# Spondyloepiphyseal dysplasia, Kimberley type
**Spondyloepiphyseal dysplasia, Kimberley type** (SEDK) is a rare, mild, autosomal dominant skeletal dysplasia characterized by short stature, a stocky build, and early-onset osteoarthritis of the weight-bearing joints, caused by pathogenic variants in the aggrecan gene (ACAN, formerly AGC1) at locus 15q26.1.[1](https://www.orpha.net/en/disease/detail/93283) • [2](https://www.ncbi.nlm.nih.gov/medgen/330777) It takes its name from the South African region where the family in which it was first described lived.
| Key fact | Detail |
|---|---|
| Definition | Mild autosomal dominant spondyloepiphyseal dysplasia with short stature, stocky build, and early-onset osteoarthritis of the weight-bearing joints[2](https://www.ncbi.nlm.nih.gov/medgen/330777) |
| Cause | Mutation in the aggrecan gene (ACAN/AGC1, locus 15q26.1)[1](https://www.orpha.net/en/disease/detail/93283) |
| Inheritance | Autosomal dominant; age of onset infancy or neonatal[1](https://www.orpha.net/en/disease/detail/93283) |
| Prevalence | <1 per 1,000,000[1](https://www.orpha.net/en/disease/detail/93283) |
| Radiographic features | Flattened vertebral bodies with sclerosis and prominent endplate irregularity; flattened femoral epiphyses[1](https://www.orpha.net/en/disease/detail/93283) |
| Causative variant | Single-base-pair insertion in exon 12 (c.3986dupC), a frameshift of 212 amino acids ending in a premature stop codon[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC4924316/) |
| Codes | OMIM 608361; ORPHA:93283; ICD-10 Q77.7; ICD-11 LD24.3[1](https://www.orpha.net/en/disease/detail/93283) |
## Clinical features
The main clinical features are proportionate short stature below the 5th percentile for age, a stocky habitus, and early-onset progressive osteoarthropathy of the weight-bearing joints.[1](https://www.orpha.net/en/disease/detail/93283) MedlinePlus describes the osteoarthritis as developing early particularly in the knees, ankles, and hips.[4](https://medlineplus.gov/genetics/gene/acan/) Radiographs show flattened vertebral bodies with sclerosis and prominent endplate irregularity, and flattened femoral epiphyses.[1](https://www.orpha.net/en/disease/detail/93283)
Orphanet's Human Phenotype Ontology annotation lists seven very frequent signs: abnormality of epiphysis morphology, micromelia (short limbs), osteoarthritis, platyspondyly (flattened vertebral bodies), proportionate short stature, short thorax, and spondyloepiphyseal dysplasia itself.[5](https://www.orpha.net/en/disease/sign/93283) MedGen additionally records genu varum and genu valgum (bowlegs and knock knees) and delayed skeletal maturation among the associated clinical features.[2](https://www.ncbi.nlm.nih.gov/medgen/330777)
## Genetics and molecular cause
SEDK is transmitted as an autosomal dominant trait, so an affected person has a 50 percent chance of passing the condition to each child.[1](https://www.orpha.net/en/disease/detail/93283) • [6](https://rarediseases.info.nih.gov/diseases/16814/spondyloepiphyseal-dysplasia-kimberley-type) The condition was first mapped, in a multigenerational South African family of English white descent, to a novel locus on chromosome 15q26.1.[1](https://www.orpha.net/en/disease/detail/93283) • [7](https://research.manchester.ac.uk/en/publications/a-mutation-in-the-variable-repeat-region-of-the-aggrecan-gene-agc/)
The aggrecan gene encodes aggrecan, the core protein of the most abundant proteoglycan of cartilage, a protein with sugar chains attached that gives cartilage its resilience during endochondral bone growth and joint function.[7](https://research.manchester.ac.uk/en/publications/a-mutation-in-the-variable-repeat-region-of-the-aggrecan-gene-agc/) • [4](https://medlineplus.gov/genetics/gene/acan/) In 2005, Lindsay Gleghorn, a researcher at the Wellcome Centre for Cell-Matrix Research, with Rajkumar Ramesar, Peter Beighton of the [University of Cape Town](https://www.edgepedia.org/university-of-cape-town), and Gillian Wallis, screened ACAN in the affected family and identified a single-base-pair insertion within the variable repeat region of exon 12. The insertion causes a frameshift of 212 amino acids, including 22 cysteine residues, followed by a premature stop codon; the authors reported it as the first identification of an AGC1 mutation causing a human disorder.[7](https://research.manchester.ac.uk/en/publications/a-mutation-in-the-variable-repeat-region-of-the-aggrecan-gene-agc/) The variant is cataloged as c.3986dupC, p.Gly1330Trpfs*221.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC4924316/)
