Rev. Bras. Reumatol. vol.56 número1

rev bras reumatol.2016;56(1):86–89

w w w . r e u m a t o l o g i a . c o m . b r

REVISTA

BRASILEIRA

DE

REUMATOLOGIA

Case

report

Skeletal

abnormalities

of

tricho-rhino-phalangeal

syndrome

type

I

Guilherme

Monteiro

de

Barros,

Adriana

Maria

Kakehasi

UniversidadeFederaldeMinasGerais,BeloHorizonte,BeloHorizonte,MG,Brazil

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Articlehistory:

Received24April2014 Accepted26August2014 Availableonline9March2015

Keywords:

Tricho-rhino-phalangealsyndrome typeI

Jointmalformations Geneticsyndrome

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Thetricho-rhino-phalangealsyndrome(TRPS)typeIisararegeneticdisorderrelatedto theTRPS1genemutationinchromosome8,characterizedbycraniofacialabnormalities and disturbances in formation and maturation of bone matrix. The hallmarks are sparseandbrittlehair,tendencytoprematurebaldness,bulbousnosecalledpear-shaped, longandflatfilterandlowearimplantation.The mostnoticeableskeletalchangesare clinodactyly,phalangealepiphysesofthehandsappearingascone-shaped,shortstature andhipjointmalformations.WereportacaseofateenagerboydiagnosedwithTRPSand referredforrheumatologicevaluationduetojointcomplaints.

©2014ElsevierEditoraLtda.Allrightsreserved.

Anormalidades

esqueléticas

da

síndrome

tricorrinofalangiana

tipo

I

Palavras-chave:

SíndrometricorrinofalangianatipoI Malformac¸õesarticulares

Síndromegenética

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Asíndrometricorrinofalangiana(STRF)tipoI_{éumadoenc¸agenéticarara,relacionadacom} amutac¸ãonogeneTRPS1docromossomo8.Écaracterizadaporanomaliascraniofaciaise distúrbiosnaformac¸ãoematurac¸ãodamatrizóssea.Ascaracterísticassãocabelosralose quebradic¸os,tendênciaàcalvícieprematura,narizbulbosoemformatodepera,filtronasal longoeplanoebaixaimplantac¸ãodasorelhas.Asalterac¸õesesqueléticasmaisnotáveis sãoaclinodactilia,asepífisesdasfalangesdasmãosemformadecone,abaixaestatura easmalformac¸õesnaarticulac¸ãodoquadril.Relata-seocasodeumadolescente diagnos-ticadocomSTRFeencaminhadoparaavaliac¸ãoreumatológicaemdecorrênciadequeixas articulares.

©2014ElsevierEditoraLtda.Todososdireitosreservados.

∗ _{Correspondingauthor.}

E-mail:amkakehasi@gmail.com(A.M.Kakehasi).

http://dx.doi.org/10.1016/j.rbre.2014.08.017

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Introduction

FirstdescribedbyGiedion,thetricho-rhino-phalangeal syn-drome(TRPS)typeIisararediseasecausedbyTRPS1gene haploinsufficiency,whichislocatedinchromosome8.1_This geneisrelatedtodecodingoftranscriptionfactorsinvolvedin regulationofboneperichondriummineralizationand prolif-erationandapoptosisofchondrocytes.TheTRPSisclassified intothreesubtypes:typesIandIIIhavedistinctclinical pre-sentationsaccordingtoTRPS1mutation,differingclinicallyby degreeofmalformations,2_{whiletypeIIhasassociatedmental} retardationandboneexostosesasalandmark.3_Inmostcases thesyndromeisautosomaldominantandmarkedbyshort stature,finehairandalopecia,pear-shapednose,craniofacial andskeletalmalformations,andphalangealjointdeformity. Althoughrare, individualsmay present tothe rheumatolo-gistatdifferentages,bringingdifferentialdiagnosesincluding juvenileidiopathicarthritisandLegg–Calvé–Perthesdisease. Besideschangesofthehandsandfeet,degenerationofthe hipjointmaybeaseriousconsequenceduetothepotential forearlyfunctionalimpairment.Thisgeneticdiseasepresents broadclinicalspectrumandimportantimpactonpatientand family,requiringmultidisciplinaryapproach.

Case

report

A17-year-oldboywasevaluatedwithcomplaintsofchronic paininthehipsandinterphalangealjointsofthehands.In thelast 7months,hip jointpain wasalsoobservedduring sports activities,which ledthe patient formusculoskeletal systemevaluation.Nomorningstiffnessand nosignificant inflammatorysignswerenoted.Therewasnoreportoffever orweightloss.Fiveyearsago,hismotherobservedsymmetric deformityinproximalinterphalangealjointsofhands char-acterizedbylocalswellingandinsidiousmechanicalpain.In 2009,during the investigation ofshort stature,the patient wasdiagnosedwithtricho-rhino-phalangealsyndrometype Ithroughgeneticstudy.Cognitivedevelopmentwasnormal.

Fig.1–Seventeen-year-oldboywithtricho-rhino-phalangealsyndromeshowingfinehair,longphiltrumandbulboustipof thenose(a)andhandshowingincreasedproximalinterphalangealjoints(b).

