Medscape article on EDS

January 20, 2004

PEDIATRICS

A 6-Year Old Contortionist

Tim has extreme flexibility of all his joints. What could the diagnosis be?

J Pediatr Health Care 17(6) 2003

If you can't view the article, let me know and I'll email it to you.

Love Lana

" 'Be who you are and say what you feel because those

who mind don't matter and those who matter don't mind.' "

Dr. Suess

January 20, 2004

Could you please send me the article?

C.

January 20, 2004

Could you please send me the article?

C.

January 20, 2004

Could you please send me the article?

C.

January 21, 2004

, I'll send it from home tonight, OK? I don't have access to my file

cabinet here at work.

Love Lana

January 21, 2004

Hi Lana,

That is perfect. Thank you very much :-)

Love,

Fay.

> Fay, I'll send it tonight - I'm at work and can't access my file

> cabinet here - OK?

>

> Love Lana

>

January 21, 2004

Hi Lana,

That is perfect. Thank you very much :-)

Love,

Fay.

> Fay, I'll send it tonight - I'm at work and can't access my file

> cabinet here - OK?

>

> Love Lana

>

January 21, 2004

Here you go, Fay!

From Journal of Pediatric Health Care

A 6-Year Old Contortionist

Posted 01/09/2004

Sally Walsh, MSN, RN, CPNP

Case Study

Tim has arrived with great fanfare for his first grade physical. This family

is particularly well-known to you since his mother is a pediatric nurse at the

local children's medical center and is studying to become a pediatric nurse

practitioner.

During the course of the interval history, Tim's mother tells you she has had

to suspend her studies since she has been quite ill for the past several

months. She presented with extreme fatigue and was diagnosed with

cardiomyopathy.

She also had a positive anti-nuclear antibody, so her initial diagnosis was

systemic lupus erythematosis. Recently, the rheumatologist who has been

following her in consultation with a cardiologist suggested another diagnosis.

He

reviewed her medical history, which included psoriasis, hypothyroidism, frequent

bruising, excessive bleeding postpartum, and hyper-flexibility of all joints,

and told her he was considering a syndrome that includes this constellation of

symptoms. She is now concerned that Tim has the same syndrome since he has

some of the same traits.

On physical examination you note these findings: htâ€”48 1/2 inches, wtâ€”41 1/2

pounds, BP88/46. All physical findings are normal except for a small scar

below his left eyebrow and extreme flexibility of all his joints. Indeed, he is

delighted to show you all the contortions he can do on the exam table!

A review of Tim's medical history shows several items of interest: (a)

duskiness with feedings as a young infant which was diagnosed as

gastroesophageal

reflux and managed with medications and positioning, ( two episodes of

cyanotic lips and hands after naps at age 18 months which was diagnosed as

vasospasm

by a pediatric cardiologist (an EKG done at that time was normal), © a

fractured clavicle at age 3 years, and (d) a laceration over his right eye at

age 2

1/2-yrs that was slow to heal. Tim's echocardiogram, done on the

recommendation of his mother's cardiologist, was normal. Other than the recent

development

of migraine headaches, he has been in good health and without injury for the

last two years.

Case Studies Quiz

What syndrome do you think is being considered for Tim's mother?

What are some of the more serious forms of this syndrome?

What guidance would you give to this mother about Tim?

Questions and Answers

1. What syndrome do you think is being considered for Tim's mother?

A syndrome that involves fragility of blood vessels and hyperflexibility of

the joints must focus on disorders involving connective tissue. The specific

syndrome that fits Tim's mother's medical history is Ehlers-Danlos Syndrome.

This is a group of genetically heterogeneous connective tissue disorders. The

integrity of the tissues is easily disturbed, as evidenced by the fragility of

skin and blood vessels. Wound healing is delayed, with relatively inadequate

scar tissue, and prolonged hemorrhage may follow trauma (, 1997). Affected

children appear normal at birth, but skin hyperelasticity, fragility of the

skin and blood vessels, and joint hypermobility develop. The essential defect is

a quantitative deficiency of collagen (Darmstadt, 2000).

2. What are some of the more serious forms of this syndrome?

The genetic blueprint of this syndrome is autosomal dominant with wide

variations in expression. Ten distinct forms of Ehlers-Danlos syndrome have now

been

delineated. All types include the effects of collagen deficiency, but with

varying degrees of severity and system involvement. Several types are very mild

in their presentation with minor skin manifestations and joint involvement

limited to hands and feet or just hyperflexibility of all joints.

