Details of Disease

General Information of Disease (ID: DIS2OHLA)

• Disease Name: Cleidocranial dysplasia 1
• Synonyms: cleidocranial dysplasia, forme fruste, with brachydactyly; dysplasia cleidocranial; cleidocranial dysplasia, forme fruste, dental anomalies only; CLCD; CCD; cleidocranial dysostosis; Cleidocranial Dysplasia; Marie-Sainton disease; cleidocranial dysplasia
• Definition: A condition that primarily affects the development of the bones and teeth. Characteristic features include underdeveloped or absent collarbones (clavicles); dental abnormalities; and delayed closing of the spaces between the skull bones (fontanels). Other features may include decreased bone density (osteopenia), osteoporosis, hearing loss, bone abnormalities of the hands, and recurrent sinus and ear infections. CCD is caused by changes (mutations) in the RUNX2 gene and inheritance is autosomal dominant. It may be inherited from an affected parent or occur due to a new mutation in the RUNX2 gene. Management may include dental procedures, treatment of sinus and ear infections, use of helmets for high-risk activities, and/or surgery for skeletal problems.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DIS9SPWW: Osteochondrodysplasia
  DIS5Z8U6: Skeletal dysplasia
  DIS2OHLA: Cleidocranial dysplasia 1
• Disease Identifiers:
  MONDO ID: MONDO_0007340
  MESH ID: D002973
  UMLS CUI: C0008928
  OMIM ID: 119600
  MedGen ID: 3486
  Orphanet ID: 1452
  SNOMED CT ID: 65976001

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
RYR1	TTU5CIX	moderate	Biomarker	[1]
CEBPB	TTUI35N	Strong	Biomarker	[2]
RUNX2	TTD6SZ8	Definitive	Autosomal dominant	[3]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC26A3	DTN1FMD	Limited	Biomarker	[4]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MYL3	OTKD3RSX	Limited	Altered Expression	[5]
IBSP	OT29944Y	Strong	Altered Expression	[6]
RNF146	OTE4CO7E	Strong	Biomarker	[7]
RPTOR	OT4TQZ9F	Strong	Biomarker	[8]
TCTE1	OTWL4LDO	Strong	Genetic Variation	[9]
RUNX2	OT97RQQM	Definitive	Autosomal dominant	[3]

References

• [1] Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and genetic spectrum.Neurology. 2013 Apr 23;80(17):1584-9. doi: 10.1212/WNL.0b013e3182900380. Epub 2013 Apr 3.
• [2] Prospective signs of cleidocranial dysplasia in Cebpb deficiency.J Biomed Sci. 2014 May 13;21(1):44. doi: 10.1186/1423-0127-21-44.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea: A Nationwide Study in Japan.J Pediatr. 2019 Nov;214:151-157.e6. doi: 10.1016/j.jpeds.2019.07.039. Epub 2019 Aug 30.
• [5] Myosin light chain gene expression associated with disease states of the human heart.J Mol Cell Cardiol. 1993 May;25(5):577-85. doi: 10.1006/jmcc.1993.1067.
• [6] Whole-exome sequencing identification of a novel splicing mutation of RUNX2 in a Chinese family with cleidocranial dysplasia.Arch Oral Biol. 2019 Apr;100:49-56. doi: 10.1016/j.archoralbio.2019.02.005. Epub 2019 Feb 15.
• [7] Ubiquitin ligase RNF146 coordinates bone dynamics and energy metabolism.J Clin Invest. 2017 Jun 30;127(7):2612-2625. doi: 10.1172/JCI92233. Epub 2017 Jun 5.
• [8] mTOR/Raptor signaling is critical for skeletogenesis in mice through the regulation of Runx2 expression.Cell Death Differ. 2017 Nov;24(11):1886-1899. doi: 10.1038/cdd.2017.110. Epub 2017 Jul 7.
• [9] Genetic mapping of cleidocranial dysplasia and evidence of a microdeletion in one family.Hum Mol Genet. 1995 Jan;4(1):71-5. doi: 10.1093/hmg/4.1.71.