Ehlers-Danlos syndrome (EDS) is the name given to a group of disorders that are caused by mutations in genes that encode for collagen or collagen-associated proteins, leading to defects in the connective tissues that give support to joints, skin, blood vessels, and other tissues and organs.

Spondylodysplastic EDS (spEDS) is one of the 13 types of EDS. The two major characteristic features of spEDS are short stature and weak muscle tone.

What causes spEDS?

spEDS is caused by mutations in the B4GALT7, B3GALT6, or SLC39A13 genes. B4GALT7 and B3GALT6 encode for proteins that add galactose (a type of sugar molecule) to the sugar chains that make up connective tissue-related proteins called proteoglycans. The end result of mutations in these two genes is the production of abnormal proteoglycan proteins, and connective tissue that lacks proper structure and sufficient strength.

SLC39A13 encodes for a protein called ZIP13, which regulates the uptake of zinc ions from the extracellular space into the cells. Zinc is required for the normal working of several proteins, including those that add hydroxyl (OH) groups to the lysine and proline amino acids in the collagen proteins. (Amino acids are the building blocks of proteins). The hydroxyl groups are necessary for proteins to crosslink with other proteins in the connective tissue. As a result of defects in the ZIP13 protein, connective tissue is weak and lacks proper structure.

How is spEDS inherited?

SpEDS is inherited in an autosomal recessive manner, which means that the disease only develops if both copies of these genes, whether B4GALT7, B3GALT6, or SLC39A13, are mutated. Each mutant copy is inherited from parents who are either carriers (carry one mutant and one healthy copy of the gene) and show no symptoms of the disease, or have two mutant gene copies themselves and are also affected by spEDS.

What are the symptoms of spEDS?

The major symptomatic features of spEDS include short stature, decreased muscle tone, and bowing of limbs. Other symptoms include soft, thin and translucent skin that is hyper-extensive, flat feet, delayed motor and cognitive development, facial dysmorphisms (unusual features), hypermobile joints, osteopenia (low bone density), and bone deformities.

How is spEDS diagnosed?

spEDS is diagnosed based on physical features and the results of X-rays and genetic tests.

Genetic testing can identify mutations in the key B4GALT7, B3GALT6, and SLC39A13 genes. But it may also span other genes, mutations in which cause other types of EDS, and a considerable overlap in symptoms among these different disease types is known. Genes that can also be tested include PLOD1, FKBP14, ZNF469, PRDM5, CHST14, and DSE.

In the case of SLC39A13, urinary tests may be performed to evaluate levels of pyridinolines, lysyl‐pyridinoline (LP), and hydroxylysyl‐pyridinoline (HP), as a high LP/HP ratio is observed in spEDS patients with SLC39A13 mutations.

How is spEDS treated?

Like with other forms of EDS, there currently is no cure for spEDS. Symptomatic treatments include:

  • physiotherapy to improve muscle strength and coordination.
  • pain medications, including non-steroidal anti-inflammatory drugs (NSAIDs), to alleviate joint pain.
  • Surgery to fix joint dislocations or fractures.

 

Last updated: Nov. 3, 2019

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Ehlers-Danlos News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health providers with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.