Kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is a heritable connective tissue disorder that causes low muscle tone, early-onset kyphoscoliosis, and joint hypermobility. People with kEDS also have an increased risk of life-threatening arterial dissection and rupture.
kEDS is an ultra-rare disorder that affects less than 1 in 1 million people.
Key signs and symptoms of kEDS include:
You can learn more about the features of kEDS by selecting different body parts from the menu.
Genetic Basis
kEDS is caused by genetic variants in these genes:
Humans have two copies of each gene because we inherit one from each parent. People with kEDS typically have pathogenic variants in both copies of the PLOD1 or FKBP14 gene.
Inheritance
kEDS is inherited in an autosomal recessive pattern. Autosomal means it can be passed on and inherited equally by males and females. Recessive means the condition only occurs when both copies of a gene are affected by pathogenic variants.
People with kEDS will always pass on one pathogenic variant to their children. Their children will only have kEDS if they inherit a second pathogenic variant in the same gene from their other parent.
People with one recessive pathogenic variant are known as carriers. Carriers do not have kEDS themselves but may pass the genetic variant on to their children.
If a person meets the diagnostic criteria for kEDS, genetic testing should be done to confirm the diagnosis. Genetic testing is used to see if a person has the genetic variants that cause kEDS.
To meet the diagnostic criteria for kEDS, a person must meet:
Major Criteria
Minor Criteria
Gene-Specific Minor Criteria
PLOD1
FKBP14
kEDS is managed by addressing the symptoms a person is experiencing. kEDS can cause a variety of symptoms in many different areas of the body, so people with kEDS may require multiple providers in different specialties to manage their care. Key aspects of care focus on the musculoskeletal system, skin, and cardiovascular system. Each person should work with their care team to develop a care plan that meets their needs.
Signs and Symptoms
Musculoskeletal
Cardiovascular
Chest and lungs
Skin
Gastrointestinal
Pelvic Organs
Eyes
Ears
Hands
Feet
Pregnancy
How to Use:
Explore the features of kEDS by selecting different body parts from the menu.
Please note that kEDS affects each person differently. The symptoms listed here may not affect everyone with kEDS, and people with kEDS may have other symptoms that are not listed on this page. This page is intended to provide information about symptoms that may occur in individuals with kEDS and does not constitute medical advice. Always consult a healthcare professional for personalized medical guidance.
Select from the list below to learn how kEDS can affect the musculoskeletal system.
Kyphoscoliosis is a combination of two spinal conditions: kyphosis and scoliosis. Kyphosis is an abnormal forward curve in the spine that causes the upper back to look more rounded. Scoliosis is a sideways curve in the spine that gives the spine an “S” or “C” shape.
Kyphoscoliosis is often present at birth in people with kEDS but may also develop in early childhood. It is usually severe and progressive in kEDS.
Joint hypermobility means a joint has a greater range of motion than usual. People with kEDS often have generalized joint hypermobility, which means joint hypermobility is present in many areas throughout the body.
A joint is the point where two or more bones connect. Joint instability means the bones of a joint are not held together securely. This can lead to joint subluxations, dislocations, sprains, and other injuries.
A joint dislocation occurs when two bones at a joint separate completely and are no longer touching. A subluxation is a partial dislocation in which two bones at a joint are out of place but are still touching each other.
Muscle tone is the amount of tension (or resistance to movement) in the muscles. Muscle tone allows us to hold our bodies upright and affects the control, speed, and range of our movement. Muscle hypotonia, or low muscle tone, means the muscles are floppy and unable to properly support the body’s position and movement. It may require more effort for people with hypotonia to move and maintain good posture.
Low muscle tone is often observed at birth (known as floppy infant) in kEDS and may result in children taking longer to learn to walk.
Muscle atrophy is the thinning of muscle tissue, also called muscle wasting.
🧬 Muscle atrophy is seen in some people with kEDS who have pathogenic variants in the FKBP14 gene.
Motor skills are actions that use specific muscle movements to perform a particular task. Delayed gross motor development means that a child has trouble with motor skills that other children their age can do.
Gross motor skills are tasks that involve large muscle groups, such as rolling, crawling, and walking. It may take children with kEDS longer to learn to walk, but most children can eventually walk independently.
