Campomelic Dysplasia

A congenital disorder of CHONDROGENESIS and OSTEOGENESIS characterized by hypoplasia of endochondral bones. In most cases there is a curvature of the long bones especially the TIBIA with dimpling of the skin over the bowed areas, malformation of the pelvis and spine, 11 pairs of ribs, hypoplastic scapulae, club feet, micrognathia, CLEFT PALATE, tracheobronchomalacia, and in some patients male-to-female sex reversal (SEX REVERSAL, GONADAL). Most patients die in the neonatal period of respiratory distress. Campomelic dysplasia is associated with haploinsufficiency of the SOX9 TRANSCRIPTION FACTOR gene.

Also Known As:

Networked: 43 relevant articles (0 outcomes, 1 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Congenital Abnormalities (Deformity)
2.	Osteogenesis Imperfecta (Lobstein Disease)
3.	Dwarfism
4.	CHARGE Syndrome
5.	XX Testicular Disorders of Sex Development 46

Experts

1.	Lefebvre, Véronique: 3 articles (01/2021 - 04/2013)
2.	Scherer, Gerd: 3 articles (05/2017 - 06/2003)
3.	Harley, V R: 3 articles (07/2001 - 05/2001)
4.	Pop, Ramona: 2 articles (05/2017 - 06/2005)
5.	Petit, Florence: 2 articles (11/2015 - 12/2013)
6.	Bhattaram, Pallavi: 2 articles (06/2015 - 04/2013)
7.	Mead, Timothy J: 2 articles (06/2015 - 04/2013)
8.	Wang, Qiuqing: 2 articles (06/2015 - 04/2013)
9.	Wegner, Michael: 2 articles (06/2010 - 06/2003)
10.	Angelozzi, Marco: 1 article (01/2021)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Campomelic Dysplasia:

