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Cleidocranial dysostosis(CCD)

MedGen UID:
3486
Concept ID:
C0008928
Disease or Syndrome
Synonyms: CCD; Cleidocranial Dysplasia; Marie-Sainton disease
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, 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.
not genetically inherited
MedGen UID:
832438
Concept ID:
CN227390
Finding
Source: Orphanet
clinical entity without genetic inheritance.
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Cleidocranial dysostosis (65976001); Cleidocranial dysplasia (65976001); Craniocleidodysostosis (65976001); CCD - Cleidocranial dysplasia (65976001); CLCD - Cleidocranial dysplasia (65976001)
 
Gene (location): RUNX2 (6p21.1)
OMIM®: 119600
Orphanet: ORPHA1452

Disease characteristics

Excerpted from the GeneReview: Cleidocranial Dysplasia Spectrum Disorder
Cleidocranial dysplasia (CCD) spectrum disorder is a skeletal dysplasia that represents a clinical continuum ranging from classic CCD (triad of delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and dental abnormalities) to mild CCD to isolated dental anomalies without the skeletal features. Most individuals come to diagnosis because they have classic features. At birth, affected individuals typically have abnormally large, wide-open fontanelles that may remain open throughout life. Clavicular hypoplasia can result in narrow, sloping shoulders that can be opposed at the midline. Moderate short stature may be observed, with most affected individuals being shorter than their unaffected sibs. Dental anomalies may include supernumerary teeth, eruption failure of the permanent teeth, and presence of the second permanent molar with the primary dentition. Individuals with CCD spectrum disorder are at increased risk of developing recurrent sinus infections, recurrent ear infections leading to conductive hearing loss, and upper-airway obstruction. Intelligence is typically normal. [from GeneReviews]
Authors:
Keren Machol  |  Roberto Mendoza-Londono  |  Brendan Lee   view full author information

Additional descriptions

From OMIM
The main clinical features of CCD include persistently open skull sutures with bulging calvaria, hypoplasia or aplasia of the clavicles permitting abnormal facility in apposing the shoulders, wide pubic symphysis, short middle phalanx of the fifth fingers, dental anomalies, and often vertebral malformation. See 168550 for a discussion of the combination of cleidocranial dysplasia and parietal foramina. Pycnodysostosis (265800) and mandibuloacral dysplasia (248370) are disorders to be considered in the differential diagnosis of cleidocranial dysplasia. Acroosteolysis and bone sclerosis with tendency to fracture are differentiating features of pycnodysostosis. Mundlos (1999) provided a review of the clinical features of cleidocranial dysplasia and the molecular basis of this disorder.  http://www.omim.org/entry/119600
From GHR
Cleidocranial dysplasia is a condition that primarily affects development of the bones and teeth. Signs and symptoms of cleidocranial dysplasia can vary widely in severity, even within the same family.Individuals with cleidocranial dysplasia usually have underdeveloped or absent collarbones, also called clavicles ("cleido-" in the condition name refers to these bones). As a result, their shoulders are narrow and sloping, can be brought unusually close together in front of the body, and in some cases can be made to meet in the middle of the body. Delayed maturation of the skull (cranium) is also characteristic of this condition, including delayed closing of the growth lines where the bones of the skull meet (sutures) and larger than normal spaces (fontanelles) between the skull bones that are noticeable as "soft spots" on the heads of infants. The fontanelles normally close in early childhood, but they may remain open throughout life in people with this disorder. Some individuals with cleidocranial dysplasia have extra pieces of bone called Wormian bones within the sutures.Affected individuals are often shorter than other members of their family at the same age. Many also have short, tapered fingers and broad thumbs; flat feet; bowed legs or knock knees; short shoulder blades (scapulae); and an abnormal curvature of the spine (scoliosis). Typical facial features include a wide, short skull (brachycephaly); a prominent forehead; wide-set eyes (hypertelorism); a flat nose; and a small upper jaw.Individuals with cleidocranial dysplasia often have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture, at a relatively early age. Women with cleidocranial dysplasia have an increased risk of requiring a cesarean section when delivering a baby, due to a narrow pelvis preventing passage of the infant's head.Dental abnormalities are very common in cleidocranial dysplasia and can include delayed loss of the primary (baby) teeth; delayed appearance of the secondary (adult) teeth; unusually shaped, peg-like teeth; misalignment of the teeth and jaws (malocclusion); and extra teeth, sometimes accompanied by cysts in the gums.In addition to skeletal and dental abnormalities, people with cleidocranial dysplasia may have hearing loss and are prone to sinus and ear infections. Some young children with this condition are mildly delayed in the development of motor skills such as crawling and walking, but intelligence is unaffected.  https://ghr.nlm.nih.gov/condition/cleidocranial-dysplasia