Bone density is the amount of minerals in the bones. Bones that contain more minerals are denser and stronger. Bones with less minerals are weaker and may be more vulnerable to fractures.
Congenital hip dysplasia, also called congenital hip dislocation, is a condition in which the hip joint is not formed correctly at birth. The hip is a ball-and-socket joint. The ball of the femur moves within the socket of the pelvis, allowing movement of the legs. In someone with hip dysplasia, the socket of the pelvis is too shallow to support the ball of the femur properly. This can lead to instability, pain, and problems with walking. Congenital hip dysplasia is sometimes seen in kEDS but is not considered a common feature.
A joint contracture is a fixed tightening of tissues that prevents normal joint movement. People with kEDS are sometimes born with joint contractures of the fingers, wrists, elbows, or knees.
Select from the list below to learn how kEDS can affect the cardiovascular system.
Arteries are tubes that carry blood from the heart to the rest of the body. An arterial aneurysm is a bulge or swelling in the wall of an artery. Aneurysms occur when blood flow puts pressure on a weak spot in the blood vessel wall and causes it to swell. If an aneurysm swells too much, it can rupture (burst), which is a life-threatening medical emergency.
kEDS can cause aneurysms of both major and minor arteries, including the aorta, which is the largest artery in the body. An aneurysm of the aorta is called an aortic aneurysm.
An arterial dissection is a tear in the inner wall of an artery. Blood from the artery flows into the tear and separates the layers of the artery wall, creating a weak spot that may lead to a life-threatening leak.
kEDS can cause dissection of both major and minor arteries, including the aorta. A dissection of the aorta is called an aortic dissection.
⚠️ An arterial dissection can be life-threatening and should be treated as a medical emergency.
Arterial rupture is a complete tear through the artery wall that creates a hole and allows blood to leak out of the artery. kEDS can cause rupture of both major and minor arteries, including the aorta. A rupture of the aorta is called an aortic rupture.
⚠️ An arterial rupture can be life-threatening and should be treated as a medical emergency.
Select from the list below to learn how kEDS can affect the chest and lungs.
Pectus excavatum is an indentation in the chest that occurs when the sternum grows inward. This happens when too much connective tissue grows between the ribs and the sternum. Mild pectus excavatum may not cause any problems, but if the indentation is deep enough, it can put pressure on the lungs and heart.
Pectus carinatum is a bump on the chest that occurs when the sternum sticks outward more than usual. This happens when too much connective tissue grows between the ribs and sternum. Pectus carinatum does not usually cause symptoms but can cause shortness of breath when exercising. Pectus excavatum is more common than pectus carinatum in kEDS.
Select from the list below to learn how kEDS can affect the skin.
Skin hyperextensibility means the skin can be stretched beyond the normal range.
Some people with kEDS have unusual skin characteristics. Their skin may be thin, soft, velvety, or doughy to the touch.
People with kEDS may have fragile skin that is prone to tearing.
People with kEDS often bruise very easily because the blood vessels near the skin surface are more fragile and more easily damaged.
Wounds may heal more slowly than usual in people with kEDS.
Atrophic scars are scars that have widened and become thin, causing them to appear sunken.
Follicular hyperkeratosis is a condition that causes thick, rough bumps on the skin. The bumps are the result of excess keratin around the hair follicles.
🧬 Follicular hyperkeratosis is reported in people with kEDS who have pathogenic variants in the FKBP14 gene.
Select from the list below to learn how kEDS can affect the gastrointestinal system.
A hernia occurs when an internal organ pushes through a weak spot in the tissues that support it, creating an outward bulge. kEDS is associated with umbilical hernias (near the bellybutton) and inguinal hernias (in the groin).
Select from the list below to learn how kEDS can affect the pelvic organs.
A bladder diverticulum (plural: diverticula) occurs when the bladder lining pushes through a weak spot in the bladder wall. This creates a pouch that sticks out from the bladder. Bladder diverticula do not always cause symptoms, but large bladder diverticula may cause bladder stones, urinary tract infections, and other urinary problems.
🧬 Large bladder diverticula have been reported in people with kEDS who have pathogenic variants in the FKBP14 gene.
