Classical Ehlers-Danlos Syndrome

EDNF National Conference
August 15 th , 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
No conflicts of interests
No Financial disclosers to reveal
All patients have given permission for their images/stories to be used
in this talk.

OBJECTIVES
Molecular Genetics (as best we know it as of 2015)
History of Ehlers-Danlos
Define signs / symptoms of Classical Type
Stages of Classical EDS
Youth concerns
Adolescent concerns
Adult concerns
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)
Found in bone, cartilage,
tendons, ligaments etc.
>>18 different types now
identified
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)
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
1682:Van Meekeran
Dutch Surgeon
1888: Kopp*
Case of a father & his son
1892: Chernogubov**
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

Dr. Henri-Alexandre Danlos
History of EDS
1901: Evard Ehlers (1863-1937)
Danish Dermatologist (Copenhagen)
described a variant of Cutis Laxa.
1908: Henri Danlos (1844-1911)
French Dermatologist who described a
young boy w/ skin laxity & chronic contusions
at a Paris convention
First known picture of
EDS Patient- 1908 Paris

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
1949: Ehlers-Danlos
given formal name
1955: Defect is in
collagen: Jansen
1968: Heterogenic
transmission:Beighton
1985: Ehlers-Danlos
National Foundation
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
Nicolas Pagninni, virtuoso
violinist, 1700s,
“the devil incarnate”
Famous Rubber Men of India,
1800s
traveling circuses
Actually from Romania
Pia Zadora
1980s actress

What is the Incidence of EDS?
In 1970, Beighton - 1 in 20,000 live birth*
In 1985, Byers - 1 in 5,000 live births**
In 1990, Aulicino -1 in 2,500 live births
*Beighton, P. et al; 1970
**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?
“Group of heritable disorders affecting
the collagen, often characterized by:
Hyper-extensible skin
Hyper-mobile joints
Easy bruising
Fragility of the skin

Evard Ehler’s Patient, circa
1903
Classic signs of Classical Type
Thin, hyper-elastic skin
Angle of Jaw
Elbow, mid-forearm, mid-thigh
“Pinchable” skin in palm
Violaceous, “Cigarette Paper” Scar
tissue over
Forehead / Chin
Extensor surfaces (elbows, knees, shins)
Small joint laxity
Fingers, Hands, toes
Increase sub-talar motion/ ankle laxity

Laboratory Diagnosis
As of 2015, still a clinical or PHENOTYPIC
diagnosis
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)
Blood or Skin Biopsy for GENETIC
TESTING (molecular genetics)
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
Protection from trauma
Normalize childhood experience
Avoid parental “hovering”
Appropriate laceration repair
Family doctor/ Pediatrician
Plastic Surgeon
“trained” parents
Promote non-contact sports, when
possible.
Protect if child wants to play

Wound Closure Techniques in Classical
type
Sutures or Stitches
Simple interrupt
Horizontal mattress (to secure large
wounds)
Dermabond (a.k.a. Super glue)
Face
Scalp: long hair? Tie and bead of glue
Avoid in cuts over joints
Steri-Strips
Surgical staple gun
Butterfly band-aids
Typical “Fish
mouth” laceration
over knee

Adolescent / Young Adult Concerns:
GIRLS
“fitting in” with social groups
GIRLS:
Avoid “stupid human or circus tricks”
Yoga pants: GOOD
When MENSES start: needs to improve CV
exercise (Counters POTS)
Start strength training between 10-13 y.o.
SCAR
Mederma topical
Vitamin E cream
Avoid tanning beds, long exposure to UV
radiation
Hats, long arm/leg pants

Adolescent / Young Adult Concerns:
BOYS
“fitting in” with social groups
BOYS:
Avoid “stupid human or circus tricks”
Start strength training between 10-13 y.o.
(especially if swimmer, gymnastics, wrestler,
etc)
Avoid contact sports
Protect SHINS/KNEES/ELBOWS
SCAR
Mederma topical
Vitamin E cream
Avoid tanning beds, long exposure to UV
radiation
Hats, long arm/leg pants

Mature Adult Concerns
Progeria-prevention
Sun/UV protection
Avoid obesity
Stay VERY active
10,000 steps a day
Swim/bike/walk
Arthritis
Avoid excessive running
Small Joints
Large Joints

PAIN CONTROL
Discuss with your PCP
Develop a plan that uses a TIERED
SYSTEM
NO PAIN – NO PILLS
Minimal pain (1 st Tier): Tylenol,
Moderate pain (2 nd Tier): NSAIDs,
topicals, patches.
Severe Pain (3 rd Tier): Tramadol, avoid
daily narcotics (only during flare up
2x/week)
Accupuncture
Biofeedback
Massage
Chiropractic no more than 2x/month

OVERVIEW
Protect the skin
When laceration occurs, be prepared
and have a plan
Stay active
Allow kids to be kids
protect their skin and joints
Redirect, rather than say “No”
Avoid Obesity
Tiered Pain control