Clinical features

From HPO
Moderately short stature
MedGen UID:
348380
Concept ID:
C1861519
Finding
A moderate degree of short stature, more than -3 SD but not more than -4 SD from mean corrected for age and sex.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A general term for the complete or partial loss of the ability to hear from one or both ears.
Syringomyelia
MedGen UID:
21449
Concept ID:
C0039144
Disease or Syndrome
A rare disorder characterized by the formation of a cyst in the spinal cord. It results in weakness, pain, and stiffness in the shoulders, arms, legs, or back. It may be associated with Chiari malformation. Other causes include spinal cord injury, inflammation, or tumor.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Congenital anomaly of abnormally short fingers or toes.
Coxa vara
MedGen UID:
116081
Concept ID:
C0239138
Finding
Hip deformity in which the femoral neck leans forward resulting in a decrease in the angle between femoral neck and its shaft. It may be congenital often syndromic, acquired, or developmental.
Short middle phalanx of the 5th finger
MedGen UID:
322335
Concept ID:
C1834060
Finding
Absence or underdevelopment (hypoplasia) of the middle phalanx of the fifth finger.
Short femoral neck
MedGen UID:
373033
Concept ID:
C1836184
Finding
An abnormally short femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft).
Cone-shaped epiphyses of the phalanges of the hand
MedGen UID:
347156
Concept ID:
C1859480
Finding
A cone-shaped appearance of the epiphyses of the fingers of the hand, producing a 'ball-in-a-socket' appearance. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of a phalanx.
Long second metacarpal
MedGen UID:
350045
Concept ID:
C1861531
Finding
Short middle phalanx of the 2nd finger
MedGen UID:
867077
Concept ID:
C4021435
Anatomical Abnormality
Hypoplasia (congenital reduction in size) of the middle phalanx of the second finger, also known as the index finger.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Hypoplasia of dental enamel
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
A form of amelogenesis imperfecta characterized by incomplete formation of the dental enamel and transmitted as an X-linked or autosomal dominant trait.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Abnormally increased curvature of the thoracic portion of the spine.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
A congenital abnormality of the jaws (particularly the mandible) in which they are unusually small. This condition is not always pathological and may correct itself as the patient matures; however, it may also present as a birth defect in multiple syndromes.
Increased bone mineral density
MedGen UID:
10502
Concept ID:
C0029464
Disease or Syndrome
Abnormally high bone density.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
A congenital or acquired spinal deformity characterized by lateral curvature of the spine.
Spondylolisthesis
MedGen UID:
52470
Concept ID:
C0038016
Disease or Syndrome
Spondylolisthesis is defined as forward slipping of a vertebral body on the one below it. Spondylolysis is defined as a defect in the pars interarticularis without vertebral slipping (summary by Wiltse et al., 1975).
Spondylolysis
MedGen UID:
21294
Concept ID:
C0038018
Disease or Syndrome
A defect in the pars interarticularis of a vertebral bone.
Cervical rib
MedGen UID:
102359
Concept ID:
C0158779
Congenital Abnormality
A supernumerary rib developing from an abnormal enlargement of the costal element of the C7 vertebra. This anomaly is found in 1-2% of the population and can put pressure on adjacent structures causing CERVICAL RIB SYNDROME; THORACIC OUTLET SYNDROME; or other conditions.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
