJ
Cleft Palate Craniofac J 2001 Nov;38(6):629-35. doi: 10.1597/1545-1569_2001_038_0629_tdhacr_2.0.co_2. PMID: 11681997

Recent systematic reviews

López-Estudillo AS, Rosales-Bérber MA, Ruiz-Rodríguez S, Pozos-Guillén A, Noyola-Frías MÁ, Garrocho-Rangel A
Med Oral Patol Oral Cir Bucal 2017 Nov 1;22(6):e660-e668. doi: 10.4317/medoral.21628. PMID: 29053644Free PMC Article
Saltaji H, Altalibi M, Major MP, Al-Nuaimi MH, Tabbaa S, Major PW, Flores-Mir C
J Oral Maxillofac Surg 2014 May;72(5):959-72. Epub 2013 Oct 9 doi: 10.1016/j.joms.2013.09.039. PMID: 24280172

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