EDNF Center for Clinical Care &

Research at GBMC

2014 PHYSICIANS

CONFERENCE

September 15, 2014

Ehlers-Danlos Syndromes

in the Pediatric Population

Antonie D. Kline, M.D.

Director of Pediatric Genetics

EDNF Center for Clinical Care and

Research at GBMC

Harvey Institute for Human Genetics

Greater Baltimore Medical Center

My Presentation

Overview of EDS

Case presentations

Clinical findings

Familial aspects

Management in the pediatric

population

Pediatric genetics practice

experience

EDS, General Facts

Hereditary disorders of connective tissue

Most due to defects in collagen but not all

Most types autosomal dominant

Most types have skin involvement/fragility

and joint laxity

Can have involvement of cardiovascular

system

Can be progressive and unpredictable

Likely more common than 1:5000

EDS, Major Types

Classical Type – Joint laxity, very

hyperextensible fragile skin, thin atrophic

scars with poor wound healing

Hypermobility Type – Most common, marked

joint laxity, soft doughy skin, normal scars

Vascular Type – Mild joint laxity, thin skin,

slow wound healing, normal scars

Other three major types rare

EDS, Major Types

Classical Type – Joint laxity, very

hyperextensible fragile skin, thin atrophic

scars with poor wound healing, chronic pain

Hypermobility Type – Most common, marked

joint laxity, soft doughy skin, normal scars,

chronic pain

Vascular Type – Mild joint laxity, thin skin,

slow wound healing, normal scars

Other three major types rare

EDS, Major Types

Classical Type – Joint laxity, very

hyperextensible fragile skin, thin atrophic

scars with poor wound healing, chronic pain,

aortic dilitation

Hypermobility Type – Most common, marked

joint laxity, soft doughy skin, normal scars,

chronic pain, aortic dilitation

Vascular Type – Mild joint laxity, thin skin,

slow wound healing, normal scars, risk for

aortic dilitation and arterial rupture

Other three major types rare

Autosomal Dominant Inheritance

http://www.tupbebek-

genetik.com/en/genetics/molecular-genetics

E

D

S

E

D

S

E

D

S

Case 1: 11 yo W M

• Medical History: Double jointedness, able to

do tricks, loose shoulder joints with recent

shoulder dislocation, does wrestling, rock

climbing

• Development: High IQ, dyslexia, executive

function issues, ADHD

• Family History: Mother with soft skin, tear in

anterior cruciate ligament, MGM with torn

rotater cuff; father was gymnast, few details

known

Beighton Score

• Assign on PE by examining major joints

• Hypermobility is Beighton score greater than 4/9

• Joint hypermobility? 1 point per item

Passive dorsiflexion 5th finger beyond 90 degrees? Right ________ Left ________ Points ___

Passive apposition of thumbs to flexor forearm? Right ________ Left ________ Points ___

Hyperextension of elbows beyond 10 degrees? Right ________ Left ________ Points ___

Hyperextension of knees beyond 10 degrees? Right ________ Left ________ Points ___

Forward flexion of trunk with knees extended so palms rest flat on floor? Point ____

Total points _____

http://hypermobility.org

/help-advice/ hyper

mobility-syndromes/

beighton-score

Case 1, cont.

• Physical Findings:

Normal growth, Beighton

8/9, mild scoliosis mid-

thoracic region, scapular

winging, skin

hyperextensibility, single

atrophic scar

• Diagnostic Study:

