Day: December 5, 2022

What is the Current Classification for Ehlers-Danlos Syndrome?

Patient Presentation
A 4-year-old female came to clinic for her health supervision visit. Her mother had no complaints except that she was concerned that the child may have Ehlers-Danlos syndrome. “I’m being evaluated now because I’ve always been double-jointed and had some pain now and then. But during my last pregnancy with her brother I had a lot of problems and my doctor is starting to evaluate me more. She complains once in a while about her legs being tired, so it just makes me worried,” the mother explained.

The past medical history was positive for admission for respiratory syncytial virus and 2 otitis media diagnoses. The review of systems was negative for other problems such specific joint pain, problems moving after resting for time, easy bruisability or skin problems, being “double-jointed”, true fatigue, problems playing or keeping up with other children, abnormal muscle strength or dental problems. Her mother also said that she complained of the leg pain after playing for a long period of time and was better after resting. It occurred infrequently.

The pertinent physical exam showed a smiling female with growth parameters in the 25% and was proportional. Her physical examination was normal. Her Beighton score was 3 for bilateral dorsiflexing her 5th metacarpal to 90%, and she could place her hands on the floor with forward flexion of the trunk.

The diagnosis of a healthy female was made. The pediatrician felt that the intermittent leg discomfort was most likely due to exercise but asked the mother to monitor it. She also recommended that the mother let her know about the outcome of the mother’s evaluation. “Depending on if your doctor finds any problems and what type of problems they are, we may need to do something for her and her brother but we’ll see what you find out,” she recommended.

Discussion
As with any potential problem there is a often a range from normal to abnormal and this is true for joint hypermobility. Generalized joint hypermobility is hypermobility in multiple joints with few or no other symptoms. Generalized hypermobility spectrum disorder (also known as joint hypermobility syndrome) has hypermobility along with other symptoms such as pain, reduced muscle strength, and decreased proprioception and balance. Other clinical entities with hypermobility include Ehlers-Danlos syndrome, Marfan syndrome, and osteogenesis imperfecta.

In the office, a 5-point questionnaire with 2 or more “yes” answers has high sensitivity (80-85%) and specificity (89-90%) for joint hypermobility. It includes:

“1. Can you now (or could you ever) place your hands flat on the floor without bending your knees?
2. Can you now (or could you ever) bend your thumb to touch your forearm?
3. As a child, did you amuse your friends by contorting your body into strange shapes
or could you do the splits?
4. As a child or teenager, did your shoulder or kneecap dislocate on more than one
occasion?
5. Do you consider yourself “double-jointed”?””

The most commonly recognized scoring system for joint hypermobility on physical examination is the Beighton score which can be reviewed here. Children have more joint mobility therefore they have a higher cutoff score than adults (Beighton score = 5-6 versus adults with score of 4-5).

Learning Point
Although recognized since ancient times, Ehlers-Danlos syndrome (EDS) was first named in 1936 after Ehlers and Danlos who were both dermatologists. EDS is a genetic connective tissue disorder with heterogeneous clinical characteristics that include joint hypermobility, tissue fragility and skin hyperextensibility. Because of newer genetic research and testing and increased recognition of the problems, several classification systems for EDS have evolved over the past 40 years. As this involves soft tissue or related structures, it is not surprising that EDS has various clinical patterns. The most recent international classification includes 13 different patterns which are:

  • Classic
  • Abbreviation: cEDS
  • Genetic Pattern: Autosomal Dominant
  • Major criteria are skin hyperextensibility and aulophic scarring, and generalized joint hypermobility
  • Classic-like
  • Abbreviation: cIEDS
  • Genetic Pattern: Autosomal Recessive
  • Major criteria are skin hyperextensibility and aulophic scarring, and generalized joint hypermobility, and easy bruisability skin / spontaneous ecchymoses
  • Hypermobile
  • Abbreviation: hEDS
  • Genetic Pattern: Autosomal Dominant
  • Is a clinical diagnosis with major criteria being generalized joint hypermobility, several criterion and features within the criterion. These include various skin, joint, soft tissue, vascular and other features and also genetic risk
  • Cardio-valvular
  • Abbreviation: cvEDS
  • Genetic Pattern: Autosomal Dominant
  • Major criteria are progressive cardiac-vascular problems, skin involvement and joint hypermobility
  • Vascular
  • Abbreviation: vEDS
  • Genetic Pattern: Autosomal Dominant
  • Major criteria are family history of vEDS, arterial rupture, spontaneous sigmoid colon perforation, uterine rupture, carotid-cavernous sinus fistula
  • Arulochalasia
  • Abbreviation: aEDS
  • Genetic Pattern: Autosomal Dominant
  • Dermatosparaxis
  • Abbreviation: dEDS
  • Genetic Pattern: Autosomal Recessive
  • Kyphoscoliotic
  • Abbreviation: kEDS
  • Genetic Pattern: Autosomal Recessive
  • Brittle Cornea syndrome
  • Abbreviation: BEDS
  • Genetic Pattern: Autosomal Recessive
  • Spondylodysplastic
  • Abbreviation: spEDS
  • Genetic Pattern: Autosomal Recessive
  • Musculoconulactural
  • Abbreviation: mcIEDS
  • Genetic Pattern: Autosomal Recessive
  • Myopathic
  • Abbreviation: mIEDS
  • Genetic Pattern: Autosomal Dominant or Autosomal Recessive
  • Periodontal
  • Abbreviation: pIEDS
  • Genetic Pattern: Autosomal Dominant

Questions for Further Discussion
1. What is included in the differential diagnosis of joint pain? A review can be found here
2. What are indications for referral to genetics, rheumatology or orthopaedics for potential hypermobility?
3. What are treatments for hypermobility with associated musculoskeletal problems?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Ehlers-Danlos Syndrome and Connective Tissue Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Baeza-Velasco C, Grahame R, Bravo JF. A connective tissue disorder may underlie ESSENCE problems in childhood. Research in Developmental Disabilities. 2017;60:232-242. doi:10.1016/j.ridd.2016.10.011

Scheper MC, Juul-Kristensen B, Rombaut L, Rameckers EA, Verbunt J, Engelbert RH. Disability in Adolescents and Adults Diagnosed With Hypermobility-Related Disorders: A Meta-Analysis. Arch Phys Med Rehabil. 2016;97(12):2174-2187. doi:10.1016/j.apmr.2016.02.015

Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 2017;175(1):8-26. doi:10.1002/ajmg.c.31552

van Meulenbroek T, Huijnen IPJ, Simons LE, Conijn AEA, Engelbert RHH, Verbunt JA. Exploring the underlying mechanism of pain-related disability in hypermobile adolescents with chronic musculoskeletal pain. Scand J Pain. 2021;21(1):22-31. doi:10.1515/sjpain-2020-0023

Ehlers-Danlos syndrome. Accessed October 10, 2022. http://www.whonamedit.com/synd.cfm/2017.html

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa