Classical Ehlers-Danlos Syndrome ClairA.Francomano,MD
EDSCenterforClinicalCareandResearchHarveyIns>tuteforHumanGene>csGreaterBal>moreMedicalCenter
Commi5ee Members
• JessicaM.Bowen• GlendaJ.Sobey• NigelP.Burrows• MarinaColumbi
• MarkLavallee• FransiskaMalfait• Chris>naSchwar>ng• ClairA.Francomano
Classical EDS: History
• Beighton,1968:EDSGravisandMi>s• Beighton,1988:EDSTypesIandII• Villefranchenosology,1997:ClassicalEDS
• 1996:Iden>fica>onofmuta>onsinCOL5A1(Nichollsetal.,1996;Wenstrupetal.,1996;DePaepeetal.,1997)
Recommended Naming
• Retainthename“ClassicalEhlers-DanlosSyndrome”• Abbrevia>on:cEDS
Proposed Diagnos@c Criteria
Majorcriteria1.Skinhyperextensibilityandatrophicscarring2.Jointhypermobility
Minor Diagnos@c Criteria
1.Easybruising2.So`,doughyskin3.Skinfragility(ortrauma>csplibng)4.Molluscoidpseudotumours5.Subcutaneousspheroids6.Hernia(orhistorythereof)7.Epicanthalfolds8.Familyhistoryofafirstdegreerela>vewhomeetsclinicalcriteria
To Establish a Clinical Diagnosis
MajorCriterion(1):SkinhyperextensibilityandatrophicscarringPlus• Either:Majorcriteria(2)–jointhypermobility• Or:threeoftheeightminorcriteria
Clinical considera@ons
Skinisconsideredhyperextensibleifitcanbestretchedoverastandardizedcutoffinthreeofthefollowingareas• 1.5cmforthedistalpartoftheforearmsandthedorsumofthehands• 3cmforneck,elbowandknees
Skin Hyperextensibility
Scarring
• Abnormalscarringcanrangeinseverity.• Mostpa>entshaveextensiveatrophicscarsatanumberofsites.• Thesecansome>mesbehaemosidero>c.• Aminorityofpa>entsaremoremildlyaffected.
Scarring
Joint Hypermobility
• JointhypermobilityisassessedthroughtheBeightonscore.Ascoreof5ormoreisconsideredposi>veforthepresenceofjointlaxity
Beighton Scale
Clinical Considera@ons (2)
• Easybruisingcanoccuranywhereonthebody,includingunusualsites.• Thepre>bialareao`enremainsstainedwithhemosiderinfrompreviousbruises
Bruising
• Subjec>veabnormalityoftheskintextureisappreciableonexam
• Molluscoidpseudotumorsarefleshylesionsassociatedwithscars,foundoverpressurepoints(e.g.elbow,fingers)
Molluscoid Pseudotumors
Clinical Considera@ons (3)
• Subcutaneousspheroidsaresmallsphericalhardbodies,frequentlymobileandpalpableontheforearmsandshins.Spheroidsmaybecalcifiedanddetectableradiologically• Epicanthalfoldsareo`enseeninchildhoodbutmayalsobeseeninadults.
Verifica@on of Clinical Diagnosis
• Confirmatoryanalysisisrecommendedforanypa>entmee>ngtherecommendedclinicalcriteria.• MolecularanalysisofCOL5A1andCOL5A2genesiden>fiesacausalmuta>oninmorethan90%ofthepa>entsandshouldbeusedasthestandardconfirmatorytest.• Incaseofunavailabilityofgene>ctes>ng,electronmicroscopyfindingsofcollagenflowersonskinbiopsycansupporttheclinicaldiagnosis.• Absenceoftheseconfirmatoryfindingsdoesnotexcludethediagnosis,howeveralterna>vediagnosesshouldbeconsideredintheabsenceofatypeVcollagengenemuta>onorelectronmicroscopyfindings.