COL3A1 mutation testing

negative

• Likely classical EDS

Case 1, Follow-up

Seen at 12 and 14 years

Developed significant pain in multiple

joints and reflex sympathetic dystrophy

after injury to one joint

Developed abdominal pain, possible cyclic

vomiting, severe nausea/vomiting

Developed chronic headaches, possible

migraine with stress component – has

undergone acupuncture with some relief

Undergoing work-up for POTS

Case 1, Management

Echocardiogram: Normal, will repeat in 5

years to assess aortic root size

Activities: Curtail wrestling, rock climbing;

highly recommend swimming and other

lower impact sports/exercises

Joints: Recommend physical therapy,

including warm water; myofascial trigger

point massage; support for painful joints

but not total immobilization

School: Letter written for them to make

accommodations

Cardiac and Aortic Involvement in

EDS Risk for dilation of aortic root

Risk for valvular involvement, especially MVP

Recent study Atzinger C, et al. J Pediatr 158:826-30,2011.Epub 2010 Dec 28

showed increased size of aortic root in 3% but

with rare dilation at 15 years of age or more

Also showed that incidence of MVP was 6%

although sometimes not benign

Recommend echocardiogram in all children

with EDS; repeat in 5 years if normal through

age 15 years and refer if abnormal

EDS and Pain Management in

Pediatric Population Not well studied and needs to be

Overall recommendations

Physical therapy, especially warm water

Regular strengthening of muscles, minimize

contact sports and encourage swimming

Use Epsom salts in bath or foot soaks

Myofascial trigger point release

Referral to PM&R physicians or Pain Clinic

Medications: Analgesics, no narcotics, consider

topical approach (eg Lidocaine, Indomethicin,

Diclofenac); no compound creams below 15 years

Use accommodations in school, handicapped

parking for malls, be sensible

Case 2: 7 mo W F

Medical History: Uncomplicated

prenatal/ neonatal history, at 6 months

noted to have very mobile joints, knee

dislocations, episodes of screaming

Family History: Maternal family history of

multiple joint dislocations, flexible joints, soft

stretchy skin

Physical Findings: Normal growth, light blue

sclerae, very flexible joints with clicks upon

movement, no Beighton, smooth soft skin

Likely hypermobile EDS

Case 2, Follow-up Seen at 14 months for follow-up, stable

Echocardogram normal

Not seen again until 10 years

Developed arthralgias, leg weakness and

severe back pain, hip pain, miserable with

pain

Diagnosed with hip synovitis, bilateral

trochanteric bursitis

Given steroid injections, Lidoderm patch,

weekly Methotrexate, also given Elavil, Zoloft,

Rocicet (Oxycodone/Tylenol) and Tylenol

Case 2, follow-up cont.

Using wheelchair for 2 months prior to our

visit

Developed confusional migraines

Developed abdominal pains, constipation,

taking Prilosec and Prevacid

Developed nocturnal enuresis

Normal development, doing well in school

but absent frequently

Case 2, 10 yo

Physical Findings:

normal growth,

Beighton score 4/9,

joints with clicks, mild

scoliosis mid-thoracic

region, flat feet,

smooth soft skin with

atrophic scar on side

of abdomen

12 yo in follow-

up, doing better

Case 2, cont.

Upright MRI brain, spine and CT scan upper

cervical spine showed no Chiari malformation

but 50% foraminal narrowing at C3-4 and

straightening of mid-lower cervical lordosis

Now taking Tylenol, Tramidol, Cymbalta,

Neurontin and Diazepam for pain, and getting

trigger point injections; pain has improved and

she is no longer using wheelchair regularly

Developed episodic dizziness with positional

change and headaches; diagnosed with POTS

and increased fluid intake, taking salt tablets

Doing well in school but missed a lot

Postural Orthostatic Tachycardia

Syndrome in EDS

Orthostatic symptoms: dizziness,

lightheadedness, weakness, change in

vision, palpitations

Older adolescents: increase in HR by 30-40

bpm within 10 min of standing up or tilting up

without change in bp

Children less than 13 years: HR above 130,

or increase in HR by 40 bpm similarly upon

rising Benarroch EE, Mayo Clin Proc 87:1214-25,2012.Epub 2012 Nov 1

Treatment: hydration, electrolytes, rising up

slowly, compression stockings, exercises

Case 2, Management

Echocardiogram: Normal, repeat in 5

years

Joints: Continue pain clinic and current

pain management; use Epsom salts in

bath or foot soaks; encourage swimming,

resume PT if indicated

C-spine: Referral to pediatric

neurosurgery

POTS: Increase fluids and salt intake

School: Continue to use accommodations

Case 3: 9 yo W M

Medical History:

Always had loose joints, easy bruising, fragile

blood vessels, headaches

At 9 years diagnosed with Chiari

malformation s/p neurosurgical repair, still

with headaches, fatigue

Also with GERD; ADHD, anxiety, delayed

development, autism spectrum disorder

Family History: Sisters with hypermobile EDS,

one with Chiari malformation and possible

tethered cord, mother with EDS

Case 3, cont.

