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ACaseofAntleyBixlerSyndrome

JClinNeonatol.2012JanMar1(1):4648.

PMCID:PMC3761981

doi:10.4103/22494847.92232

ACaseofAntleyBixlerSyndrome
SubhrajitLahiri,BhaswatiGhoshal,andDebabrataNandi
DepartmentofPediatrics,CalcuttaNationalMedicalCollegeandHospital,Kolkata,WestBengal,India
rd
Addressforcorrespondence:Dr.SubhrajitLahiri,3 Floor7,PrinceGolamMohammedRoad,Kolkata700026,WestBengal,India.E
mail:subhrajitlahiri@ymail.com
Copyright:JournalofClinicalNeonatology
ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionNoncommercialShareAlike3.0Unported,which
permitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.

Abstract
AntleyBixlersyndrome(ABS)israreformofcraniosynostosisofbothautosomaldominantandautosomal
recessiveinheritance.Wearereportingafemaletermappropriateforgestationalagenewbornwithclinical
featuresoffrontalbossing,brachycephaly,proptosis,synostosisofradioulnarjoints,hemangiomaovernose
andphiltrum,hydrocephalussuggestiveofABS.
Keywords:AntleyBixlersyndrome,craniosynostosis,proptosis
INTRODUCTION
Firstdescribedin1975,[1]AntleyBixlersyndrome(ABS)isanautosomalrecessive,exceptionallyrare
craniosynostosissyndromecharacterizedbyradiohumeralsynostosispresentfromtheperinatalperiod
(OMIMnumber#207410).Only50caseshavebeenreportedyet.[2]Thereisawidespectrumofanomalies
seeninABSotherfeaturesincludemidfacehypoplasia,choanalstenosisoratresia,andmultiplejoint
contractures.Mortalityhasbeenreportedtobeashighas80%intheneonatalperiod,primarilyduetoairway
compromise,andprognosisimproveswithincreasingage.[3]
CASEREPORT
Afulltermappropriateforgestationalage(AGA)femalebabywasbornofnonconsanguineousmarriageof
aprimiparousmotherbycaesareansection.Birthweightwas2.5kg.Thenewborncriedatbirth.Motherhad
anuneventfulpregnancy.Therewasnohistoryofintakeoffluconazoleduringthepregnancy.Therewasno
historyofobviouscongenitalanomaliesorfetallossinthefamily.Onexamination,vitalswerestable.Baby
hasnormalreflexesandsucksmother'smilkwell.Craniofacialabnormalitiesfoundwerebrachycephaly
(cephalicindex=95.45),frontalbossing,largeanteriorfontanel,openmetopicsuture,synostosisinsagittal
andlambdoidsutures,deficientskullbonesoverbothtemporalfosse,proptosisofrighteyewithopacityof
cornea,lefteyeprominentwithrednessofconjunctiva,lowsetears,higharchedpalate,choanalstenosis,
bilateralstenoticexternalauditorycanal,shortneck,hemangiomaovernoseandphiltrum,anddepressed
nasalbridge.Interpupillarydistance=5.5cm(>90thpercentile),Headcircumference=32.5cm(2550th
percentiles).Limbdefectswereradioulnarsynostosisleadingtofixedflexiondeformityofelbowjoints,fixed
flexiondeformityofboththumbsinproximalanddistalinterphalangealjoints,arachnodactyly,rockerbottom
feet,halluxvarus,kneeandhipjointcontracture.Otherabnormalitieswereprominentchest,femalegenitalia
withhypoplasticlabiamajora[Figure1].
SepsisscreenwaspositiveondayfourandbloodculturerevealedlateonsetsepsisbyStaphylococcus
aureus.17AlphaHydroxyprogesteronewasfoundtobenormalat10ng/dl.Thereisnohistorysuggestive
ofadrenalinsufficiency.Radiologicalinvestigationsshowedradioulnarsynostosisandarachnodactyly.[
Figure2]Ultrasonography(USG)ofbrainrevealedventriculardilatation.USGofabdomenwasnormal.
Brainimagingrevealedhydrocephalousofobstructivetypewiththickenedfourthventricle.Basalcisternsare
normal.Echocardiographywasnormal.Patienthadthreeepisodesofapneaduringthehospitalstay.The
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babyreceivedgentamicinandciprofloxacin(asperculturesensitivity)forlateonsetsepsisfor14days.
AbovefeaturessuggestABS.However,therewerenoenlargedinterphalangealjointsorincreasedfemoral
bowingorfractures.Atpresent,babyisonexclusivebreastfeeding.Nofurtherepisodeofapneawas
noticedafterfirstsevendays.Occasionalnasalobstructionneedstreatmentwithsalinenasaldrops.
Enucleationofeyehasbeenplanned.
DISCUSSION
AntleyandBixler(1975)describedachildwithtrapezoidocephaly,midfacehypoplasia,humeroradial
synostosis,bowingoffemora,fractures,andotherabnormalities.[2]Crisponietal.(1997)statedthatsince
thefirstreportbyAntleyandBixler(1975)atleast23caseshadbeenreported.Theyreportedanaffected
infantwhodiedafewdaysafterbirthofrespiratoryfailure.Unlikepreviouslydescribedcases,theelbow
jointcontracturesinourpatientwereduetoradioulnarsynostosisratherthanradiohumeralsynostosis.The
infantdidnothavelongbonefractures,andthefemurswerenotmarkedlybowed.[4]Ourcasealsodidnot
havelongbonefractureorbowingoffemur.Chunetal.(1998)reportedapatientwithclinical
manifestationsthattheyconsideredconsistentwithABSwhocarriedanser351tocysmutationononeallele
ofthefibroblastgrowthfactorreceptor2(FGFR2)gene.[5]Chunetal.(1998)suggestedthattheABSisan
autosomaldominantconditionwithpossiblegonadalmosaicism,orthatalternatively,anautosomaldominant
formandanautosomalrecessiveformofABSmayexist.However,nogeneticstudycouldbearrangedfor
ourpatient.MutationsinthegenesforFGFRhavebeenreportedtobeinvolvedinsomecraniosynostosis
syndromessuchasPfeiffer,Apert,Cruzon,andJacksonWeissSyndromes.Mutationsinthecytochrome
P450oxidoreductasegene(POR)locatedonchromosome7q11.23resultinautosomalrecessiveinheritance
andanABSphenotypethatincludesgenitalambiguityandcharacteristicurinarysteroidprofile.[6]Inutero
exposuretofluconazole[1]maybeareason.DigenicinheritancewhereFGFR2mutationsaccountforthe
skeletalabnormalitiesanddifferentmutationscausingalteredsteroidogenesiscontributetothegenital
anomalies.[1]Lehuepetal.(1995)reportedtwoaffectedsibs,[7]inthefirstcase,renalagenesiswas
recognizedprenatallywhenoligohydramniosledtothesonographicdiagnosisofabsentkidneysduringthe
seventhmonth.Clinicalfeatureswererecognizedbyultrasonographyat21weeksinthesecondcase.
However,nosuchfindingswerepresentinourpatient.Undetectableunconjugatedestriolimplyingabnormal
fetalsteroidorsterolmetabolismhasbeendemonstratedatmidgestationalmaternalserumscreeningand
mayprovideaprenatalmarkerforthisdisorderinsomecases.[8]McGlaughlinetal.(2010)notedthat
craniosynostosisandradiohumeralsynostosispresentfromtheperinatalperiodaregenerallyconsideredtobe
theminimumcriteriaforadiagnosisofABS,[3]thushelpingustodiagnosethecase.Respiratory
compromisesecondarytoupperairwayobstructionvariesfromseverenasalcongestiontomultipleapneic
episodesleadingtodeathinthefirstfewmonthsoflife.[1]Ourpatientalreadyhadthreeepisodesofapnea
andreceivessalinenasaldropsfornasalcongestion.Infuture,shemayneedtracheostomyorplacementof
gastrostomytube.Prognosisofthediseaseisgoodoncetheperinatalperiodhaspassed.Jointcontractures
haveimprovedwithageandpassiverangeofmotionexercises.Therehasbeennopropensitytofracture
postnatally.[1]Inourpatient,wehaveplannedenucleationoftherighteye.Lefteyeisnormal.Infuture,we
mayattemptresectionoftheradiohumeraljoint.Weshallfollowupthepatientfrequentlyforearlydiagnosis
andtreatmentofthecomplicationsandmonitorneurodevelopmentaloutcome.
Footnotes
SourceofSupport:Nil
ConflictofInterest:Nonedeclared.