HUMANMUTATION,Vol.33,No.10,1485–1493,2012
Organ System Review
• Musculoskeletal• Skin• Cardiovascular• Gastrointes>nal• Neurologic
Musculoskeletal
• Jointhypermobility• Complica>onsofjointhypermobility• Mildmusclehypotonia• Skeletalmorphologyaltera>ons• Increasedbonefragility(osteopeniaorosteoporosis)
Skin
• Stretchy• So`• Severeatrophicscarring• Hemosidericscarsovertheshinsandextensorsurfacesoftheforearm• Easybruising
Cardiovascular
• Aor>crootdila>on;rarelyprogresses• Mitralvalveprolapse• Venousinsufficiency
Gastrointes@nal
• Dysphagia• Dyspepsia• Gastro-esophagealreflux• Hiatalhernia• Irritablebowelsyndrome• Unspecifiedabdominalpain• Cons>pa>on• Diarrhea• Rectocoele
Neurologic
• Pain• Dysautonomia• Headache• FrequencyofChiariI,craniocervicalinstability,tetheredcordasyetundefined.
Others
• Prolongedbleeding>me• Chronicfa>guesyndrome• Mastcellac>va>on• Giantbladderdiver>culi
Management - Skin
• Avoidanceoftrauma• Closureofwounds–plas>csurgeonifpossible• Ascorbicacid(2gm/dayforadults)• DDAVPmayhelptonormalizebleeding>me• Avoidexcessivesunexposure
Management - Muscloskeletal
• Physiotherapy• Avoidhigh-impactac>vi>es• Avoidexcessivedemonstra>onsofhypermobility• Amul>-disciplinaryteamisveryhelpfulformanagement• Ringsplints,carefullyconsideredbracingandortho>csmaybehelpful• DEXAanalysis
Management – Pain
• Neurologicalassessmentinpa>entswithsymptomssugges>veofneuropathicpain/compressionneuropathy• Regular,light,non-weight-bearingexercise.• Physicaltherapyformusclerelaxa>onandmyofascialtriggerpointrelease• Relaxa>ontechniquesincludingmindfulness-basedstressreduc>onandbiofeedback• Counsellingsupportincludingcogni>vebehaviouraltherapy• An>-inflammatorydrugsandpainmedica>ons
Management - Cardiac
• Echocardiographytolookforaor>crootdila>onandmitralvalveprolapse.• Aor>crootsizeandmitralvalveprolapseareincreasedinpa>entswithclassicalEDS,buttheytendtobeoflioleclinicalsignificance.• Echofrequencyinsymptom-freeadultsfrequencycanbereduced(Atzingeretal.,2011).• Ifechoisnormalinadulthoodnofollowupisrequired(Malfaitetal.,2010).• Considervascularimaging/agreessivebloodpressurecontrolifthepa>enthasaglycinesubs>tu>oniden>fiedneartheC-terminalendofthetriplehelix,oronthebasisoftheirfamilyhistory(Monroeetal.,2015)
Management - Gastrointes@nal
• Uppergastrointes>nalendoscopyor24hpH-metrytoevaluaterefluxdiseaseinsymptoma>cpa>ents.Treatmentwithproton-pumpinhibitorifneeded• Colonoscopyshouldbeperformedwithcareduetoapossiblyincreasedriskofmucosalbleeding• Treatmentoffunc>onalgastrointes>nalcomplaintsinEDSpa>entsisproblema>cduetotheabsenceoftailoredstrategiesandanapparentresistancetopharmacologictreatmentsatstandarddosages/regimens.• Pa>enteduca>on,alsocomprisingdietandnutri>onaladvice,seemsatthemomentthemosteffec>vemanagementtool
Management - Pregnancy
• Followupthroughoutpregnancyiswarranted.• Prematurityhappensmoreo`enwhenthefetusisaffectedandismainlyduetoprematureruptureofthemembranes• Breechpresenta>onismorecommonifthebabyisaffected,duetohypotonia
Differen@al Diagnosis
• Cardiac-valvulartypeEDS• TenascinXdeficientEDS• Spondylocheirodysplas>ctypeEDS• LoeysDietzsyndrome• OI/EDSoverlapsyndrome
Thanks
• TheClassicalEDScommioee• Ourpa>entsandtheirfamilies• TheEhlers-DanlosSocietyandEDS-UK• LaraBloomandShaneRobinson
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