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Cleidocranial dysplasia 2(CLCD2)

MedGen UID:
1824016
Concept ID:
C5774243
Disease or Syndrome
Synonym: CLCD2
 
Gene (location): CBFB (16q22.1)
 
Monarch Initiative: MONDO:0859307
OMIM®: 620099

Definition

Cleidocranial dysplasia-2 (CLCD2) is characterized by clavicular anomalies, ranging from unilateral 'clavicula bipartita' to bilateral clavicular aplasia, and dental anomalies, including delayed or absent eruption of deciduous teeth and supernumerary teeth. Skull abnormalities such as delayed closure of fontanels have been reported; other skeletal features include delayed bone age, short distal phalanges, and pseudoepiphyses of the metacarpals and/or metatarsals. Phenotypic variability, including intrafamilial, has been observed (Beyltjens et al., 2023). For a general phenotypic description and a discussion of genetic heterogeneity of cleidocranial dysplasia, see CLCD1 (119600). [from OMIM]

Clinical features

From HPO
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Coxa valga
MedGen UID:
116080
Concept ID:
C0239137
Finding
Coxa valga is a deformity of the hip in which the angle between the femoral shaft and the femoral neck is increased compared to age-adjusted values (about 150 degrees in newborns gradually reducing to 120-130 degrees in adults).
Broad thumb
MedGen UID:
140880
Concept ID:
C0426891
Finding
Increased thumb width without increased dorso-ventral dimension.
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Short distal phalanx of finger
MedGen UID:
326590
Concept ID:
C1839829
Finding
Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.
Delayed ossification of carpal bones
MedGen UID:
374771
Concept ID:
C1841684
Finding
Ossification of carpal bones occurs later than age-adjusted norms.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
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.
Plagiocephaly
MedGen UID:
78562
Concept ID:
C0265529
Congenital Abnormality
Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.
Congenital pseudoarthrosis of clavicle
MedGen UID:
75577
Concept ID:
C0265565
Congenital Abnormality
The two portions of the clavicle (corresponding to the two primary ossification centers of the clavicle) are connected by a fibrous bridge that is contiguous with the periosteum, and a synovial membrane develops, resulting in a clavicle with a bipartite appearance radiographically. Congenital pseudarthrosis of the clavicle generally presents as a painless mass or swelling over the clavicle.
Short clavicles
MedGen UID:
96529
Concept ID:
C0426799
Congenital Abnormality
Reduced length of the clavicles.
Down-sloping shoulders
MedGen UID:
346461
Concept ID:
C1856872
Finding
Low set, steeply sloping shoulders.
Aplastic clavicle
MedGen UID:
341820
Concept ID:
C1857665
Congenital Abnormality
Absence of the clavicles as a developmental defect.
Wide anterior fontanel
MedGen UID:
400926
Concept ID:
C1866134
Finding
Enlargement of the anterior fontanelle with respect to age-dependent norms.
Delayed pubic bone ossification
MedGen UID:
357116
Concept ID:
C1866710
Finding
Delayed maturation and calcification of the pubic bone.
Teeth, supernumerary
MedGen UID:
21210
Concept ID:
C0040457
Anatomical Abnormality
The presence of one or more teeth additional to the normal number.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Pointed chin
MedGen UID:
336193
Concept ID:
C1844505
Finding
A marked tapering of the lower face to the chin.
Delayed eruption of primary teeth
MedGen UID:
341477
Concept ID:
C1849538
Finding
Delayed tooth eruption affecting the primary dentition.

Professional guidelines

PubMed

Daskalogiannakis J, Piedade L, Lindholm TC, Sándor GK, Carmichael RP
J Can Dent Assoc 2006 May;72(4):337-42. PMID: 16684478

Recent clinical studies

Etiology

Faria-Teixeira MC, Tordera C, Salvado E Silva F, Vaz-Carneiro A, Iglesias-Linares A
Pediatr Res 2024 May;95(6):1455-1475. Epub 2024 Feb 12 doi: 10.1038/s41390-023-02907-5. PMID: 38347173Free PMC Article
Shih-Wei Cheng E, Tsuji M, Suzuki S, Moriyama K
Eur J Orthod 2022 Dec 1;44(6):711-722. doi: 10.1093/ejo/cjac039. PMID: 35833575
Nahm NJ, Makarewich CA, Rosenwasser KA, Herzenberg JE, McClure PK
J Pediatr Orthop 2022 Jul 1;42(6):e630-e635. Epub 2022 Mar 29 doi: 10.1097/BPO.0000000000002148. PMID: 35348473
Tsuji M, Suzuki H, Suzuki S, Moriyama K
Congenit Anom (Kyoto) 2020 Jul;60(4):106-114. Epub 2019 Oct 23 doi: 10.1111/cga.12358. PMID: 31599034Free PMC Article
Kaplan SB, Kemp SS, Oh KS
Radiol Clin North Am 1991 Mar;29(2):195-218. PMID: 1998047