Physicalexaminationshowedtriangularfacewiththenose elongated(pear-shaped),thepresenceofmediannasolabial grooveandtaperingofthelips,thinhairandprominentjaw, prominenceoftheinterphalangealjointsofthehands,no red-nessorlocalheat(Fig.1).Therewasnopainonmanipulation and no movementlimitation inupperlimbs. Discreetgenu varus,andpainwithlimitationofmovementwereobserved inbothhipjoints.Laboratorytestswereessentiallynormal: erythrocytesedimentationratewas2mm/h,C-reactive pro-tein<6mg/L(referencevalue<8mg/L),antinuclearantibodies andrheumatoidfactornegative,creatinineandbloodcount cellswerealsonormal.Radiographyofthehandsshowedbone dimorphisminthedistalphalanxofthethumbandthemiddle phalanxoftheotherfingers,characterizedbyshorteningand wideningoftheproximalmetaphysisandproximalepiphysis triangularshape(Fig.2).Radiographyofthehipjointsshowed

coxaplanaandmildsubchondralsclerosisintherightfemoral acetabulumwithpreservedjointspace.Magneticresonance imaging(MRI)ruledoutasepticnecrosisofthehipshowing flatteningofthefemoralnecksandlabralhypertrophy. Assess-mentofbonemineraldensity(BMD)and bodycomposition bydual-energyX-rayabsorptiometry(equipmentHologic Dis-covery W)showedlowBMDinlumbarspine(Z-score−2.3)

andlimitrophebonemineralcontendvalue(Z-scoreof−2.0).

Patientandhisfamily receivedsupportaboutthediagnosis andrecommendationsforarticularstructurespreservation.

Discussion

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Fig.2–Handradiographyshowingshorteningandwideningoftheproximalmetaphysisandproximalepiphysistriangular

shape.

TypesIand IIIarethoughttoexistonacommonspectrum resultingfrommutationsoftheTRPS1gene,andare differenti-atedbythedegreeofphenotypicskeletaldeformity.Deletions spanningTRPS1andthedistaladjacentgeneEXTarefoundin TRPStypeII,andalterationsinEXTarethoughttobe respon-sibleforthe mentaldeficienciesandexostosesseeninthis form.Clinodactylydescribesabendorcurvatureofthefifth fingertowardtheadjacentfourthfingerandcanbeanisolated anomalyoritcanoccurinassociationwithgeneticsyndromes likeTRPS.Deformitieslikeirregularlyshortandstubbyhands are frequent. Similar feet involvementcan occur, but in a lesser extent. As inthis case, deformitiesof the hips and pelvissuchascoxaplana,coxamagna,orfindingsresembling Legg–Calvè–Perthesdisease,canbefound.

Historyandphysicalexaminationcansuggestthe diagno-sisespeciallybecauseofcraniofacialandhandsappearancein typicalcases.Imagingroentgenogramsofhands,pelvis,and hipcanbeusefuland,althoughconedepiphysisatthebase ofphalangesistypical,itcanbefoundinotherskeletal dys-plasiasandinalmost5%ofnormalchildrenandteenagers. AnalysisoftheTRPSand EXT genesatthe 8q24locuscan beundertakentoidentifytheresponsiblemutation.6_Inthis indexpatient,therearenoreportsofrelativeswithsimilar condition,andprobablyasporadicmutationwasresponsible, asreportedbyBoothin1981.7_{Therearereportsofcardiacand} neurologicabnormalities8_{butnoneofthemwerefoundinour} patient.Noassociationwithautoimmunediseaseisdescribed andimmunologicallaboratorytestsareessentiallynormal.

Delayed skeletal maturation and early degeneration of the hips are alsodescribed. This case reportconfirms the mainfeaturesofthesyndromeandaddsinformationabout MR imagingand body composition byDXA. Both diagnos-tic methods are helpful tools in evaluation of phenotype characteristics, bringing more information about articular consequencesandgrowthdisturbances.Thecontributionof

MRIresidesinthepossibilityofearlyevaluationofthejoints cartilage status,allowingtheexclusionofother diseasesor complications,suchashipasepticnecrosis.

Low bone mineral density can be another pitfall in youngindividualswithtricho-rhino-phalangealsyndrome.An appropriateevaluationofbonestatusintheyouthcomprises the composite of lumbar spine mineral density and bone mineralcontendbyDXAand,giventheresultsinthiscase, strategiestominimizeunfavorable evolutioncan be imple-mented.Delayedskeletalmaturationcanalsobefollowedby DXAanditisimportanttorememberthattotalbodyand lum-barspinearethesitestobeevaluatedinindividualslessthan 20years.

One ofthe hallmarks ofthe syndrome is its wide vari-etyofclinicalpresentation,whichincludesasimplechange inthephalangestolowbonemineraldensitywithhighrisk offragilityfractures.Besidesmusculoskeletalcare,patients with tricho-rhino-phalangeal syndrome must be followed upforthedevelopmentofendocrineabnormalitiessuchas hypothyroidism,growthhormonedeficiency,andidiopathic hypoglycemia.5

ExperimentalstudieshavepermittedevaluationofTRPS1 specificroleinkidneydevelopment.NewbornmiceTRPS1−/−

have shortened long bones and incompletely formed pha-langealjoints.ItcouldrevealthatTRPS1actsintheBmp7/p38 MAPK/TRPS1 signaling pathway, responsible for mediating theinductionofmesenchymaltoepithelialtransition,which leadstoformationoftubulesandglomeruliandisessential fornormalrenaldevelopment.9

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and,second,thissyndromecanresembleidiopathicjuvenile arthritis,Legg–Calvè–Perthes,orskeletaldysplasia.Thevalue ofearlyevaluationalsoliesinprovidingthepatientandfamily withappropriatesupportandcounselingforfamilyplanning.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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