Several others manifest in more serious complications. The gravis type is

characterized by premature birth caused by rupture of membranes, skin

hyperelasticity and fragility, easy bruising, generalized and severe joint

hypermobility,

scoliosis, and mitral valve prolapse. Insignificant lacerations may form

gaping wounds that leave broad, atrophic, papyraceous scars. Additional

cutaneous

manifestations include molluscoid pseudotumors over pressure points from

accumulations of connective tissue. Life expectancy is not reduced.

The ecchymotic type shows the most dermal thinning of all; consequently the

venous network is prominent. The skin has minimal hyperextensibility, and the

joints are not hypermobile, except perhaps during childhood. Premature birth;

extensive ecchymoses from trauma; a high incidence of keloids; rupture of the

bowel, especially the colon; uterine rupture during pregnancy; rupture of the

great vessels; dissecting aortic aneurysm; and stroke all contribute to

increased morbidity and shortened life span. Patients should be advised to avoid

becoming pregnant, avoid activities such as trumpet playing that raise

intracranial pressure as a result of the Valsalva maneuver, and minimize trauma

to the

skin (Darmstadt, 2000).

A third type, arthrochalasis multiplex congenital, is characterized by short

stature, marked joint hyperextensibility and dislocation, and moderate

hyperelasticity and bruisability of the skin. A sub-type of this disorder, known

as

dermatosparaxis, includes: premature rupture of the membranes; delayed closure

of the fontanels; skin fragility and laxity; easy bruising; growth

retardation; short limbs; umbilical hernia; and characteristic facies with

micrognathia,

jowls, and prominent, puffy eyelids (Darmstadt, 2000).

3. What guidance would you give this mother about Tim?

Tim most likely has the mildest form of this disease. His examination shows

the hyperflexibility of his joints and the scarring that can accompany this

disorder, although he has not had further injuries that resulted in either

excessive bruising or scarring. A genetic consult is needed to confirm Tim's

diagnosis and determine the severity of his disease. An appointment was

scheduled for

Tim and his mother to be seen, but, since school and athletic programs were

starting before his appointment, a telephone consult was placed to the genetics

department for guidance on any sport restrictions. The genetic counselor

reported that, because Tim's disease was one of the connective tissue disorders

and his presentation was probably a mild version of Ehlers-Danlos syndrome, his

diagnosis would most likely be a " clinical " one. In more complex cases, skin

biopsies and other diagnostic criteria would be used to establish the diagnosis

and severity of the disease. She felt Tim would not need any limitations of

physical activity before he was seen by the genetics department. As part of

that evaluation, he will also be examined by ophthalmology, cardiology, and

orthopedic physicians.

Since Tim has recently started to have migraine headaches, it was decided to

include a neurological examination to insure that the reasons for his

headaches are not part of this syndrome. Although Tim's presentation seems mild,

if

athletics are to be a part of Tim's activities before his genetic evaluation,

caution should be exercised to avoid any joint dislocation or skin trauma. Since

Tim also has the accompanying symptom of migraine headaches, sports such as

weight lifting, wrestling, and football that may increase intracranial pressure

as a result of the Valsalva maneuver should not be chosen until cleared by

neurology. Tim's mother, maternal uncle, and maternal grandfather are all now

scheduled for a genetic consultation. Tim's mother has now recovered from her

cardiomyopathy and is returning to her studies.

Reprint Address

Reprint requests: Sally Walsh, MSN, RN, CPNP, 11 Appletree Lane, Lexington,

MA 02420; Email: walsh@...

References for:

A 6-Year Old Contortionist

Darmstadt, G. (2000) in Textbook of Pediatrics, 16th Ed. Disorders of

the Dermis, W.B. Saunders, Philadelphia. 1921, 2013-2014.

K. 's Recognizable Patterns of Human Malformation. In Connective

Tissue Disorders, W.B. Saunders, Philadelphia 1997, 482-483.

University of Washington, Dept. of Orthopaedics & Sports Medicine,

Ehlers-Danlos Syndrome: Management and Treatment. Retrieved August 24, 2003,

from

http://www.nlm.nih.gov/medlineplus/ehlersdanlossyndrome.html.

===================================================================

From Pediatric Nursing

Ehlers-Danlos Syndrome, Classical Type: Case Management

Posted 01/13/2004

Sara E. Whitelaw

Abstract and Introduction

Abstract

As the field of genetics expands, there will be more need for health care

professionals to possess basic knowledge of genetic conditions and patterns of

inheritance to assist their patients and to make the proper referrals.

