Multiple pilomatricomas in twins with Rubinstein-Taybi syndrome,

AnBrasDermatol.2020;95(5):619---622

Anais

Brasileiros

de

Dermatologia

CASE

REPORT

Multiple

pilomatricomas

in

twins

with

Rubinstein-Taybi

syndrome

夽,夽夽

Ana

Laura

Andrade

Bueno

_,

_Maria

_Emilia

_Vieira

_de

_Souza

_,

Carla

Graziadio

_,

_Ana

_Elisa

_Kiszewski

a_{DermatologyService,UniversidadeFederaldeCiênciasdaSaúdedePortoAlegre,PortoAlegre,RS,Brazil} b_{IrmandadedaSantaCasadeMisericórdiadePortoAlegre,PortoAlegre,RS,Brazil}

c_{DisciplineofClinicalGenetics,UniversidadeFederaldeCiênciasdaSaúdedePortoAlegre,PortoAlegre,RS,Brazil}

d_{PediatricDermatologyUnit,DermatologyService,UniversidadeFederaldeCiênciasdaSaúdedePortoAlegre,PortoAlegre,RS,}

Brazil

Received14December2019;accepted5March2020

Availableonline15July2020

KEYWORDS

Pilomatrixoma; Pilomatricoma; Rubinstein-Taybi syndrome; Tumoroftheskin appendages

Abstract Pilomatricomasarebenigntumorsoriginatingfromthecapillarymatrix,whichmay

presentassolitarylesionsor,lesscommonly,multiple.Myotonicdystrophyandfamilial

adeno-matouspolyposisarethemostfrequentlyassociateddisorderswithmultiplepilomatricomas.

Therearefewreportsrelatingthesetumorstoothergeneticsyndromes.Rubinstein-Taybi

syn-dromeisarareautosomaldominantdisordercharacterizedbyintellectualdisabilityandtypical

dysmorphiccharacteristics.Therearefivecasereportsrelatingtomultiplepilomatricomato

Rubinstein-Taybisyndrome,anassociationthatneedstobeclarified.Forthisreason,wereport

the first caseofmultiplepilomatricoma inmonozygotic twinswith typicalRubinstein-Taybi

syndrome.

©2020SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan

openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

夽 _{Howto citethisarticle: BuenoALA,SouzaMEV,GraziadioC,} Kiszewski AE. Multiple pilomatricomas in twins with Rubinstein-Taybisyndrome.AnBrasDermatol.2020;95:619---22.

夽夽_{Study conducted at the Dermatology Service, Universidade} FederaldeCiênciasdaSaúdedePortoAlegreandPediatric Derma-tologyUnit,HospitaldaCrianc¸aSantoAntonio,IrmandadedaSanta CasadeMisericórdiadePortoAlegre,PortoAlegre,RS,Brazil.

∗_{Correspondingauthor.}

E-mail:kiszewski@gmail.com(A.E.Kiszewski).

Introduction

Pilomatricomasareuncommonbenigntumorsderivedfrom hairmatrix.Theymainlyaffectthepediatricpopulationand aremore frequentlylocated on thehead andneck. They presentclinicallyasnoduleswithfirmorstonyconsistency, circumscribed,normochromic,orerythematous,whichcan be confused with epidermal cysts. Although they usually presentassolitarylesions,multiplepilomatricomascanbe observedin2.4%to5%ofcases.1---3

https://doi.org/10.1016/j.abd.2020.03.011

0365-0596/©2020SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).

620 BuenoALAetal. Multiple pilomatricomas can be sporadic, familial, or

associatedwithan underlyingsyndrome. Myotonic dystro-phyandfamilialadenomatouspolyposis(FAP)arethemost frequentlyassociateddisorderswithmultiple pilomatrico-mas.Therearesporadicreportsoftheassociationofthese tumors with Turner, Kabuki, Sotos, and Rubinstein-Taybi syndromes.2

Rubinstein-Taybi Syndrome (RTS) is a rare autosomal dominant genetic disorder, characterized by postnatal growthretardation,moderatetosevereintellectual disabil-ity,andawiderangeoftypicaldysmorphiccharacteristics. Broad, angled thumbs and halluces are a distinguish-ing feature of the syndrome. Facial anomalies include slantedeyelidslits,highandelongatednasalpyramid,and micrognathia. Cardiac malformations, dental alterations, andcryptorchidismarecommon.4 _{The most common}

der-matologicalfindings include hemangiomas,hypertrichosis, brachyonychia,andatendencytokeloidformation.1

Althoughapproximately60%ofcasesareassociatedwith mutationsintheCREBBPorEP300genes,theetiologyofRTS isheterogeneousandpoorlydefined.1,5

There arefewcases describing theassociation of pilo-matricomas with RTS, and it is not clear whether this associationisduetochance.6_{Accordingtoarecentreview}

ofthe literature,nine caseshave been reportedthus far, andfiveofthem presentedmultiple lesions.2_{The authors}

reportthefirstcaseofmultiplepilomatricomasin monozy-gotictwinswithtypicalRTS.

Case

reports

Monozygotic twins, 8 years old, with delayed neuropsy-chomotor development, oblique eyelid clefts, discrete micrognathia, ogival palate, prominent auricular helix, nipple hypertelorism, and mild hypertrichosis on the dor-sal spine and shoulders. Both had a previous history of cryptorchidism and of short, wide thumbs, whose radial deviation had been surgically corrected. Twin 1 had undergone cardiac surgery to correct interventricu-larcommunicationandhadaprevioushistoryofoccipital, frontal,andsupramammaryhemangiomas,whichhad spon-taneously regressed (Fig. 1). Twin 2 presented cerebral aqueduct stenosis and polydactyly, also previously cor-rected. The karyotype examination of both patients was normal(46,XY)and,inlightofthetypicalphenotypic find-ings,theywerediagnosedwithRTSbythegeneticsteam.

At a dermatological consultation, twin 1 presented a normal, asymptomatic nodular lesion in the left scapular region.An ultrasonographywasperformed, whichshowed anechogenic nodularimage,emittingaposterior acoustic shadow, measuring1.4cm in its largest diameter. In sub-sequent consultations, over a period of two years, both patientsdevelopedmultiple similarnodularlesionsonthe scalp(totaloffivelesionsintwin1andfourintwin2).Twoof themwereexcised,onelocatedonthescalpandtheother onthescapularregion(Fig.2),bothshowinghistologicallya nodularproliferationcomposedofbasaloidmatrixcellsand phantomcells(Figs.3and4),findingsthatwerecompatible withthediagnosisofpilomatricomas.Theremaininglesions wereclinicallyfollowed-up.Thepatientshadnofamily his-toryofpilomatricomas.

Figure1 Twin1withslanting eyelidslits,discrete

microg-nathia, prominent auricular helices, nipple hypertelorism,

sternalscarsecondarytocardiacsurgerytocorrect

interven-tricularcommunication,widethumbsandradialdeviation.

Discussion

Pilomatricomasareusuallybenignsolitarylesions.However, thesetumorscanpresentasmultiplelesionsand,although they can occur in healthy individuals, it is recommended tocollectadetailedfamilyhistoryand discardassociated syndromes.7

Myotonic dystrophy and FAP are the syndromes most related to multiple pilomatricomas. The association betweenRTSandpilomatricomaswasfirstpublishedin19946

MultiplepilomatricomasinRubinstein-Taybisyndrome 621

Figure2 Normochromicnodular lesion intheleft scapular

region which was excised. Mild hypertrichosis on the dorsal

spineandshoulders.

Figure3 Anatomopathologicalaspect:nodularproliferation

composedofbasaloidmatrixcellsandghostcells(Hematoxylin

&eosin,×10).

However,only fiveofthesecasesrelatedmultiple piloma-tricomastothesyndrome.2

A2019reviewofthesyndromesassociatedwithmultiple pilomatricomasfoundthatnon-syndromicpatientstendto havefewerpilomatricomaswhencomparedwithsyndromic patients.2 _{While4.5% of non-syndromic individuals}

devel-oped more than five pilomatricomas, 46.3% of syndromic patientsdevelopedsixormoretumors.However,although therelationshipbetween multiplepilomatricomasandthe

Figure4 Anatomopathologicalaspect:nodularproliferation

composedofbasaloidmatrixcellsandghostcells(Hematoxylin

&eosin,×40).

underlyingsyndromestrengthensasthenumberof piloma-tricomasincreases,somesyndromesmayhaveonlyoneor twolesions.2 _{The review of the RTScasesdescribed until}

2019showedthatthenumberofpilomatricomasassociated withthis syndrome is quite varied. From a total of nine cases,fourcaseshadtwotofivepilomatricomas,onehad morethan10andfourhadsolitarypilomatricomas.1,2,5,6,8---10

Furthermore,aseriesoffourcasespublishedin1998showed that,inthisgroupofpatients,themeanageoftumoronset was not earlier than in healthy patients, in whom most lesionsappearbetweentheagesof8monthsand10years.9

TheetiologyofpilomatricomainRTShasyettobe elu-cidated.Mutationsintwogenes,CREBBPandEP300,have been observed in affected individuals and both encode homologousproteinsthatactastranscriptionco-activators. Duringorganogenesis,CREBBPis expressedin specificcell typesofthedevelopingheart,vasculature,skin,lungs,and liver.In2016,thefirstcaseofRTSwithmultiple pilomatrico-masdiagnosedbyCREBBPmutationanalysiswasreported. However,thecorrelationbetweentheCREBBPgenotypeand theonsetofmultiplepilomatricomasstillneedstobe clar-ified, since thereare also case reports that describe the CREBBPmutationinpatientswithRTSwithout pilomatrico-masorwithasolitarylesion.5

DataonpilomatricomasinRTSarestilllimitedtosome casereports.Intheliteraturereview.Thisisthefirstreport of multiple pilomatricomas in twins withRTS, reinforcing the association between thesetwo entities. The molecu-lar mechanisms that lead patients with RTSto a greater susceptibilitytopilomatricomaswarrantsfurtherstudies.