Select from the list below to learn how kEDS can affect the eyes.
The sclera (plural: sclerae) is a protective layer of connective tissue that surrounds most of the eye. The sclera is usually white but is more transparent when collagen fibers are thin. This allows the underlying tissue to show through, giving the eyes a bluish color.
The cornea is a clear protective dome that covers the iris and the pupil and allows light to enter the eye. Microcornea refers to a cornea that is smaller than usual, with a diameter of less than 10 mm. Microcornea may cause problems with vision.
Myopia, also called nearsightedness or shortsightedness, is a condition that makes it difficult to see objects that are far away. Due to differences in eye shape, people with myopia can see objects near them more clearly but have trouble seeing objects further away.
A globe rupture is a tear in the outer layer of the eye. In people with kEDS, a globe rupture may occur spontaneously with no apparent cause or trauma.
⚠️ A globe rupture is a medical emergency. Rapid medical treatment is required to preserve vision.
Select from the list below to learn how kEDS can affect the ears.
🧬 Hearing impairment is reported in people with kEDS who have pathogenic variants in the FKBP14 gene. Hearing loss may be sensorineural, conductive, or mixed.
Sensorineural hearing loss occurs when there is a problem with the inner ear or the auditory nerve that delivers sound to the brain.
Conductive hearing loss occurs when sound can’t reach the inner ear due to blockage, structural problems, or damage in the outer or middle ear.
Mixed hearing loss is a combination of sensorineural and conductive hearing loss.
Select from the list below to learn how kEDS can affect the hands.
Some people with kEDS have arachnodactyly, which means their fingers and toes are unusually long and slender.
Select from the list below to learn how kEDS can affect the feet.
Flat feet (pes planus) means the feet have little to no arch when standing. When a person with flat feet stands, the entire bottom of their foot touches the ground.
Clubfoot (talipes equinovarus) causes the foot to point downward and twist inward. This causes the toes to point toward the opposite leg and can make walking difficult if not addressed.
Select from the list below to learn how kEDS can affect pregnancy.
Reduced fetal movements mean the fetus does not move around as much during pregnancy. This is sometimes reported when the fetus has kEDS.
Premature rupture of membranes (PROM) means that the amniotic sac breaks open before labor begins. The amniotic sac, also called the membranes, is filled with amniotic fluid and surrounds the fetus during pregnancy. When the amniotic sac breaks open, amniotic fluid leaks out. This is commonly referred to as the water breaking.
When the amniotic sac breaks open before the 37th week of pregnancy, it is called preterm premature rupture of membranes (PPROM). Once the amniotic sac breaks, there is an increased risk of premature birth and infection.
A brain hemorrhage is bleeding in the brain. An antenatal hemorrhage is bleeding in a fetus’s brain before birth. A neonatal brain hemorrhage is bleeding in a baby’s brain after birth, during the first month of life. Antenatal and neonatal brain hemorrhage are sometimes reported when the baby has kEDS.
Please note that kEDS affects each person differently. The symptoms listed here may not affect everyone with kEDS, and people with kEDS may have other symptoms that are not listed on this page. This page is intended to provide information about symptoms that may occur in individuals with kEDS and does not constitute medical advice. Always consult a healthcare professional for personalized medical guidance.
The Ehlers-Danlos Syndromes, Rare Types (Brady et al., 2017)
https://doi.org/10.1002/ajmg.c.31550
The 2017 International Classification of the Ehlers-Danlos Syndromes (Malfait et al., 2017)
https://doi.org/10.1002/ajmg.c.31552
PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome (Yeowell et al., 2018)
https://www.ncbi.nlm.nih.gov/books/NBK1462/
A cohort of 17 patients with kyphoscoliotic Ehlers–Danlos syndrome caused by biallelic mutations in FKBP14: expansion of the clinical and mutational spectrum and description of the natural history (Giunta et al., 2018)
https://doi.org/10.1038/gim.2017.70
Mutations in FKBP14 Cause a Variant of Ehlers-Danlos Syndrome with Progressive Kyphoscoliosis, Myopathy, and Hearing Loss (Baumann et al., 2012)
https://doi.org/10.1016/j.ajhg.2011.12.004
