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Ehlers-Danlos syndrome

Ehlers-Danlos syndrome


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High Yield Notes
6 pages

Ehlers-Danlos syndrome

12 flashcards

USMLE® Step 1 style questions USMLE

1 questions

A 20-year-old woman comes to the emergency room because of a possible elbow dislocation. The patient was playing on the playground with her nephew when she tripped and fell onto her outstretched right arm. She has had multiple joint dislocations since childhood, including both elbow joints. The patient has also experienced easy bruising and poor wound healing following minor cuts. Family history is significant for similar symptoms in the patient’s father. Her height is 157 cm and weight is 56 kg (123.4 lb). Vitals are within normal limits. Physical examination shows several wide atrophic scars on the upper and lower extremities. There is a prominent right olecranon, and the right forearm appears foreshortened. Sensation is intact, though strength testing is limited due to pain. Radial pulses are present bilaterally. Skin and joint examination are shown below:

Image reproduced from Wikimedia Commons

Which of the following is most likely responsible for this patient’s presentation?

External References

Content Reviewers:

Rishi Desai, MD, MPH

Ehlers-Danlos syndrome is a group of related genetic conditions that are all caused by defective collagen synthesis. Normally, collagen provides strength and elasticity to our bodies, and it's found in the skin, ligaments, tendons, and bones. In Ehlers-Danlos syndrome, defective collagen leads to stretchy skin, easy bruising, and joints that are super flexible.

Now, the cells that produce collagen are fibroblasts, and they make five types of collagen. These five types have specific parts of the body they call home. Type I collagen makes its home in the skin, tendons, organs, and bones. Type II collagen makes its home in the cartilage. Type III collagen, in reticular fibers, form a supporting mesh for soft organs like the liver and blood vessels. Type IV collagen is found in a foundation called the basal lamina, on which the epithelial cells sit. Finally, there’s type V collagen which is in cell surfaces, hair, and placenta, as well as in places where type I collagen is found.

The synthesis of collagen, like any other protein, starts with the genes. The name of the genes that encode for a collagen type usually starts with the prefix COL, followed by the collagen number type, and the pro-alpha-chain it encodes. There are many genes that encode for the different types of collagen, like COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2. Let’s take the genes COL5A1 and COL5A2 that encode for type V collagen as an example. In COL5A1, COL stands for collagen. The five stands for type V collagen and the A1 refers to an alpha-1-chain. So, COL5A1 encodes a collagen type V alpha-1-chain. Now, to synthesize type V collagen, for example. COL5A1 and COL5A2 get transcribed from DNA to mRNA and then get translated from mRNA into a string of amino acids that make up a protein. This process happens many times over. Now, this string of amino acids consists mostly of glycine and two other random amino acids, usually, proline and lysine that repeat over and over as amino acid triplets.

Ultimately, this peptide forms what is called preprocollagen which can be a collagen type V alpha-1-chain or a collagen type V alpha-2-chain depending on the gene that encodes the protein. Next, preprocollagen undergoes hydroxylation which is where two enzymes called prolyl hydroxylase and lysyl hydroxylase, with the help of many cofactors like vitamin C, add hydroxyl groups onto proline and lysine.

Then there’s a process called glycosylation, which is done by two enzymes, galactosyl, and glucosyltransferase which add glucose or galactose monomers onto the hydroxyl groups. After that, three of these chains twist into a triple helix called procollagen. Now, two combinations can make up the helix or procollagen for type V collagen, three type V alpha-1-chains or two type V alpha-1-chains and one type V alpha-2-chain. The procollagen is then put in a vesicle by the Golgi apparatus and sent off into the extracellular space.

In the extracellular space, procollagen undergoes proteolytic processing. That’s where a tiny band of enzymes called collagen peptidases cleave the loose strands at both ends of the procollagen protein, turning procollagen into tropocollagen. At this stage, tropocollagen is the mature type V collagen. Finally, there’s a stage called cross-linking, which is where lots of tropocollagen molecules, in this case, type V collagen, bind together with the help of a copper-dependent enzyme called lysyl oxidase to form a stack of collagen fibrils with Type I collagen.

Now, the cause of Ehlers-Danlos syndrome is typically due to a mutation on a gene that encodes for a type of collagen protein. The name of the gene that encodes for collagen usually starts with the prefix COL. The specific gene involved determines the type of Ehlers-Danlos syndrome. So for example, classical Ehlers-Danlos syndrome or cEDs for short is caused by mutations in the COL5A1 and COL5A2 collagen V genes. These genes are passed through autosomal dominant inheritance where only one mutant allele is needed for the disease.

Vascular Ehlers-Danlos syndrome or vEDs is caused by a mutation in the COL3A1 gene which causes a decrease in Type III collagen synthesis which weakens blood vessels.


Ehlers-Danlos syndrome (EDS) is a genetic connective tissue disorder that affects the synthesis of collagen. EDS is classically characterized by hyperextensible skin, hypermobile joints, and easy bruising and bleeding. It can sometimes present with aneurysms, or vascular dissections which can all lead to catastrophic vascular rupture.

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