Update on classification of EDS - PowerPoint Presentation

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Update on classification of EDS

2017 ILC foundation meeting

Hanna

Faghfoury

, MDCM, FRCPC, FCCMG

November 4, 2017

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Disclosure

I have no financial or other conflicts of interest to disclose

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Outline

At the end of this talk you should be able to:

Describe the rationale for updating the classification of EDS syndromes

Outline the differences between old and new classification of EDS

Summarize areas for future EDS research

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Reference

American Journal of Medical Genetics Part C: Seminars in Medical GeneticsMarch 2017“The Ehlers-Danlos Syndromes: Reports from the International Consortium on the Ehlers-Danlos Syndromes”

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History EDS classification

In 1988

“Berlin nosology”

established when molecular diagnostics was not yet discovered

Update in 1998

“

Villefranche

criteria”

when biochemical and genetic aspects were increasingly known

9 subtypes of EDS

“Major” and “Minor” criteria

Need identified for an update as the knowledge of clinical and molecular subtypes of EDS had expanded over past 2 decades

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Villefranche criteria

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Brighton criteria JHS

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THE 2017 INTERNATIONALCLASSIFICATION

13 subtypesAll types have in common: Joint hypermobility, skin hyperextensibility and tissue fragility Aims to regroup EDS subtypes based on genes and pathway function with the exception of hypermobile EDSAims to provide a standardized framework for management and homogeneity for future genetic research

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Hypermobile EDS (hEDS)

Replaces EDS III, hypermobility type EDS, hypermobility syndrome

hEDS

remains a clinical diagnosis

Genetic heterogeneity likely at play (with contributions of age, sex, environmental factors)

Aim of new criteria is to reduce heterogeneity of the patient population and facilitate efforts to discover the genetic cause of the syndrome

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Attempt to determine genetic basis of hEDS

Largely unsuccessful despite multiple attempts by multiple international groups

Only a few case reports have pointed to a specific genetic factor in

hEDS

:

one case report of a COL3A1 variant (

Narcisi

et al, 1994)

a variant of LZTS1 gene in 4 Belgian families (

Syx

et al, 2015)

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Clinical diagnosis of

hEDS

needs simultaneous presence of criterion 1, 2 AND 3

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Criterion 1: Generalized joint hypermobility (GJH)

Criterion met with Beighton score:≥6 pre-pubertal children and adolescents≥5 pubertal adults up to 50 yo≥4 adults over 50 yo

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Criterion 1: Generalized joint hypermobility (GJH)

If patient has acquired joint limitations AND is 1 point below Beighton score cutoff, GJH diagnosed if patient answers “yes” to 2/5 questions on a 5 point questionnaire

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Criterion 2: Two or more of the following features (A, B or C)

Systemic manifestations of a more generalized connective tissue disorder (min 5/12)

: unusually soft/velvety skin, mild skin

hyperextensibility

, unexplained

striae

, bilateral

piezogenic

heel papules, recurrent or multiple

herniae

, atrophic scarring, organ prolapse, dental crowding and high/narrow palate,

arachnodactyly

, arm span to height

≥1.05, Mild mitral valve prolapse, and aortic root dilatation

Positive family history of 1+ first degree relatives independently meeting the current diagnostic criteria for

hEDS

Musculoskeletal complications (min 1/3)

: pain in two or more limbs recurring daily for at least 3 months, chronic widespread pain for

≥3 months, recurrent joint dislocations in the absence of trauma

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Criterion 3: All the following prerequisites must be met

Absence of unusual skin fragilityExclusion of other heritable and acquired connective tissue disorders including autoimmune disorders (RA, Lupus)Exclusion of alternative diagnoses that may cause joint hypermobility (eg. Osteogenesis imperfecta)

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But what about all the other features?

Many other features are described in hEDS but at the current time are not sufficiently specific/sensitive to be included in the formal diagnostic criteria: Sleep disturbancesFatiguePOTSFunctional GI disordersDyautonomiaAnxiety/Depression

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Clinical spectrum of joint hypermobility

AsymptomaticJH

SymptomaticJH

hEDS

HSDs

Other conditions/genetic syndromes

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Clinical spectrum of joint hypermobility

The new terminology within this spectrum updates terms used to define patients (different types of HSDs,

hEDS

)

Clinical diagnostic criteria without a known molecular cause will, by definition, be imperfect

Definition of

hEDS

may change over time with increasing knowledge of the underlying pathophysiology of symptomatic joint hypermobility

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Future directions

Stringent application of criteria will allow for more standardized classification and phenotyping of patients with EDSCreation of patient registries may become more useful in delineating risk factors for EDS co-morbidities and set the groundwork for evidence-based treatment modalitiesMolecular studies can be more efficiently completed on more homogeneous sub-groups of patientsDiscovery of other subtypes of EDS may lead to a better understanding of common pathologic features

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Studying efficacy of interventions: ++Need for randomized control trials

Pain management

: Utility of earlier diagnosis and preventative measures for pain, research on use of NSAIDs in the context of increased bleeding, Oxygen therapy, Studies into proprioceptive impairment and treatment, low dose naltrexone

Psychiatric

: Efficacy of psychiatric and psychological approaches (CBT dealing with dysfunctional coping, pharmacologic treatment)

Gastrointestinal

:

aetiology

of GI symptoms in

hEDS

require further clarification, elucidating precipitating factors for GI problems in EDS

Orthopedic

: Efficacy of surgical interventions vs. conservative

mgt

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Studying efficacy of interventions: Need for randomized control trials

Physical Therapy:

Use of strengthening programs, orthotics, exercises of proprioception/balance, taping, hydrotherapy

Cardiovascular:

Prevalence of autonomic dysfunction, efficacy of treatments

Neurosurgical:

Studies in risks of shunting, stenting for IIH,

prospective studies on outcomes for

chiari

malformation treatment, utility of dynamic imaging studies to dx AAI, long term studies on surgical outcomes for treatment of instability, determine clinical criteria for TCS in

hEDS

, incidence of TCS, surgical outcomes, investigations on treatment of

tarlov

cysts

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Other areas of research

Prevalence and treatment of Gynecological/Obstetric issues in EDS

Determine evidence for best practice in medical surveillance and surgical intervention in vascular EDS

Improvement in patient outcomes given educational interventions to health care practitioners

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In summary

2017 update in classification of EDS has not fully addressed ongoing questions regarding pathophysiology and management of

hEDS

and HSDs

Aim is for increased homogeneity of groups leading to a possible molecular diagnosis and better studies to elucidate treatments

Revision of current criteria may be necessary once molecular pathophysiology further elucidated and natural history of HSDs and

hEDS

examined over time