Classical Ehlers-Danlos Syndrome

EDNF National Conference
August 15th, 2015
Classical Ehlers-Danlos
Syndrome
MARK E. LAVALLEE, M.D, C.S.C.S, F.A.C.S.M.
DIRECTOR, YORK HOSPITAL SPORTS MEDICINE FELLOWSHIP
PAST CHAIR, EDNF, PROFESSIONAL ADVISORY COUNCIL
ASS’T CLIN.PROFESSOR, PENN STATE UNIV., COLLEGE OF MEDICINE
ADJUNCT CLIN. PROFESSOR, DREXEL UNIVERSITY, SCHOOL OF MEDICINE
CHAIRMAN, USA WEIGHTLIFTING, SPORTS MEDICINE SOCIETY
TEAM PHYSICIAN, GETTYSBURG COLLEGE
YORK, PENNSYLVANIA
Disclosures
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No conflicts of interests
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No Financial disclosers to reveal
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All patients have given permission for their images/stories to be used
in this talk.
OBJECTIVES
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Molecular Genetics (as best we know it as of 2015)
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History of Ehlers-Danlos
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Define signs / symptoms of Classical Type
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Stages of Classical EDS
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Youth concerns
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Adolescent concerns
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Adult concerns
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Mature adult concerns
Pearls of the “care and well-being” of the Classical EDS Patient
What is Collagen?

Most abundant structural
protein in our bodies!

Triple Helix (i.e. rope)
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Found in bone, cartilage,
tendons, ligaments etc.

>>18 different types now
identified
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In EDS, processing
problem at cellular level
Testing for Classical Type of EDS
HISTORY & EXAM- still GOLD standard
GENETIC: Appears to be mostly on COL5A1 and COL5A2
genes. Can be tested via blood or live skin biopsy.
STRUCTURAL: electron microscopy, mostly done in
Germany, no standards set as of 2015.
Loeys-Deitz Syndrome (2005)
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A variant of Marfan? EDS?
TGFBR1 & TGFBR2
Long arms/fingers
Aortic aneuryms
Aoritc dissection/tortuosity
Bifid Uvula/Cleft Palate
Wide-set eyes(hypertelorism)
Pectus deformity
Translucent skin
Hypermobility
Chiari Malformation
History of EDS
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1682:Van Meekeran
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1888: Kopp*
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Dutch Surgeon
Case of a father & his son
1892: Chernogubov**
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Russian Dermatologist with first
modern case description
George Albert, Spaniard w/ EDS
1682 lithograph
*Kopp, W. Demonstration zweier Faelle von 'cutis laxa'. Muench. Med. Wschr. 35: 259 only, 1888
** Royal Academy of Sciences in Russia
History of EDS
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1901: Evard Ehlers (1863-1937)
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Danish Dermatologist (Copenhagen)
described a variant of Cutis Laxa.
1908: Henri Danlos (1844-1911)
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French Dermatologist who described a
young boy w/ skin laxity & chronic contusions
at a Paris convention
First known picture of
EDS Patient- 1908 Paris
Dr. Henri-Alexandre Danlos
What does IWF World Weightlifting Championships and
EDS have in Common?
2 blocks apart
IWF World Masters Weightlifting
Championships Medical Team
9/2014
Amager Hospital (former
Fredickerson Hospital) where
Evard Ehlers first saw patient
with EDS in 1901!
Recent History of EDS
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1949: Ehlers-Danlos
given formal name
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1955: Defect is in
collagen: Jansen
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1968: Heterogenic
transmission:Beighton
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1985: Ehlers-Danlos
National Foundation
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1998:New Nosology
(classifications)
Father of Modern Medical Genetics