A skeletal deformity characterized by an unusually prominent forehead. Causes include acromegaly, Hurler syndrome, Silver-Russell syndrome, and thalassemia major.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Congenital anomaly of abnormally short fingers or toes.
Wormian bones
MedGen UID:
65163
Concept ID:
C0222716
Body Part, Organ, or Organ Component
Coxa vara
MedGen UID:
116081
Concept ID:
C0239138
Finding
Hip deformity in which the femoral neck leans forward resulting in a decrease in the angle between femoral neck and its shaft. It may be congenital often syndromic, acquired, or developmental.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Short clavicles
MedGen UID:
96529
Concept ID:
C0426799
Congenital Abnormality
Reduced length of the clavicles.
Short ribs
MedGen UID:
98094
Concept ID:
C0426817
Finding
Reduced rib length.
Increased susceptibility to fractures
MedGen UID:
234655
Concept ID:
C1390474
Finding
An abnormally increased tendency to fractures of bones caused by an abnormal reduction in bone strength that is generally associated with an increased risk of fracture.
Short middle phalanx of the 5th finger
MedGen UID:
322335
Concept ID:
C1834060
Finding
Absence or underdevelopment (hypoplasia) of the middle phalanx of the fifth finger.
Short femoral neck
MedGen UID:
373033
Concept ID:
C1836184
Finding
An abnormally short femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft).
Large foramen magnum
MedGen UID:
336194
Concept ID:
C1844508
Finding
An abnormal increase in the size of the foramen magnum.
Hypoplastic scapulae
MedGen UID:
337579
Concept ID:
C1846434
Finding
Underdeveloped scapula.
Persistent open anterior fontanelle
MedGen UID:
376607
Concept ID:
C1849537
Finding
The anterior fontanelle generally ossifies by around the 18th month of life. A persistent open anterior fontanelle is diagnosed if closure is delayed beyond this age.
Absent frontal sinuses
MedGen UID:
343405
Concept ID:
C1855669
Finding
Aplasia of frontal sinus.
Parietal bossing
MedGen UID:
347377
Concept ID:
C1857126
Finding
Parietal bossing is a marked prominence in the parietal region.
Absent paranasal sinuses
MedGen UID:
346522
Concept ID:
C1857131
Finding
Aplasia of the paranasal sinuses.
Wide pubic symphysis
MedGen UID:
387763
Concept ID:
C1857190
Finding
Abnormally increased width of the pubic symphysis is the midline cartilaginous joint uniting the superior rami of the left and right pubic bones.
Aplastic clavicles
MedGen UID:
341820
Concept ID:
C1857665
Congenital Abnormality
Absence of the clavicles as a developmental defect.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Anatomical Abnormality
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Thickened calvaria
MedGen UID:
346823
Concept ID:
C1858452
Finding
The presence of an abnormally thick calvaria.
Cone-shaped epiphyses of the phalanges of the hand
MedGen UID:
347156
Concept ID:
C1859480
Finding
A cone-shaped appearance of the epiphyses of the fingers of the hand, producing a 'ball-in-a-socket' appearance. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of a phalanx.
Hypoplastic frontal sinuses
MedGen UID:
349225
Concept ID:
C1859682
Finding
Underdevelopment of frontal sinus.
Abnormal facility in opposing the shoulders
MedGen UID:
348379
Concept ID:
C1861517
Finding
Long second metacarpal
MedGen UID:
350045
Concept ID:
C1861531
Finding
Hypoplastic iliac wing
MedGen UID:
351279
Concept ID:
C1865027
Anatomical Abnormality