Ehlers-Danlos Syndrome (EDS) is a group of genetic connective tissue disorders

that

affects approximately 1 in 5,000 live births, including males and females of all

racial and ethnic groups. The main characteristics of EDS are skin

hyperextensibility, tissue fragility, and joint hypermobility. Diagnosis of EDS

is often

difficult due to the complexity of symptoms and lack of specific genetic

tests. However, once a diagnosis is suspected or confirmed, nurses play a vital

role in assisting the patient and family to manage the disorder. This article

describes EDS symptoms and genetic basis, provides suggestions for management,

and reviews resources available for health care providers, families, and

patients with EDS.

Introduction

Ehlers-Danlos Syndrome (EDS) is a heterogeneous group of heritable connective

tissue disorders. The syndrome can be described as heterogeneous because

there are six major subcategories of EDS, each with slightly different

characteristics and causes. The main characteristics of EDS are skin

hyperextensibility,

tissue fragility, and joint hypermobility. In addition to these three major

characteristics, EDS can manifest easy bruising, prolonged bleeding, mitral

valve prolapse, and chronic joint pain (Beighton, De Paepe, Steinmann,

Tsipouras,

& Wenstrup, 1998). The six major types of EDS are (a) classical type, (

hypermobility type, © vascular type, (d) kyphoscoliosis type, (e)

arthrochalasia

type, and (f) dermatosparaxis type (Beighton et al., 1998).

Genetic Basis

EDS is caused by abnormalities or defects in the collagen fiber structure

(Ehlers-Danlos National Foundation [EDNF], 2002). Collagen is a fibrous protein

that gives strength to connective tissue. When collagen is abnormal or damaged,

the connective tissue is weakened, and this causes instability of skin,

joints, and tissues. The specific collagen defects for the Classical type EDS

have

been found on the collagen V alpha-1 and alpha-2 gene (COL5A1 and COL5A2). The

COL5A1 gene is located on the long arm of chromosome 2q31. The COL5A2 gene is

located on the long arm of chromosome 9q34.2-34.3 (Online Mendelian

Inheritance in Man [OMIM], 2002).

EDS can be described as heritable or inheritable because it is passed on

within families from one generation to the next, through the family genes. Genes

exist in pairs; a child receives one half of each gene pair from each parent,

and the resulting new gene pairs determine the child's traits (Lashley, 1998).

It is important to note that there is no control over which genes get passed

on from parent to child.

Every person has 23 pairs of chromosomes (unless there are mutations causing

pairs to be disrupted). Twenty-two of the pairs are called autosomes, and the

23rd pair contains the sex chromosomes, which determine male or female sex.

The specific mode of inheritance for Classical type EDS is autosomal dominant

inheritance. This means that the mutant gene is located on an autosome rather

than a sex chromosome, and males and females are equally affected when the

mutant gene is present (Lashley, 1998). The fact that the EDS gene is dominant

means that a single gene with a mutation is necessary for the effects of EDS to

be

expressed, as opposed to recessive inheritance where two copies of the gene

with a mutation are necessary for the trait to be expressed. If one parent is

affected with EDS and one parent is normal, they have a 50% risk of having an

affected child and a 50% chance of having a normal child (Lashley, 1998). Each

type of EDS is unique to a family or is said to " run " in a family (EDNF,

2002). In other words, a parent with Classical type EDS will not have a child

with

a different type.

Epidemiology

The prevalence of EDS is 1 in 5,000 live births (Berglund, Nordsrom, &

Lutzen, 2000; Blereau, 1996; Hagen, 1993; & Cooley, 2000). Although the

majority of sources agree with this rate of prevalence, there are some that cite

other rates such as 1 in 5,000 to 10,000 or fewer than 1 in 20,000 (EDNF, 2002;

University of Washington Department of Orthopedics and Sports [uWDOS], 2002).

EDS affects both males and females of all racial and ethnic groups.

Identification of Potential Cases

History

Certain findings in a review of a patient's history can lead to suspicion for

EDS. Reports of skin that is easily bruised, torn, or scarred are common. In

addition, a patient may have had frequent dislocations of the shoulders and

knees. The easy bruising, scarring, and dislocations may bring attention to the

patient due to suspicion for child abuse ( & Cooley, 2000). Joints that

hyperextend often cause chronic pain. Medical professionals frequently

disregard this chronic pain when no cause can be determined. Family members with

similar characteristics can contribute to a positive family history; therefore,

it

is important to ask about the health history of family members. Delayed motor

development may also be in the patient's history due to hypotonia caused by

EDS. The most common findings in a history review of a patient with EDS are

easily bruised skin, scarring, and dislocations.