ACAN variants cause a wider spectrum of aggrecanopathies beyond SEDK, including spondyloepimetaphyseal dysplasia, aggrecan type (a more severe autosomal recessive disorder), [familial osteochondritis dissecans](https://www.edgepedia.org/familial-osteochondritis-dissecans), and short stature with advanced bone age with or without early-onset osteoarthritis or osteochondritis dissecans.[8](https://www.orpha.net/en/disease/gene/ACAN)
## Epidemiology
Orphanet records a prevalence below 1 per 1,000,000, and the disorder has been described in one multigenerational South African family of English white descent.[1](https://www.orpha.net/en/disease/detail/93283) Symptoms may begin in the newborn period or in infancy.[1](https://www.orpha.net/en/disease/detail/93283) • [6](https://rarediseases.info.nih.gov/diseases/16814/spondyloepiphyseal-dysplasia-kimberley-type) Since the original family, additional reports have described SEDK in other families, including a case caused by a previously undescribed likely pathogenic ACAN variant detected in a proband and his parent.[9](https://www.revcog.org/index.php/ggcl/article/view/2338)
## Relation to other spondyloepiphyseal dysplasias
Spondyloepiphyseal dysplasias (SED) are a heterogeneous group of disorders affecting the vertebrae and epiphyses, the ends of long bones, broadly divided into a congenita form evident at birth and a tarda form evident later.[10](https://www.ncbi.nlm.nih.gov/books/NBK1145/) SEDK differs from the better-known forms in gene and inheritance: the congenita form is caused by COL2A1 variants and presents neonatally with severe disproportionate short stature, while the classic X-linked tarda form is caused by TRAPPC2 variants and is distinguished by later onset and X-linked inheritance.[10](https://www.ncbi.nlm.nih.gov/books/NBK1145/) SEDK is a mild, dominantly inherited member of this group whose distinguishing feature is early-onset osteoarthritis of the weight-bearing joints on a background of proportionate short stature.[2](https://www.ncbi.nlm.nih.gov/medgen/330777)
## Management
No FDA-approved treatments are listed for SEDK, and care is directed at the short stature and the joint disease.[11](https://www.uniterare.org/diseases/spondyloepiphyseal-dysplasia-kimberley-type) In patients with ACAN mutations more broadly, treatment with growth hormone and gonadotropin-releasing hormone analogs has been used to halt bone age progression and improve final adult height.[12](https://www.endotext.org/wp-content/uploads/pdfs/skeletal-dysplasias.pdf) Because aggrecan degeneration also plays a central role in common osteoarthritis, study of aggrecanopathies has been proposed as a route to understanding that condition.[9](https://www.revcog.org/index.php/ggcl/article/view/2338)
## References
1. [Spondyloepiphyseal dysplasia, Kimberley type, Orphanet (ORPHA:93283)](https://www.orpha.net/en/disease/detail/93283)
2. [Spondyloepiphyseal dysplasia, Kimberley type (Concept ID C1842149), MedGen, NCBI](https://www.ncbi.nlm.nih.gov/medgen/330777)
3. [The aggrecanopathies; an evolving phenotypic spectrum of human genetic skeletal diseases, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC4924316/)
4. [ACAN gene, MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/acan/)
5. [Spondyloepiphyseal dysplasia, Kimberley type: Clinical signs and symptoms, Orphanet](https://www.orpha.net/en/disease/sign/93283)
6. [Spondyloepiphyseal dysplasia, Kimberley type, GARD, NIH](https://rarediseases.info.nih.gov/diseases/16814/spondyloepiphyseal-dysplasia-kimberley-type)
7. [Gleghorn L, Ramesar R, Beighton P, Wallis G (2005). A mutation in the variable repeat region of the aggrecan gene (AGC1) causes a form of spondyloepiphyseal dysplasia associated with severe, premature osteoarthritis. American Journal of Human Genetics 77(3):484-490](https://research.manchester.ac.uk/en/publications/a-mutation-in-the-variable-repeat-region-of-the-aggrecan-gene-agc/)
8. [ACAN - aggrecan, Orphanet gene page](https://www.orpha.net/en/disease/gene/ACAN)
9. [Aggrecanopathies: Report of a Spondyloepiphyseal Dysplasia Kimberley type (SEDK) in a family, caused by a previously undescribed likely pathogenic variant of the ACAN gene](https://www.revcog.org/index.php/ggcl/article/view/2338)
10. [X-Linked Spondyloepiphyseal Dysplasia Tarda, GeneReviews, NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK1145/)
11. [Spondyloepiphyseal dysplasia, Kimberley type, UniteRare](https://www.uniterare.org/diseases/spondyloepiphyseal-dysplasia-kimberley-type)
12. [Skeletal dysplasias, Endotext](https://www.endotext.org/wp-content/uploads/pdfs/skeletal-dysplasias.pdf)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Diseases and injuries › Skin and musculoskeletal conditions › Musculoskeletal conditions › Bone disease and injury › Spondylo-epiphyseal and metaphyseal dysplasias*
*Initially written Oct 21, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license