Underdevelopment of the ilium ala.
Delayed pubic bone ossification
MedGen UID:
357116
Concept ID:
C1866710
Finding
Delayed maturation and calcification of the pubic bone.
Short middle phalanx of the 2nd finger
MedGen UID:
867077
Concept ID:
C4021435
Anatomical Abnormality
Hypoplasia (congenital reduction in size) of the middle phalanx of the second finger, also known as the index finger.
Hypoplasia of dental enamel
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
A form of amelogenesis imperfecta characterized by incomplete formation of the dental enamel and transmitted as an X-linked or autosomal dominant trait.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
A congenital abnormality of the jaws (particularly the mandible) in which they are unusually small. This condition is not always pathological and may correct itself as the patient matures; however, it may also present as a birth defect in multiple syndromes.
Increased number of teeth
MedGen UID:
21210
Concept ID:
C0040457
Finding
An extra tooth, erupted or unerupted, resembling or unlike the other teeth in the group to which it belongs. Its presence may cause malposition of adjacent teeth or prevent their eruption.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
A skeletal deformity characterized by an unusually prominent forehead. Causes include acromegaly, Hurler syndrome, Silver-Russell syndrome, and thalassemia major.
Wormian bones
MedGen UID:
65163
Concept ID:
C0222716
Body Part, Organ, or Organ Component
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.
High, narrow palate
MedGen UID:
324787
Concept ID:
C1837404
Finding
The presence of a high and narrow palate.
Large foramen magnum
MedGen UID:
336194
Concept ID:
C1844508
Finding
An abnormal increase in the size of the foramen magnum.
Persistent open anterior fontanelle
MedGen UID:
376607
Concept ID:
C1849537
Finding
The anterior fontanelle generally ossifies by around the 18th month of life. A persistent open anterior fontanelle is diagnosed if closure is delayed beyond this age.
Delayed eruption of primary teeth
MedGen UID:
341477
Concept ID:
C1849538
Finding
Delayed tooth eruption affecting the primary dentition.
Delayed eruption of permanent teeth
MedGen UID:
340353
Concept ID:
C1849540
Finding
Delayed tooth eruption affecting the secondary dentition.
Absent frontal sinuses
MedGen UID:
343405
Concept ID:
C1855669
Finding
Aplasia of frontal sinus.
Parietal bossing
MedGen UID:
347377
Concept ID:
C1857126
Finding
Parietal bossing is a marked prominence in the parietal region.
Absent paranasal sinuses
MedGen UID:
346522
Concept ID:
C1857131
Finding
Aplasia of the paranasal sinuses.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Anatomical Abnormality
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Thickened calvaria
MedGen UID:
346823
Concept ID:
C1858452
Finding
The presence of an abnormally thick calvaria.
Hypoplastic frontal sinuses
MedGen UID:
349225
Concept ID:
C1859682
Finding
Underdevelopment of frontal sinus.
Midface retrusion
MedGen UID:
388629
Concept ID:
C2673410
Finding
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).
Hypoplasia of dental enamel
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
A form of amelogenesis imperfecta characterized by incomplete formation of the dental enamel and transmitted as an X-linked or autosomal dominant trait.
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 (145410), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCleidocranial dysostosis
Follow this link to review classifications for Cleidocranial dysostosis in Orphanet.

