Kyphoscoliotic Ehlers-Danlos Syndrome (kEDS)

kEDS is a genetic connective tissue disorder that causes kyphoscoliosis, muscle hypotonia, and joint hypermobility.

kEDS is an ultra-rare disorder that affects less than 1 in 1 million people.

kEDS is caused by differences in the genes called genetic variants. These genetic variants affect the connective tissue, which provides support, protection, and structure throughout the body.

kEDS is caused by genetic variants of these genes:

• PLOD1 
• FKBP14 

kEDS is inherited in an autosomal recessive pattern. This means if a person inherits the genetic variant from both of their parents, they will have kEDS. People with one copy of the genetic variant are carriers of kEDS. Carriers do not have the condition themselves but may pass the genetic variant on to their children.

PLOD1 and FKBP14 variants are each associated with a different set of symptoms, but variants of both genes are associated with:

• Congenital or early-onset kyphoscoliosis
• Muscle hypotonia (low muscle tone)
• Joint hypermobility
• Delayed motor development
• Issues with the eyes (including bluish sclerae and refractive errors)
• Foot deformities (including clubfoot and flat feet)
• Soft, stretchy skin
• Easy bruising

People with PLOD1-kEDS may also have:

• Joint instability
• Skin fragility
• Atrophic scarring
• Ocular fragility

People with FKBP14-kEDS may also have:

• Congenital hearing loss
• Muscle atrophy

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 criterion 1 AND major criterion 2 AND major criterion 3

OR

Major criterion 1 AND major criterion 2 AND three minor criteria (general or gene-specific)

Major Criteria 

1. Congenital muscle hypotonia
2. Congenital or early onset kyphoscoliosis (progressive or non-progressive)
3. Generalized joint hypermobility with dislocations/subluxations (shoulders, hips, and knees in particular)

Minor Criteria

1. Skin hyperextensibility
2. Easy bruisable skin
3. Rupture/aneurysm of a medium-sized artery
4. Osteopenia/osteoporosis
5. Blue sclerae
6. Hernia (umbilical or inguinal)
7. Pectus deformity
8. Marfanoid habitus
9. Talipes equinovarus
10. Refractive errors (myopia, hypermetropia)

Gene-Specific Minor Criteria 

PLOD1 

1. Skin fragility (easy bruising, friable skin, poor wound healing, widened atrophic scarring)
2. Scleral and ocular fragility/rupture
3. Microcornea
4. Facial dysmorphology

FKBP14 

1. Congenital hearing impairment (sensorineural, conductive, or mixed)
2. Follicular hyperkeratosis
3. Muscle atrophy
4. Bladder diverticula

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 individual needs.

Resources

The Ehlers-Danlos Syndromes, Rare Types 

PLOD1-Related Kyphoscoliotic Ehlers-Danlos Syndrome 

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 

 Mutations in FKBP14 Cause a Variant of Ehlers-Danlos Syndrome with Progressive Kyphoscoliosis, Myopathy, and Hearing Loss 

The 2017 International Classification of the Ehlers-Danlos Syndromes