Insomecases,thedetectionofpilomatricomasmayoffer an opportunity for the diagnosis of RTS. The therapeutic approachtomultiplelesionsinRTSisyettobeestablished. Inthepatientspresented,aconservativeapproachwas cho-sen,andtheyarebeingfollowed-upwithoutintervention.

Financial

support

622 BuenoALAetal.

Authors’

contributions

Ana Laura Andrade Bueno: Approval of the final ver-sion of the manuscript; conception and planning of the study;elaborationandwritingofthemanuscript;obtaining, analyzing, and interpreting the data; effective participa-tion in research orientation; intellectual participation in propaedeuticand/ortherapeuticconductofstudiedcases; critical review of the literature; critical review of the manuscript.

MariaEmiliaVieiradeSouza:Approval ofthefinal ver-sion of the manuscript; conception and planning of the study;elaborationandwritingofthemanuscript;obtaining, analyzing,andinterpretingthedata;intellectual participa-tioninpropaedeuticand/ortherapeuticconductofstudied cases;criticalreviewoftheliterature;criticalreviewofthe manuscript.

Carla Graziadio: Approval of the final version of the manuscript;conceptionandplanningofthestudy; elabora-tionandwritingofthemanuscript;obtaining,analyzing,and interpretingthedata;effectiveparticipationinresearch ori-entation;intellectualparticipationinpropaedeuticand/or therapeuticconductofstudiedcases;criticalreviewofthe literature;criticalreviewofthemanuscript.

AnaElisaKiszewski:Approvalofthefinalversionofthe manuscript;conceptionandplanningofthestudy; elabora-tionandwritingofthemanuscript;obtaining,analyzing,and interpretingthedata;effectiveparticipationinresearch ori-entation;intellectualparticipationinpropaedeuticand/or therapeuticconductofstudiedcases;criticalreviewofthe literature;criticalreviewofthemanuscript.

Conflicts

of

interest

AnaLauraAndradeBueno,MariaEmiliaVieiradeSouza,and CarlaGraziadiodeclaretohavenoconflictofinterest.Ana

ElisaKiszewskideclarestohave aconflictofinterestwith thecompanyJohnson&Johnson.

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2.Ciriacks K, Knabel D, Waite MB. Syndromes associated with multiplepilomatricomas:Whenshouldcliniciansbeconcerned? PediatrDermatol.2020;37:9---17.

3.Danielson-CohenA, LinSJ,HughesCA,AnYH,MaddalozzoJ. Head and neck pilomatrixoma in children. Arch Otolaryngol HeadNeckSurg.2001;127:1481---3.

4.Pérez-Grijalba V, García-Oguiza A, López M, Armstrong J, García-Mi˜naur S, Mesa-Latorre JM, et al. New insights into geneticvariantspectrumandgenotype-phenotypecorrelations ofRubinstein-Taybisyndrome in39CREBBP-positivepatients. MolGenetGenomicMed.2019;7:e972.

5.RokunoheD,NakanoH,AkasakaE,ToyomakiY,SawamuraD. Rubinstein-Taybisyndromewithmultiplepilomatricomas:The firstcasediagnosedbyCREBBPmutationanalysis.JDermatol Sci.2016;83:240---2.

6.CambiaghiS,ErmacoraE,BrusascoA,CanziL,CaputoR. Multi-plepilomatricomasinRubinstein-Taybisyndrome:acasereport. PediatrDermatol.1994;11:21---5.

7.KingIC,RahmanKM,HendersonA,RagbirM.Multiplefamilial pilomatrixomasin threegenerations:anunusualclinical pic-ture.PediatrDermatol.2015;32:97---101.

8.BayleP,BazexJ,LamantL,LauqueD,DurieuC,AlbesB. Multi-pleperforatingandnonperforatingpilomatricomasinapatient withChurg-StrausssyndromeandRubinstein-Taybisyndrome.J EurAcadDermatolVenereol.2004;18:607---10.

9.MasunoM,ImaizumiK,IshiiT,KurokiY,BabaN,TanakaY. Pilo-matrixomas in Rubinstein-Taybisyndrome. AmJ MedGenet. 1998;77:81---2.

10.YagiY,KuwatsukaY,AsaiM,HondaM,UtaniA.Coexistenceof keloidsand pilomatricomainapatientwithRubinstein-Taybi syndrome.DermatolOnlineJ.2018;24,pii:13030/qt4rq2k5fr.