Recent clinical studies

Etiology

Kulczyk T, Przystańska A, Rewekant A, Turska-Malińska R, Czajka-Jakubowska A
Ann Anat 2018 Jan;215:78-82. Epub 2017 Sep 6 doi: 10.1016/j.aanat.2017.08.002. PMID: 28889021
Farronato G, Maspero C, Farronato D, Gioventù S
Angle Orthod 2009 Jan;79(1):178-85. doi: 10.2319/111307-393.1. PMID: 19123713
Angle AD, Rebellato J
Am J Orthod Dentofacial Orthop 2005 Jul;128(1):110-7. doi: 10.1016/j.ajodo.2004.05.019. PMID: 16027635
Hassan J, Sepulveda W, Teixeira J, Garrett C, Fisk NM
Prenat Diagn 1997 Aug;17(8):770-2. PMID: 9267902
Kreiborg S, Jensen BL, Björk A, Skieller V
Am J Orthod 1981 May;79(5):549-57. PMID: 6940449

Diagnosis

Barth FA, Menuci Neto A, Almeida-Pedrin RR, Ladewig VM, Conti ACCF
J Craniofac Surg 2018 Sep;29(6):1642-1647. doi: 10.1097/SCS.0000000000004656. PMID: 29877984
DasGupta R, Jebasingh FK, Asha HS, Thomas N
BMJ Case Rep 2015 Aug 26;2015 doi: 10.1136/bcr-2015-211308. PMID: 26311012Free PMC Article
Gardner MA, Li BC, Wu YW, Slavotinek AM
Pediatr Neurol 2012 Dec;47(6):455-7. doi: 10.1016/j.pediatrneurol.2012.08.009. PMID: 23127269
Lossdörfer S, Abou Jamra B, Rath-Deschner B, Götz W, Abou Jamra R, Braumann B, Jäger A
J Orofac Orthop 2009 Nov;70(6):495-510. Epub 2009 Dec 4 doi: 10.1007/s00056-009-9934-x. PMID: 19960292
Angle AD, Rebellato J
Am J Orthod Dentofacial Orthop 2005 Jul;128(1):110-7. doi: 10.1016/j.ajodo.2004.05.019. PMID: 16027635

Therapy

Svarch E, Menéndez A, Morales M, González A
Haematologia (Budap) 1988;21(2):121-2. PMID: 3166445

Prognosis

Anthonappa RP, Yan-Hui F, King NM, Rabie AB, You-Qiang S
J Oral Pathol Med 2014 Nov;43(10):798-800. Epub 2014 Jun 16 doi: 10.1111/jop.12198. PMID: 24935264
Gardner MA, Li BC, Wu YW, Slavotinek AM
Pediatr Neurol 2012 Dec;47(6):455-7. doi: 10.1016/j.pediatrneurol.2012.08.009. PMID: 23127269
Ramsaran AS, Barclay S, Scipio E, Ogunsalu C
West Indian Med J 2005 Oct;54(5):334-6. doi: 10.1590/s0043-31442005000500012. PMID: 16459518
Angle AD, Rebellato J
Am J Orthod Dentofacial Orthop 2005 Jul;128(1):110-7. doi: 10.1016/j.ajodo.2004.05.019. PMID: 16027635
MILES LE
N Z Med J 1964 Aug;63:491-7. PMID: 14199475

Clinical prediction guides

Anthonappa RP, Yan-Hui F, King NM, Rabie AB, You-Qiang S
J Oral Pathol Med 2014 Nov;43(10):798-800. Epub 2014 Jun 16 doi: 10.1111/jop.12198. PMID: 24935264
Gardner MA, Li BC, Wu YW, Slavotinek AM
Pediatr Neurol 2012 Dec;47(6):455-7. doi: 10.1016/j.pediatrneurol.2012.08.009. PMID: 23127269
Lossdörfer S, Abou Jamra B, Rath-Deschner B, Götz W, Abou Jamra R, Braumann B, Jäger A
J Orofac Orthop 2009 Nov;70(6):495-510. Epub 2009 Dec 4 doi: 10.1007/s00056-009-9934-x. PMID: 19960292
Fukuta Y, Totsuka M, Fukuta Y, Takeda Y, Yoshida Y, Niitsu J, Yamamoto H
J Oral Sci 2001 Jun;43(2):85-9. PMID: 11515602
Nolan G, Hackman A
Br J Psychiatry 1970 May;116(534):543-4. doi: 10.1192/bjp.116.534.543. PMID: 5449139

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