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Cleidocranial dysostosis(CLCD1)

MedGen UID:
3486
Concept ID:
C0008928
Disease or Syndrome
Synonyms: CLCD1; Cleidocranial Dysplasia; CLEIDOCRANIAL DYSPLASIA 1; Marie-Sainton disease
SNOMED CT: Cleidocranial dysostosis (65976001); Cleidocranial dysplasia (65976001); Craniocleidodysostosis (65976001); CCD - Cleidocranial dysplasia (65976001); CLCD - Cleidocranial dysplasia (65976001)
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.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): RUNX2 (6p21.1)
 
Monarch Initiative: MONDO:0007340
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 other skeletal features. Individuals with classic CCD spectrum disorder typically have abnormally large, wide-open fontanelles at birth 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 delayed eruption of secondary dentition, failure to shed the primary teeth, and supernumerary teeth. 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 cleidocranial dysplasia (CLCD) 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. Genetic Heterogeneity of Cleidocranial Dysplasia CLCD2 (620099) is caused by mutation in the CBFB gene (121360) on chromosome 16q22. See 168550 for a discussion of the combination of cleidocranial dysplasia and parietal foramina. 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 MedlinePlus Genetics
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; 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://medlineplus.gov/genetics/condition/cleidocranial-dysplasia

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.
Short middle phalanx of the 5th finger
MedGen UID:
322335
Concept ID:
C1834060
Anatomical Abnormality
Hypoplastic/small middle phalanx of the fifth finger.
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.
Coxa vara
MedGen UID:
1790477
Concept ID:
C5551440
Anatomical Abnormality
Coxa vara includes all forms of decrease of the femoral neck shaft angle (the angle between the neck and the shaft of the femur) to less than 120 degrees.
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).
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 decreased magnitude of the sensory perception of sound.
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.
Hip dislocation
MedGen UID:
42455
Concept ID:
C0019554
Injury or Poisoning
Displacement of the femur from its normal location in the hip joint.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Increased bone mineral density
MedGen UID:
10502
Concept ID:
C0029464
Disease or Syndrome
An abnormal increase of bone mineral density, that is, of the amount of matter per cubic centimeter of bones which is often referred to as osteosclerosis. Osteosclerosis can be detected on radiological examination as an increased whiteness (density) of affected bones.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal 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
Spondylolysis is an osseous defect of the pars interarticularis, thought to be a developmental or acquired stress fracture secondary to chronic low-grade trauma.
Cervical rib
MedGen UID:
102359
Concept ID:
C0158779
Congenital Abnormality
Presence of rib formation in the cervical region.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
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.
Large fontanelles
MedGen UID:
105329
Concept ID:
C0456132
Finding
In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms.
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 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 clavicle
MedGen UID:
341820
Concept ID:
C1857665
Congenital Abnormality
Absence of the clavicles as a developmental defect.
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.
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
Increased range of shoulder movement related to aplasia or hypoplasia of the clavicles that results in the ability to approximate the shoulders in front of the chest.
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.
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.
Respiratory distress
MedGen UID:
96907
Concept ID:
C0476273
Sign or Symptom
Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Enamel hypoplasia
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
Developmental hypoplasia of the dental enamel.
Teeth, supernumerary
MedGen UID:
21210
Concept ID:
C0040457
Anatomical Abnormality
The presence of one or more teeth additional to the normal number.
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).
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.
High, narrow palate
MedGen UID:
324787
Concept ID:
C1837404
Finding
The presence of a high and narrow palate.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
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.
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.
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).
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).

Term Hierarchy

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

Professional guidelines

PubMed

Smylski PT, Woodside DG, Harnett BE
Int J Oral Surg 1974;3(6):380-5. doi: 10.1016/s0300-9785(74)80002-5. PMID: 4217313

Recent clinical studies

Etiology

Cardonick EH, O'Laughlin AE, So SC, Fleischer LT, Akoto S
Eur J Pediatr 2022 Apr;181(4):1763-1766. Epub 2022 Jan 23 doi: 10.1007/s00431-021-04260-3. PMID: 35066626
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
Krishnan SG, Hawkins RJ, Michelotti JD, Litchfield R, Willis RB, Kim YK
Clin Orthop Relat Res 2005 Jun;(435):126-33. PMID: 15930929
Kreiborg S, Jensen BL, Björk A, Skieller V
Am J Orthod 1981 May;79(5):549-57. doi: 10.1016/s0002-9416(81)90465-6. PMID: 6940449

Diagnosis

Cardonick EH, O'Laughlin AE, So SC, Fleischer LT, Akoto S
Eur J Pediatr 2022 Apr;181(4):1763-1766. Epub 2022 Jan 23 doi: 10.1007/s00431-021-04260-3. PMID: 35066626
Villamil V, Pruneda RR, Ibieta MF, Cánovas CS
Pan Afr Med J 2021;38:368. Epub 2021 Apr 15 doi: 10.11604/pamj.2021.38.368.29204. PMID: 34367447Free PMC Article
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
Altschuler EL
Clin Orthop Relat Res 2001 Feb;(383):286-9. doi: 10.1097/00003086-200102000-00033. PMID: 11210965
Hassan J, Sepulveda W, Teixeira J, Garrett C, Fisk NM
Prenat Diagn 1997 Aug;17(8):770-2. PMID: 9267902

Therapy

Cardonick EH, O'Laughlin AE, So SC, Fleischer LT, Akoto S
Eur J Pediatr 2022 Apr;181(4):1763-1766. Epub 2022 Jan 23 doi: 10.1007/s00431-021-04260-3. PMID: 35066626
Svarch E, Menéndez A, Morales M, González A
Haematologia (Budap) 1988;21(2):121-2. PMID: 3166445

Prognosis

Cardonick EH, O'Laughlin AE, So SC, Fleischer LT, Akoto S
Eur J Pediatr 2022 Apr;181(4):1763-1766. Epub 2022 Jan 23 doi: 10.1007/s00431-021-04260-3. PMID: 35066626
Nagasaka S, Suzuki K, Saito T, Tanaka K, Yamamoto J
Childs Nerv Syst 2021 Feb;37(2):683-686. Epub 2020 Jun 5 doi: 10.1007/s00381-020-04689-1. PMID: 32504170
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
Merks JH, Caron HN, Hennekam RC
Am J Med Genet A 2005 Apr 15;134A(2):132-43. doi: 10.1002/ajmg.a.30603. PMID: 15712196

Clinical prediction guides

Cardonick EH, O'Laughlin AE, So SC, Fleischer LT, Akoto S
Eur J Pediatr 2022 Apr;181(4):1763-1766. Epub 2022 Jan 23 doi: 10.1007/s00431-021-04260-3. PMID: 35066626
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. doi: 10.2334/josnusd.43.85. PMID: 11515602

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