Physical Findings: normal

growth, Beighton 5/9, feet

flat with inwardly rotated

ankles, soft skin

Diagnostic Studies: SNP

microarray normal

Recommendations:

Follow symptoms, consider

repeat brain/neck studies

Echocardiogram: normal,

repeat in 5 years

Chiari and EDS

Craniocervical junction abnormality can occur

along with A. Chiari type I malformation, both of

which is known to accompany EDS Milhorat TH, et al., J

Neurosurg Spine 7:601-9,2007

Full evaluation for this: upright brain MRI,

upright cervical spine MRI in flexion and

extension, and CT scan of the upper spine in

neutral, rotation to the right, rotation to the left

(specific centers specialize in upright MRI)

If present, cervical traction and/or surgical

decompression can provide neurologic

improvement Menezes AH, J Neurosurg 116:301-9,2012.Epub 2011 Nov 18

EDS and Pediatric Genetics Practice

A review of 101 patients seen

Female to male ratio is 58% to 42% or 1.38:1

Age range 7 months – 20 years

Race: White %, Black 10%, Asian 4%

Referrals

Made by

77% pediatrics

20% orthopedics, 3%psychiatry

Reasons for referral

64% hypermobility, rule out EDS

20% rule out Marfan syndrome

5% r/o OI, 5% hypotonia, 5% MCA

Joint Hypermobility

EDS and Pediatric Genetics

Practice, cont. Diagnosis:

25% Classical EDS

66% Hypermobile EDS

0% Vascular EDS

1% Arthrochalasia EDS

1% possible OI/EDS phenotype

7% unclear type of EDS

Familial Cases: 76% (74% maternal, 11%

paternal, 13% unknown), with 8% “likely

familial”

Can Do Tricks with Joints

EDS and Pediatric Genetics

Practice, cont. Skin complications

Soft skin 79%

Abnormal scarring 33%

Bruising 28%

Joint complications

Fractures 18%

Dislocations 33%

Pain 46%

Beighton score >5 in 41%

Needing to use wheelchair 3%

Skin Involvement

in EDS

edstoday.org

www.skinversal.com

Stretchy Ears,

Cheeks, Skin

EDS and Therapy Issues

Swimming and bicycling recommended

Feet

Physical therapy and support (eg AFO’s)

Minimize walking, park in handicapped

spots

Hands

Splints for acute issues

Pen/pencil accomondations from OT

Ring splints for extra support

Foot Involvement

in EDS

EDS and Pediatric Genetics

Practice, cont.

Functional GI involvement 21%

Migraines 15%

Cardiac

Dilated aortic root 3%

Mitral valve prolapse 3%

POTS 6%

Behavior

ADHD 15%

Anxiety 8%

Depression 3.5%

EDS and Neurodevelopment

No major studies to evaluate this; several case

reports

Neurologic

Hypotonia 6%

Fatigue 8%

Chiari/craniocervical junction abnormality 2%

Development

Delayed, ID 8%

Learning disability 10%

Autism 4%

Ongoing evaluation to assess mitochondrial

function; fatigue may be related to this

Acknowledgements

Clair Francomano, M.D.

Marcia Ferguson, M.S., C.G.C.

Amy Kimball, M.S., C.G.C.

Christy Haakonsen, Sc.M., C.G.C.

Pat Williams

Linda Wiley

Greater Baltimore Medical Center

Ehlers-Danlos National Foundation