Assessment

The classic findings for each type of EDS are the three major criteria of

skin hyperextensibility, tissue fragility, and joint hypermobility. A major

criterion has high diagnostic specificity, which means that people without the

criterion truly do not have EDS (, 1997). These major criteria have

diagnostic specificity because skin hyperextensibility, tissue fragility, and

joint

hypermobility are not commonly found in other diseases and are also not common

in the general public. One or more of these three major criteria are required

for diagnosis (Beighton et al., 1998).

The presence of one or more minor criteria is necessary to distinguish a

specific type of EDS. Nine minor criteria are specific to the Classical type

EDS:

(a) smooth velvety skin, ( molluscoid pseudotumors, © subcutaneous

spheroids, (d) complications of joint hypermobility, (e) easy bruising, (f)

muscle

hypotonia, (g) signs of tissue extensitibility and fragility, (h) surgical

complications, and (i) positive family history (Beighton et al., 1998). Minor

criteria are less diagnostically specific because they are found in other

conditions. Minor criteria cannot be used to diagnose EDS, but are useful for

differentiating a diagnosis for a certain type of EDS when one or more major

criteria

are present.

Joint hypermobility can be assessed using the Beighton scale (as cited in

Beighton et al., 1998). The scale tests five performances of joint mobility and

has a maximum score of nine points. A score of at least five out of nine

determines joint hypermobility. The first performance is passive dorsiflexion of

the

little fingers beyond 90 degrees. One point is given for each hand that

demonstrates this feature. The next performance is passive apposition of the

thumbs

to the flexor aspect of the forearm. One point is given for each hand. The

third performance is hyperextension of the elbows beyond 10 degrees, one point

for each elbow. The fourth is hyperextension of the knees beyond 10 degrees,

one point for each knee. Finally, the fifth test is the forward flexion of the

trunk with knees fully extended. If the palms of the hand can rest flat on the

floor, one point is given.

Genetic Referral and Testing

Families should be referred for genetic counseling if one or more major

criteria are present in one or more family members because diagnosis is mainly

based on clinical features. At present, there is no highly sensitive genetic

testing available for the Classical type EDS. A high level of sensitivity is

important in genetic testing. Sensitivity describes the ability of the test to

identify people who truly have the condition.

Although a specific genetic test to diagnose EDS is not available, other

types of tests are able to identify EDS in some families. Skin biopsies examined

by electron microscope have revealed abnormal collagen fibril structure

(Beighton et al., 1998; Dame, Hausser, Geukens, & Brenner, 2001; De Paepe et

al.,

1987; UWDOS, 2002). Abnormal electrophoretic mobility of the proa1(V) and

proa2(V) chains of collagen type V has also been detected in some families

(Beighton

et al., 1998; Dame et al., 2001; EDNF, 2002). Electrophoresis is a method of

analyzing protein particles. These particles move with different velocities

depending on the charges carried by the protein (, 1997). Abnormal

electrophoretic mobility of the collagen describes the difference in the way

these

collagen proteins move in relation to normal collagen proteins when examined by

electrophoresis.

Post-Diagnosis Care

Management of EDS consists mostly of palliative and preventative care.

Regular evaluation of nutrition, growth, eyes, heart, skin, and joints by a

medical

professional familiar with EDS is important for maintenance. Treatment of

symptoms as they arise and appropriate education is valuable for patients and

their families.

The loose joints caused by EDS can be painful. The pain may be alleviated

with non-steroidal anti-inflammatory medications. However, bracing or fusion of

joints may be necessary to provide more joint stability and to reduce pain

(Hagen, 1993; UWDOS, 2002). Physical therapy and occupational therapy are

important additional treatments for most patients. Physical therapy can teach

patients

how to strengthen muscles without stressing joints and how to protect their

joints. Occupational therapy is useful when assistive devices are necessary for

support or protection of joints and ligaments at risk for injury.

Avoiding injury is essential and includes making homes safe to prevent falls

and avoiding high-impact or collision sports. Weight lifting, stretching, and

any activities that cause the joints to lock are contraindicated due to the

stress on the joints. Children may enjoy demonstrating the hypermobility of

their joints to their peers, but this should be avoided because the practice can

lead to early degenerative joint disease.

Skin care is significant to prevention of complications for a patient with

EDS because the skin is easily damaged. Using mild soaps and avoiding adhesive

bandages will protect the fragile skin. People with EDS should avoid excessive

sun exposure. Using sunscreen everyday as well as wearing long sleeves, long

pants, and a hat can help protect against sun damage to skin.