In 1966, McKusick
published the first edition
of Mendelian Inheritance
in Man, a compendium of
inherited disorders that
had 1,500 entries in that
printing. The book went
through 12 editions, the
last published in 1998,
before going online. It has
20,000 entries and is
continually updated
Dr. Victor A. McKusick, a Johns Hopkins
professor widely considered the father of
medical genetics, was awarded the prestigious
Japan Prize in Medical Genetics and Genomics
in 2008, before his death at 97yo in 2011.
People with EDS
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Nicolas Pagninni, virtuoso
violinist, 1700s,
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“the devil incarnate”
Famous Rubber Men of India,
1800s
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traveling circuses
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Actually from Romania
Pia Zadora
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1980s actress
What is the Incidence of EDS?
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In 1970, Beighton - 1 in 20,000 live birth*
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In 1985, Byers - 1 in 5,000 live births**
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In 1990, Aulicino -1 in 2,500 live births
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*Beighton, P. et al; 1970
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**Byers, PH, Holbrook KA., Ann NY Acad Sci: 1985;460:pp. 298
Reason for Changing Incidence
Under diagnosis of milder cases
Healthcare providers more familiar w/ EDS.
Symptoms often mimic other conditions.
Ease of accessing medical information
What is Ehlers-Danlos Syndrome?
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“Group of heritable disorders affecting
the collagen, often characterized by:
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Hyper-extensible skin
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Hyper-mobile joints
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Easy bruising
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Fragility of the skin
Classic signs of Classical Type
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Thin, hyper-elastic skin
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Angle of Jaw
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Elbow, mid-forearm, mid-thigh
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“Pinchable” skin in palm
Violaceous, “Cigarette Paper” Scar
tissue over
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Forehead / Chin
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Extensor surfaces (elbows, knees, shins)
Small joint laxity
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Fingers, Hands, toes
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Increase sub-talar motion/ ankle laxity
Evard Ehler’s Patient, circa
1903
Laboratory Diagnosis
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As of 2015, still a clinical or PHENOTYPIC
diagnosis
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If involved in research OR if there is a
question of which type of EDS or if
another condition is present
(Dermatospraxis, Cutis Laxal, etc)
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Blood or Skin Biopsy for GENETIC
TESTING (molecular genetics)
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COL 5A1 and COL5A2 genes
Skin Biopsy for ELECTRON MICROSCOPY
(used mostly in Heifelberg, Germany)
Mao et al. J Clin Invest. 2001;107(9):1063-1069. doi:10.1172/JCI12881.
Youth Concerns
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Protection from trauma
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Normalize childhood experience
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Avoid parental “hovering”
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Appropriate laceration repair
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Family doctor/ Pediatrician
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Plastic Surgeon
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“trained” parents
Promote non-contact sports, when
possible.
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Protect if child wants to play
Wound Closure Techniques in Classical
type
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Sutures or Stitches
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Simple interrupt
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Horizontal mattress (to secure large
wounds)
Dermabond (a.k.a. Super glue)
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Face
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Scalp: long hair? Tie and bead of glue
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Avoid in cuts over joints
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Steri-Strips
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Surgical staple gun
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Butterfly band-aids
Typical “Fish
mouth” laceration
over knee
Adolescent / Young Adult Concerns:
GIRLS
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“fitting in” with social groups
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Avoid “stupid human or circus tricks”
GIRLS:
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Yoga pants: GOOD
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When MENSES start: needs to improve CV
exercise (Counters POTS)
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Start strength training between 10-13 y.o.
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SCAR
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Mederma topical
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Vitamin E cream
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Avoid tanning beds, long exposure to UV
radiation
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Hats, long arm/leg pants
Adolescent / Young Adult Concerns:
BOYS
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“fitting in” with social groups
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Avoid “stupid human or circus tricks”
BOYS:
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Start strength training between 10-13 y.o.
(especially if swimmer, gymnastics, wrestler,
etc)
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Avoid contact sports
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Protect SHINS/KNEES/ELBOWS
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SCAR
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Mederma topical
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Vitamin E cream
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Avoid tanning beds, long exposure to UV
radiation
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Hats, long arm/leg pants
Mature Adult Concerns
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Progeria-prevention
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Sun/UV protection
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Avoid obesity
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Stay VERY active
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10,000 steps a day
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Swim/bike/walk
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Avoid excessive running
Arthritis
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Small Joints
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Large Joints
PAIN CONTROL
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Discuss with your PCP
Develop a plan that uses a TIERED
SYSTEM
NO PAIN – NO PILLS
Minimal pain (1st Tier): Tylenol,
Moderate pain (2nd Tier): NSAIDs,
topicals, patches.
Severe Pain (3rd Tier): Tramadol, avoid
daily narcotics (only during flare up
2x/week)
Accupuncture
Biofeedback
Massage
Chiropractic no more than 2x/month
OVERVIEW

Protect the skin
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When laceration occurs, be prepared
and have a plan
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Stay active
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Allow kids to be kids
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protect their skin and joints
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Redirect, rather than say “No”
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Avoid Obesity
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Tiered Pain control