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HSPG2 gene

Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

HSPG2 gene

The HSPG2 gene provides instructions for making the protein perlecan, which is essential for the structure and function of basement membranes and cartilage.

Normal Function

The HSPG2 gene provides instructions for making a protein called perlecan. This protein is found in the extracellular matrix, the intricate lattice of proteins and other molecules that forms in the spaces between cells. Specifically, it is found in the basement membrane, a thin, sheet-like structure that separates and supports cells in many tissues. Perlecan is also found in cartilage, the tough, flexible tissue that makes up much of the skeleton during early development.

Perlecan is a heparan sulfate proteoglycan, a type of protein that interacts with many other molecules to perform various functions, including:

  • Cell signaling
  • Cell adhesion (the sticking of cells to one another)
  • Angiogenesis (the formation of new blood vessels)
  • Maintenance of basement membranes and cartilage throughout life
  • Relaying signals at the neuromuscular junction to trigger muscle contraction

Health Conditions Related to Genetic Changes

Schwartz-Jampel syndrome

More than 30 mutations in the HSPG2 gene have been found to cause Schwartz-Jampel syndrome. This rare condition is characterized by continuous muscle contraction (myotonia) that restricts movement, as well as bone abnormalities known as chondrodysplasia.

Most of these mutations reduce the amount of perlecan produced or result in a partially functional version of the protein. This deficiency disrupts the development of cartilage and bone tissue. Additionally, a reduced amount of functional perlecan at the neuromuscular junction alters the balance of signaling molecules, leading to continuous muscle contraction.

Other disorders

Mutations in the HSPG2 gene can also cause a severe form of chondrodysplasia called dyssegmental dysplasia, Silverman-Handmaker type. These mutations prevent the production or transport of any functional perlecan. A total lack of this protein significantly disrupts the development of cartilage and bone, and most affected individuals die before birth, are stillborn, or live only into early infancy.

Other Names for This Gene

  • endorepellin (domain V region)
  • perlecan
  • perlecan proteoglycan
  • PLC
  • PRCAN

Frequently Asked Questions

Schwartz‑Jampel syndrome caused by HSPG2 mutations follows an autosomal recessive pattern. Both parents must carry one pathogenic copy of the gene. If you are affected (having two mutated copies), each of your children will inherit one mutated copy from you and will be a carrier unless the other parent also carries a pathogenic HSPG2 variant. If the other parent is a carrier, there is a 50 % chance each child will have the syndrome and a 50 % chance they will be a carrier. Genetic counseling and carrier testing for the partner are recommended before family planning.
Urgent evaluation is needed if the infant shows severe skeletal abnormalities such as markedly short limbs, abnormal vertebral segmentation, or chest wall deformities that compromise breathing. Additional red‑flags include respiratory distress, failure to thrive, or signs of neuromuscular weakness. Early referral to a pediatric geneticist and orthopedic specialist can guide supportive care and inform prognosis.
Yes, tailored physical therapy focusing on gentle stretching, range‑of‑motion exercises, and low‑impact strengthening can help reduce stiffness and maintain joint flexibility. Orthopedic interventions such as tendon releases or corrective osteotomies may be considered for severe contractures, but they are usually adjuncts to ongoing therapy. Treatment plans should be individualized and coordinated with a neurologist familiar with the syndrome.
Currently, no therapy directly restores perlecan function. Management is supportive: regular monitoring of growth, orthopedic surveillance for deformities, and surgical correction when needed. Experimental approaches, such as gene‑replacement or perlecan‑mimetic molecules, are under investigation but are not yet available clinically. Participation in clinical trials may be an option for eligible patients.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.