HypermobilitySpectrumDisordersClairA.Francomano,MD

OnbehalfoftheFrameworkforHypermobilityDisordersCommittee

MARCOCASTORI,BRADTINKLE,HOWARDLEVY,RODNEYGRAHAME,FRANSISKAMALFAIT,ANDALANHAKIM

ConflictsofInterest

• None

HypermobileEhlers-Danlos Syndrome

JointHypermobilitySyndrome

2009:Tinkleetal.

2014:Castori etal.

2017:Castori etal.Frameworkforclassification

ABriefHistoryofJointHypermobilityandHypermobileEhlers-Danlos Syndrome

…thedelineationofasingleentityarisingasthefull-blownexpressionofthephenotypeincommonbetweenEDS-HTandJHSleaveswithoutan“identity”manyindividualswithsymptomaticjointhypermobility(JH)and/orfeaturesofhEDS,whodonotmeetthestrictercriteriaincorporatedinthenewEDSnosology.Theclassificationofsuchcasesrequiresresolution.

Castori etal.2017

AimsoftheFrameworkPaper

• SummarizetheterminologyofJointHypermobilityandrelateddisorders• PresentthedifferenttypesofJointHypermobility,secondarymusculoskeletalmanifestationsandasimplifiedcategorizationofgeneticsyndromesassociatedwithJointHypermobility• ConsiderthespectrumofsecondarymusculoskeletalmanifestationsandrangeofpleiotropicmanifestationsofsyndromesfeaturingJointHypermobility,notingthatthesearetwoseparatedomainsthatonlypartiallyoverlap

RationaleforanEvolutioninThinking

• Nosologydistinguishingpathogenesisandetiologyisthebackgroundforaclassificationaimedatidentifyingmoreeffectivescientific,therapeutic,andhealthcarestrategies

• ManagementJH-relatedmusculoskeletalmanifestationslikelyrequirehomogeneousrehabilitation/treatmentissuessharedbythedifferentgeneticconditions

• ResearchaclearseparationoftheJHsecondarymusculoskeletalmanifestationsfromtheprimarypleiotropicmanifestationsofEDSmayhelpindissecting theintra-familialandinter-individualvariabilityofhEDS forstudiesaimedatdecipheringitsmolecularbasis

DefiningJointHypermobility

• Jointhypermobility(JH)isthetermuniversallyacceptedtodefinethecapabilitythatajoint(oragroupofjoints)hastomove,passivelyand/oractively,beyondnormallimitsalongphysiologicalaxes.• Hence,JHisadescriptorratherthanadiagnosis.• JHmayexistasanisolateddiagnosticfinding,butisoftenafeatureofalargersyndromicdiagnosis• Synonyms:Jointlaxity,hypermobility,hyperlaxity

MeasuringJointHypermobility

• Useprofessionaltools,suchastheorthopedicgoniometer• Followspecificprocedures(e.g.,[Juul-Kristensenetal.,2007])• Comparethemeasuredrangeofmotion(ROM)withnormalparameters.

TypesofJointHypermobility

• Localized:Involvingalimitednumberofjoints(<5)• Peripheral:Involvingprimarilythesmalljointsofthehandsandfeetwithabsenceoflargeandaxialjointinvolvement• General:Jointhypermobilityat>5sites,includinglargeandaxialjoints• Historical:AhistoryofJointHypermobilitywhichisnolongerpresentonexamination

JointHypermobility JointInstability

• Hypermobilejointsmaybeunstable,butjointinstabilityisnotamandatoryconsequenceofjointhypermobility

• Notallunstablejointsarehypermobile

SecondaryManifestationsofJointHypermobility• Jointhypermobilitymaybeasymptomatic• Thereareaseriesofmusculoskeletalsymptomsandcomplicationsthatmaybeinterpretedassecondarymanifestationsofjointhypermobility• Trauma• Chronicpain• Disturbancesofproprioception

“Occasional and recurrentmusculoskeletal pain is aquite common immediatemanifestation of JH as thenatural consequence ofpredisposition to trauma. Thedevelopment of chronic pain issometimes a long-termcomplication of JH.Preliminary studies suggestthe existence of hyperalgesiaas a possible form of painsensitization in patients withEDS and chronic pain.”