Resources

Although no specific tests or treatments for EDS exist, there are numerous

resources available for families or individuals with EDS and for health care

providers (see Table 1). Beighton et al. (1998) wrote a classic article about

EDS

that describes a revised classification of the different types of EDS and

outlines major and minor diagnostic criteria for each type. This article serves

as a most valuable tool for health care providers and may be applicable to

families or individuals with EDS depending on their level of education and

understanding of the condition.

The EDNF has an excellent Web site for patients, families, the public, and

health care providers. The EDNF can be contacted through mail, a toll free phone

number, fax, or email. The Web site offers links to news, information and

articles, a kids page, support groups, and links to other Web sites related to

EDS. The EDNF uses the new classification of types established by Beighton et

al. in 1998. The EDNF also publishes a newsletter called Loose Connections but

requires a membership fee for the subscription.

The OMIM is a Web resource that is useful for health care providers. The OMIM

describes the genetic basis for conditions and provides links to visual maps

of the genes involved in specific conditions. The EDNF Web site provides a

link to the OMIM site, so it is possible that families or individuals with EDS

could benefit from some aspects of this site. The OMIM site may cause confusion,

however, because the old classifications of EDS are used.

EDS Today is a " newsletter for, by, and about people with EDS " (EDS Today,

2002, p. 1). The newsletter includes information about research, life

experiences of people with EDS, and ideas on treatment from people with EDS. EDS

Today

can be reached by mail, phone, fax, or email. There is a small subscription fee

for the newsletter. EDS Today may provide some good information for families

and individuals with EDS, but there is no review of the content. Health care

providers may find this site interesting and informative regarding what their

patients are learning, but another source would be more reliable for health

care provider use.

The UWDOS has an online article about EDS. The article provides an

informative but easy-to-understand description of EDS, its incidence, genetic

factors,

symptoms, diagnosis, management, treatment, and ways to cope. Although the site

states the incidence as fewer than 1 in 20,000 and most sites state incidence

as 1 in 5,000, this site is a good resource for individuals and families with

EDS. The UWDOS can be contacted by phone as well as through the Web site.

These resources can be valuable tools for individuals and family members who

may be newly diagnosed and overwhelmed with what an EDS diagnosis means. Those

with an established diagnosis may benefit from contributing their experiences

and learning from the experiences of others. Health care professionals will

find these resources to be a foundation for learning about EDS, its treatment,

and how it affects individuals and families. All resources should be evaluated

to determine the benefit and application potential for specific cases.

Nursing Implications

The field of genetics is expanding and the amount of genetic information

available is increasing. Due to this growth, there is a need for nurses to

possess

knowledge of genetic disorders as well as genetic patterns of inheritance.

Knowledge of EDS and other genetic conditions is necessary so patients feel

understood and can receive the support they need for their chronic conditions

(Berglund et al., 2000).

The nursing role is valuable for many aspects of the care of the patient and

family with EDS. Once the diagnosis of EDS is suspected or made official, the

nurse with knowledge about EDS can play a significant role, specifically

through referral to or providing genetic counseling for the family.

Post-diagnosis,

the nurse may participate in the management of EDS through education of the

patient and family, creation of a plan of care, and collaboration with other

health care providers.

Children with EDS need nurses to be their advocates. These children may need

special protection from injury, but they still need to be active, play, and

have opportunities to make friends. The nurse can educate teachers, parents, and

other caretakers of the child regarding activities that are safe and the need

for the child with EDS to participate with peers. Safe activities children

may participate in include non-contact sports such as swimming or golf, reading,

hobbies, and playing musical instruments. Physical education classes in

school may be allowed with certain modifications. A child with EDS need only

avoid

rough play and activities that may risk injury or overextend joints. Every

effort should be made to modify activities so that the child with EDS can join

their peers and not feel isolated or different.

Researchers are currently studying the mutation pattern of the genes involved

in EDS (Beighton et al., 1998). Diagnosis of EDS can be difficult due to the

wide range of manifestations and lack of specific genetic tests. Nurses may

participate in research for EDS and should expose themselves to new literature

regarding EDS. Research may one day lead to a genetic test for diagnosis of EDS

and a more effective treatment regimen for people with EDS.

CE Information

The print version of this article was originally certified for nurse CE

credit. For accreditation details, contact the publisher. Pediatric Nursing,

J. Jannetti, Inc, East Holly Avenue Box 56, Pitman, New Jersey

08071-0056,

phone

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Ehlers-Danlos Syndrome, Classical Type: Case Management

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from www.ednf.org

Hagen, K. (1993). What's wrong with this patient? RN, 56, 34-37.

Lashley, F.R. (1998). Gene action and patterns of inheritance. In Clinical

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January 21, 2004