Spondylodysplastic Ehlers-Danlos Syndrome (spEDS)

spEDS is a genetic connective tissue disorder that causes short stature, muscle hypotonia, joint hypermobility, and joint contractures. spEDS also causes skin hyperextensibility, characteristic craniofacial features, and developmental delays.

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

spEDS 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.

spEDS is caused by genetic variants of these genes:

• B4GALT7 
• B3GALT6 
• SLC39A13 

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

Variants of B4GALT7, B3GALT6, and SLC39A13 are each associated with a different set of symptoms, but variants of all three genes are associated with:

• Short stature
• Muscle hypotonia (low muscle tone)
• Joint hypermobility
• Joint contractures
• Skin hyperextensibility
• Atrophic scarring

People with B3GALT6-spEDS may also have:

• Characteristic craniofacial features
  • Midfacial hypoplasia
  • Prominent forehead
  • Prominent eyes or proptosis
  • Blue sclerae
  • Down-slanting palpebral fissures
  • Depressed nasal bridge
  • Long upper lip
  • Low-set ears
  • Micrognathia
  • Abnormal dentition
  • Cleft palate
  • Sparse hair
• Characteristic radiographic findings
  • Platyspondyly
  • Anterior beak of vertebral body
  • Short ilium
  • Prominent lesser trochanter
  • Acetabular dysplasia
  • Metaphyseal flaring
  • Metaphyseal dysplasia of femoral head
  • Elbow malalignment
  • Radial head dislocation
  • Overtubulation
  • Bowing of long bones
  • Generalized osteoporosis
  • Healed fractures
• Kyphoscoliosis
• Osteoporosis with multiple fractures
• Joint dislocations
• Slender, tapering fingers
• Delayed motor development
• Mild to moderate cognitive delay

If a person meets the diagnostic criteria for spEDS, genetic testing should be done to confirm the diagnosis. Genetic testing is used to see if a person has the genetic variants that cause spEDS.

To meet the diagnostic criteria for spEDS, a person must meet major criterion 1 AND major criterion 2 AND have characteristic radiographic abnormalities AND at least two other minor criteria (general or gene-specific)

Major Criteria 

1. Short stature (progressive in childhood)
2. Muscle hypotonia (ranging from severe congenital to mild later onset)
3. Bowing of limbs

Minor Criteria

1. Skin hyperextensibility, soft, doughy skin, thin translucent skin
2. Pes planus
3. Delayed motor development
4. Osteopenia
5. Delayed cognitive development

Gene-Specific Minor Criteria 

B3GALT6 

1. Kyphoscoliosis (congenital or early onset, progressive)
2. Joint hypermobility (generalized or restricted to distal joints, with joint dislocations)
3. Joint contractures (congenital or progressive) (especially hands)
4. Peculiar fingers (slender, tapered, arachnodactyly, spatulate, with broad distal phalanges)
5. Talipes equinovarus
6. Characteristic craniofacial features
7. Tooth discoloration, dysplastic teeth
8. Characteristic radiographic findings
9. Osteoporosis with multiple spontaneous fractures
10. Ascending aortic aneurysm
11. Lung hypoplasia, restrictive lung disease

B4GALT7 

1. Radioulnar synostosis
2. Bilateral elbow contractures or limited elbow movement
3. Generalized joint hypermobility
4. Single transverse palmar crease
5. Characteristic craniofacial features
6. Characteristic radiographic findings
7. Severe hypermetropia
8. Clouded cornea

SLC39A13

1. Protuberant eyes with bluish sclerae
2. Hands with finely wrinkled palms
3. Atrophy of the thenar muscles, and tapering fingers
4. Hypermobility of distal joints
5. Characteristic radiologic findings

spEDS is managed by addressing the symptoms a person is experiencing. spEDS can cause a variety of symptoms in many different areas of the body, so people with spEDS may require multiple providers in different specialties to manage their care. Key aspects of care include physical therapy and monitoring for bone density and cardiovascular issues. Everyone with spEDS is different, so 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 

The 2017 International Classification of the Ehlers-Danlos Syndromes