OtherMusculoskeletalTraitsAssociatedwithJointHypermobility

• Pesplanus(flexibletype)• Valgusdeformityofhindfeet,hallucesandelbows• Mildtomoderatescoliosis(>7degrees)• Accentuateddorsalkyphosisandlumbarlordosis• Deformationalplagiocephaly• Reductioninbonemass(maybeapleiotropicgeneticeffect)

DefinitionofaSyndrome

“apatternofanomalies,atleastoneofwhichismorphologic,knownorthoughttobecausally(etiologically)related.”

Hennekam etal,2013

ThepresenceofJHincombinationwithsecondarymusculoskeletalanomaliesdoesnotsufficeforthedelineationofageneticsyndrome.Theappellation“syndromewithJH”shouldberestrictedtogeneticconditionsfeaturingJHtogetherwiththeprimaryinvolvementofatleastasecondtissue/structure(e.g.,skininvolvementinclassicalEDSandhEDS)

Castori etal.,2017

GeneticSyndromeswithJointHypermobility

• TheEhlers-Danlos Syndromes• Manyskeletaldysplasias• Marfan Syndrome• Loeys-DietzSyndrome• Hereditarymyopathies• DownSyndromeandotherchromosomalaneupleudies• Andmanyothers

ClassifyingJointHypermobility

• AsymptomaticpersonswithLocalized,PeripheralorGeneralizedJH• LJH• PJH• GJH

• Personswithawell-definedsyndromeassociatedwithJH• PersonswithsymptomaticJHwhodonotmeetdiagnosticcriteriaforanyotherknownhereditarysyndromeassociatedwithJH• TheHypermobilitySpectrumDisorders

TheHypermobilitySpectrumDisorders(HSD)

• JointHypermobilityplusoneormoresecondarymusculoskeletalmanifestationsofjointhypermobility• Overallclinicalpicturedoesnotmeetthediagnosticcriteriaforanyofthesyndromesassociatedwithjointhypermobility• IntendedasalternativelabelsforindividualswithsymptomaticjointhypermobilitywhodonothaveanyoftheraretypesofEDSanddonotmeetthediagnosticcriteriaforhypermobileEDS.• Also intendedtoidentifydiscretesubtypesfillingthefullgapbetweenasymptomaticJHandhEDS.

TheHypermobilitySpectrumDisorders

• GeneralizedHypermobilitySpectrumDisorder– G-HSD• LocalizedHypermobilitySpectrumDisorder– L-HSD• PeripheralHypermobilitySpectrumDisorder- P-HSD• HistoricalHypermobilitySpectrumDisorder– H-HSD

Extra-ArticularDisordersAssociatedwithGeneralizedJointHypermobility

• Orthostatictachycardia(POTS)• Functionalgastrointestinaldisturbances• Pelvicandbladderdysfunction• Anxiety

Anyofthesemaybeseeninpersonswiththehypermobilityspectrumdisordersandshouldberecognizedandtreatedpromptly

Whatdowecalltheseassociateddisorders?

• Thecommitteefeltthatwedonotyethavesufficientevidencetocalltheseextra-articularmanifestationstruepleiotropicfeaturesofgeneralizedjointhypermobility• Therecommendationisthattheybeconsidered“JointHypermobilityassociatedco-morbidities”• Chronicpain- alateconsequenceofJHoraJH-relatedco-morbidity?Thisisstillamatterofdebateandfurtherresearchisneededtoclarify

GeneticBasisofJH,HSDsandhEDS remainsunknown

• Shouldbeahighprioritytargetforfutureresearchendeavors• Willhelpvalidateandrefinetheexistingdiagnosticcriteria• Shouldguidemorerationaleapproachestomanagementandtherapy

Thanks

• MarcoCastori• BradTinkle• HowardLevy• RodneyGrahame• FransiskaMalfait• AlanHakim

• TheEhlers-Danlos SocietyandEDSUK• LaraBloomandShaneRobinson