Diagnosis

Guo X, Duan X
Clin Genet 2023 Sep;104(3):287-297. Epub 2023 Jul 13 doi: 10.1111/cge.14400. PMID: 37448157
Mestre VF, Spoladori IC, Osiak LB, Paiva WJM, Ferreira de Lima RL, Silveira BC, Salles MJS
Gen Dent 2022 Jul-Aug;70(4):59-66. PMID: 35749249
Koduru Laxmi S, Misra SR, Panda S, Mohanty N
BMJ Case Rep 2022 Feb 28;15(2) doi: 10.1136/bcr-2021-248673. PMID: 35228252Free PMC Article
Farrow E, Nicot R, Wiss A, Laborde A, Ferri J
J Craniofac Surg 2018 Mar;29(2):382-389. doi: 10.1097/SCS.0000000000004200. PMID: 29189406
Kerr HD
J Rheumatol 1988 Feb;15(2):359-61. PMID: 3361545

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
Takaki N, Mori J, Matsuo S, Osamura T, Michigami T
BMC Pediatr 2020 Jan 16;20(1):19. doi: 10.1186/s12887-020-1914-8. PMID: 31948427Free PMC Article
Çamtosun E, Akıncı A, Demiral E, Tekedereli İ, Sığırcı A
J Clin Res Pediatr Endocrinol 2019 Sep 3;11(3):301-305. Epub 2018 Nov 23 doi: 10.4274/jcrpe.galenos.2018.2018.0211. PMID: 30468148Free PMC Article
Becker A, Casap N, Chaushu S
Orthod Craniofac Res 2009 May;12(2):82-93. doi: 10.1111/j.1601-6343.2009.01441.x. PMID: 19419451
Kerr HD
J Rheumatol 1988 Feb;15(2):359-61. PMID: 3361545

Prognosis

Siddique AW, Ahmed Z, Haider A, Khalid H, Karim T
J Ayub Med Coll Abbottabad 2019 Apr-Jun;31(2):290-292. PMID: 31094135
Ma D, Wang X, Guo J, Zhang J, Cai T
Medicine (Baltimore) 2018 Aug;97(32):e11328. doi: 10.1097/MD.0000000000011328. PMID: 30095610Free PMC Article
Hsueh SJ, Lee NC, Yang SH, Lin HI, Lin CH
BMC Neurol 2017 Jan 6;17(1):2. doi: 10.1186/s12883-016-0781-2. PMID: 28056872Free PMC Article
Stevenson DA, Carey JC, Byrne JL, Srisukhumbowornchai S, Feldkamp ML
Am J Med Genet A 2012 May;158A(5):1046-54. Epub 2012 Mar 27 doi: 10.1002/ajmg.a.35327. PMID: 22461456
Kaplan SB, Kemp SS, Oh KS
Radiol Clin North Am 1991 Mar;29(2):195-218. PMID: 1998047

Clinical prediction guides

Mestre VF, Spoladori IC, Osiak LB, Paiva WJM, Ferreira de Lima RL, Silveira BC, Salles MJS
Gen Dent 2022 Jul-Aug;70(4):59-66. PMID: 35749249
Thaweesapphithak S, Saengsin J, Kamolvisit W, Theerapanon T, Porntaveetus T, Shotelersuk V
J Appl Oral Sci 2022;30:e20220028. Epub 2022 Jun 6 doi: 10.1590/1678-7757-2022-0028. PMID: 35674542Free PMC Article
Roomaney IA, Chetty M
Orthod Craniofac Res 2021 May;24(2):194-205. Epub 2020 Sep 28 doi: 10.1111/ocr.12426. PMID: 32920986
Pawłowska E, Wójcik KA, Synowiec E, Szczepańska J, Błasiak J
Acta Biochim Pol 2015;62(1):123-6. Epub 2015 Mar 5 doi: 10.18388/abp.2014_866. PMID: 25738174
Kaplan SB, Kemp SS, Oh KS
Radiol Clin North Am 1991 Mar;29(2):195-218. PMID: 1998047

Recent systematic reviews

Guo X, Duan X
Clin Genet 2023 Sep;104(3):287-297. Epub 2023 Jul 13 doi: 10.1111/cge.14400. PMID: 37448157
Roomaney IA, Chetty M
Orthod Craniofac Res 2021 May;24(2):194-205. Epub 2020 Sep 28 doi: 10.1111/ocr.12426. PMID: 32920986

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