REFERENCES
1.AntleyR,BixlerD.Trapezoidocephaly,midfacehypoplasiaandcartilageabnormalitieswithmultiple
synostosesandskeletalfractures.BirthDefectsOrigArticSer.197511:397401.[PubMed:1227559]
2.JonesKL.Smith'srecognizablepatternsofhumanmalformation.6thed.Noida:Elsevier2006.
Craniosynostosissyndromespp.48891.
3.McGlaughlinKL,WitherowH,DunawayDJ,DavidDJ,AndersonPJ.SpectrumofAntleyBixler
syndrome.JCraniofacSurg.201021:15604.[PubMed:20818252]
4.CrisponiG,PorcuC,PiuME.AntleyBixlersyndrome:Casereportandreviewoftheliterature.Clin
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Dysmorph.19976:618.[PubMed:9018420]
5.ChunK,SiegelBarteltJ,ChitayatD,PhillipsJ,RayPN.FGFR2mutationassociatedwithclinical
manifestationsconsistentwithAntleyBixlersyndrome.AmJMedGenet.199877:21924.
[PubMed:9605588]
6.HuangN,PandeyAV,AgrawalV,ReardonW,LapunzinaPD,MowatD,etal.Diversityandfunctionof
mutationsinP450oxidoreductaseinpatientswithAntleyBixlersyndromeanddisorderedsteroidogenesis.
AmJHumGenet.200576:72949.[PMCID:PMC1199364][PubMed:15793702]
7.LeHeupBP,MasuttiJP,DroullP,TisserandJ.TheAntleyBixlersyndrome:Reportoftwofamilialcases
withsevererenalandanalanomalies.EurJPediatr.1995154:1303.[PubMed:7720741]
8.CragunDL,TrumpySK,ShackletonCH,KelleyRI,LeslieND,MulrooneyNP,etal.Undetectable
maternalserumuE3andpostnatalabnormalsterolandsteroidmetabolisminAntleyBixlersyndrome.AmJ
MedGenetA.2004129:17.[PubMed:15266606]
FiguresandTables
Figure1

ThepictureofthebabywithAntleyBixlerSyndrome
Figure2

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Xrayshowingradioulnarsynostosis
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