Spondyloperipheral dysplasia is a disorder that impairs bone growth. The signs and symptoms of this condition can vary among affected individuals. People with spondyloperipheral dysplasia typically have short stature, with a short torso, short arms and legs, and short fingers and toes (brachydactyly). These parts of the body are not proportional to one another (disproportionate short stature) in people with this condition. Affected individuals also tend to have flattened bones of the spine (platyspondyly) and inward- and upward-turning feet (clubfoot). Some people with spondyloperipheral dysplasia may also experience nearsightedness (myopia) or hearing loss.  

Spondyloperipheral dysplasia is very rare, though the exact prevalence is unknown.

Spondyloperipheral dysplasia is caused by variants (also called mutations) in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found in the clear gel that fills the eyeball (the vitreous) and in cartilage. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development; most cartilage is later converted to bone. Type II collagen is essential for the normal growth and development of bones and other connective tissues.

The variants in the COL2A1 gene that cause spondyloperipheral dysplasia typically affect a region of the protein called the C-propeptide domain. These variants cause cells to produce an abnormal version of the COL2A1 protein, which interferes with the production of mature type II collagen molecules. A reduction in the amount of mature type II collagen in the body disrupts the normal development of bones and other connective tissues, leading to the skeletal abnormalities seen in people with spondyloperipheral dysplasia.

Genetic Testing Information

• Genetic Testing Registry: Spondyloperipheral dysplasia

Genetic and Rare Diseases Information Center

• Spondyloperipheral dysplasia-short ulna syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• SPONDYLOPERIPHERAL DYSPLASIA

Scientific Articles on PubMed

• PubMed

• Barat-Houari M, Sarrabay G, Gatinois V, Fabre A, Dumont B, Genevieve D, Touitou I. Mutation Update for COL2A1 Gene Variants Associated with Type II Collagenopathies. Hum Mutat. 2016 Jan;37(1):7-15. doi: 10.1002/humu.22915. Epub 2015 Oct 21. Citation on PubMed
• Bedeschi MF, Bianchi V, Gentilin B, Colombo L, Natacci F, Giglio S, Andreucci E, Trespidi L, Acaia B, Furga AS, Lalatta F. Prenatal manifestation and management of a mother and child affected by spondyloperipheral dysplasia with a C-propeptide mutation in COL2A1: case report. Orphanet J Rare Dis. 2011 Feb 28;6:7. doi: 10.1186/1750-1172-6-7. Citation on PubMed
• Desir J, Cassart M, Donner C, Coucke P, Abramowicz M, Mortier G. Spondyloperipheral dysplasia as the mosaic form of platyspondylic lethal skeletal dyplasia torrance type in mother and fetus with the same COL2A1 mutation. Am J Med Genet A. 2012 Aug;158A(8):1948-52. doi: 10.1002/ajmg.a.35301. Epub 2012 Apr 11. Citation on PubMed
• Gregersen PA, Savarirayan R. Type II Collagen Disorders Overview. 2019 Apr 25 [updated 2024 Oct 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK540447/ Citation on PubMed
• Unger S, Ferreira CR, Mortier GR, Ali H, Bertola DR, Calder A, Cohn DH, Cormier-Daire V, Girisha KM, Hall C, Krakow D, Makitie O, Mundlos S, Nishimura G, Robertson SP, Savarirayan R, Sillence D, Simon M, Sutton VR, Warman ML, Superti-Furga A. Nosology of genetic skeletal disorders: 2023 revision. Am J Med Genet A. 2023 May;191(5):1164-1209. doi: 10.1002/ajmg.a.63132. Epub 2023 Feb 13. Citation on PubMed
• Zabel B, Hilbert K, Stoss H, Superti-Furga A, Spranger J, Winterpacht A. A specific collagen type II gene (COL2A1) mutation presenting as spondyloperipheral dysplasia. Am J Med Genet. 1996 May 3;63(1):123-8. doi: 10.1002/(SICI)1096-8628(19960503)63:13.0.CO;2-P. Citation on PubMed
• Zankl A, Neumann L, Ignatius J, Nikkels P, Schrander-Stumpel C, Mortier G, Omran H, Wright M, Hilbert K, Bonafe L, Spranger J, Zabel B, Superti-Furga A. Dominant negative mutations in the C-propeptide of COL2A1 cause platyspondylic lethal skeletal dysplasia, torrance type, and define a novel subfamily within the type 2 collagenopathies. Am J Med Genet A. 2005 Feb 15;133A(1):61-7. doi: 10.1002/ajmg.a.30531. Citation on PubMed
• Zankl A, Zabel B, Hilbert K, Wildhardt G, Cuenot S, Xavier B, Ha-Vinh R, Bonafe L, Spranger J, Superti-Furga A. Spondyloperipheral dysplasia is caused by truncating mutations in the C-propeptide of COL2A1. Am J Med Genet A. 2004 Aug 30;129A(2):144-8. doi: 10.1002/ajmg.a.30222. Citation on PubMed