1.	Proteoglycans (Proteoglycan)IBA 02/01/1987 - "A comprehensive study (bone roentgenography, arteriography, gross dissection, microscopy of the long bones, and biochemical study of proteoglycan-aggregates in the hyaline cartilage) of the lower limbs in a full-term stillborn with the campomelic syndrome was performed. "
2.	Transcription Factors (Transcription Factor)IBA 01/01/2023 - "Haploinsufficiency for SOX9, the master chondrogenesis transcription factor, can underlie campomelic dysplasia (CD), an autosomal dominant skeletal malformation syndrome, because heterozygous Sox9 null mice recapitulate the bent limb (campomelia) and some other phenotypes associated with CD. " 01/01/2022 - "Novel SRY-box transcription factor 9 variant in campomelic dysplasia and the location of missense and nonsense variants along the protein domains: A case report." 06/23/2015 - "Two decades after the discovery that heterozygous mutations within and around SOX9 cause campomelic dysplasia, a generalized skeleton malformation syndrome, it is well established that SOX9 is a master transcription factor in chondrocytes. " 01/01/2011 - "Campomelic dysplasia (CD, MIM 114290) is a rare, often lethal, dominantly inherited, congenital skeletal dysplasia, associated with male-to-female autosomal sex reversal and due to de novo mutations of the SOX9 gene, a tissue-specific transcription factor gene involved both in skeletogenesis and male sexual differentiation. " 08/01/2002 - "Haploinsufficiency of SOX9, which encodes a homeodomain transcription factor, results in Campomelic dysplasia. "
3.	SOX9 Transcription FactorIBA 05/01/2003 - "Mutations in the transcription factor SOX9 give rise to campomelic dysplasia, a syndrome characterized by skeletal abnormalities and XY sex reversal. " 07/27/2001 - "Human mutations in the transcription factor SOX9 cause campomelic dysplasia/autosomal sex reversal. " 01/01/2021 - "The transcription factor SOX9 is required for embryonic chondrogenesis, but its postnatal roles remain unclear, despite evidence that it is down-regulated in osteoarthritis and heterozygously inactivated in campomelic dysplasia, a severe skeletal dysplasia characterized postnatally by small stature and kyphoscoliosis. " 12/01/2014 - "The transcription factor Sox9 was first discovered in patients with campomelic dysplasia, a haploinsufficiency disorder with skeletal deformities caused by dysregulation of Sox9 expression during chondrogenesis. " 12/01/2013 - "Heterozygous loss-of-function coding-sequence mutations of the transcription factor SOX9 cause campomelic dysplasia, a rare skeletal dysplasia with congenital bowing of long bones (campomelia), hypoplastic scapulae, a missing pair of ribs, pelvic, and vertebral malformations, clubbed feet, Pierre Robin sequence (PRS), facial dysmorphia, and disorders of sex development. "
4.	DNA (Deoxyribonucleic Acid)IBA 11/16/2022 - "We created a mouse model for the campomelic dysplasia SOX9Y440X mutation, which truncates the transactivation domain but leaves DNA binding and dimerization intact. " 06/01/2010 - "Heterozygous SOX9 mutations allowing for residual DNA-binding and transcriptional activation lead to the acampomelic variant of campomelic dysplasia." 07/27/2001 - "Compound effects of point mutations causing campomelic dysplasia/autosomal sex reversal upon SOX9 structure, nuclear transport, DNA binding, and transcriptional activation." 06/15/2003 - "Loss of DNA-dependent dimerization of the transcription factor SOX9 as a cause for campomelic dysplasia."
5.	Proteins (Proteins, Gene)FDA Link 06/01/1997 - "These results demonstrate that COL2A1 expression is directly regulated by SOX9 protein in vivo and implicate abnormal regulation of COL2A1 during, chondrogenesis as a cause of the skeletal abnormalities associated with campomelic dysplasia." 03/01/1995 - "This localization, as well as the potential role of a mammalian Polycomb-like protein, suggests a potential involvement in two different pathologies: the campomelic syndrome, an inherited disorder, and neoplastic disorders linked to allele loss already described in this region." 05/11/2001 - "The campomelic dysplasia/autosomal sex reversal protein SOX9 is an important developmental transcription factor, required for correct bone and testis formation. "
6.	H-Y AntigenIBA 05/01/1984 - "Ethiopatogenical factors are widely discussed, and special correlation between campomelic dysplasia and sexual reverse, is noted, according to new concepts on H-Y antigen. " 01/01/1981 - "It appears that the mutation leading to campomelic dysplasia interferes with normal H-Y antigen expression." 01/01/1981 - "The "sex- reversal" (chromosomal male Leads to phenotypic female) previously noted in patients with autosomal recessive campomelic dysplasia thus may be mediated through lack of detectable H-Y antigen on the cell surface. " 01/01/1981 - "Two XY females with ovarian gonadal differentiation and typical clinical features of campomelic dysplasia could be tested for H-Y antigen and were found to be H-Y negative." 01/01/1981 - "Absence of H-Y antigen in an XY female with campomelic dysplasia."
7.	Nonsense Codon (Nonsense Mutation)IBA 01/01/2011 - "A novel SOX9 nonsense mutation, q401x, in a case of campomelic dysplasia with XY sex reversal." 06/01/2005 - "A homozygous nonsense mutation in SOX9 in the dominant disorder campomelic dysplasia: a case of mitotic gene conversion."
8.	CollagenIBA 06/01/1991 - "Review of the genetic map of the inverted region identified potential "structural" genes including the Hox-2-homeobox gene and the collagen gene, COLIA1, which may be involved in the pathogenesis of campomelic syndrome." 04/01/1997 - "We speculate that in campomelic dysplasia a decrease in SOX9 activity would inhibit production of collagen II, and eventually other cartilage matrix proteins, leading to major skeletal anomalies."
9.	N- (4'- fluorobutyrophenone)- 4- (4- chlorophenyl)pyridinium (HPP(+))IBA 11/01/2015 - "Osteogenesis imperfecta (OI) and campomelic dysplasia (CD) are the main differential diagnoses of severe HPP, so that in case of negative result for ALPL mutations, OI and CD genes had often to be analyzed, lengthening the time before diagnosis. " 01/01/2019 - "This review focuses on the role of fetal and neonatal imaging modalities in the differential diagnosis of perinatal HPP from other skeletal dysplasias (e.g., osteogenesis imperfecta, campomelic dysplasia, achondrogenesis subtypes, hypochondrogenesis, cleidocranial dysplasia). "
10.	AmphiregulinIBA 10/26/2010 - "IGFBP-rP1 could upreguate Transgelin (TAGLN), downregulate SRY (sex determining region Y)-box 9(campomelic dysplasia, autosomal sex-reversal) (SOX9), insulin receptor substrate 1(IRS1), cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) (CDKN2B), amphiregulin(schwannoma-derived growth factor) (AREG) and immediate early response 5-like(IER5L) in RKO, SW620 and CW2 colon cancer cells, verified by Real time Reverse Transcription Polymerase Chain Reaction (rtRT-PCR). "

Therapies and Procedures

1.	Airway Management 10/01/2011 - "Campomelic dysplasia: airway management in two patients and an update on clinical-molecular correlations in the head and neck."
2.	Osteotomy 03/01/1983 - "In this specimen, metatarsal capsulotomies were required to realign the forefoot, and the osteotomies of the tibia and tibula were required to straighten the angular deformities characteristic of camptomelic dysplasia, as well as the significant external torsion of these bones."
3.	Castration 12/01/1995 - "phenotypic females with campomelic dysplasia should undergo gonadectomy if their karyotype includes a Y chromosome or fragment."