A CASE OF NON-MOSAIC ISODICENTRIC Y CHROMOSOME IN A MALE PATIENT WITH ADHD
2 3
Dr.NanditaMainiJindal,MD,
1
Dr.MohitSharma,PHD,Dr.NavjotKaurBajwa,MD1AssistantProfessor,DepartmentofBiochemistry,DayanandMedicalCollegeandHospital,Ludhiana-141001,Punjab,India.
2Associate Biotechnologist, Molecular Genetics Laboratory, Dayanand Medical College and Hospital, Ludhiana-141001, Punjab, India.
3ProfessorandHead,DepartmentofBiochemistry,DayanandMedicalCollegeandHospital,Ludhiana-141001,Punjab,India.
ABSTRACT
CaseDescription:
Conclusion:Thisisararecaseofnon-mosaicisodicentricYchromosomeseeninaphenotypicallynormalmalepatientwithADHD.
KEYWORDS:ADHD,Ychromosome,Isodicentricchromosome,Karyotype.
BACKGROUND:
Attentiondeficithyperactivitydisorder(ADHD)isaneurologicaldevelopmental disorder amongst children and adolescents. The common features include hyperactivity,impulsivity,attentiondeficit,poorinterpersonalrelationshipsand easydistractibilitythatresultsinpoorperformanceinacademics.Prevalenceof ADHDamongIndianpopulationhasbeenfoundtobe7.1%.Theincidencewas foundtobemoreinmales(9.4%)thanfemales(5.2%). ThisformsaconsiderableburdenofADHDinIndianpopulation.
Sex chromosomes are relatively rarely associated with behavioural disorders. IsodicentricYchromosomeisacommonstructuralanomalyofYchromosome encounteredininfertilemalesandrarelyassociatedwithADHD
WereportacaseofADHDwithnon-mosaicIsodicentricYchromosome.
CASEDESCRIPTION:
A16-year-oldpatientcametothepaediatricOPDwithcomplaintsofhyperactive andrepetitivebehaviour Hewasborntounrelatedparents.Theparentsgavehistoryofnormalbirthwithageappropriatemilestonestill1yearofageafterwhich thechildstartedshowingdelayeddevelopment,lossofspeechandhyperactive behaviour Theygavehistoryofaggressivebehaviouraswell.TherewasnofamilyhistoryofADHD.Theboywasfoundtobephenotypicallynormalafterendocrinologyassessmentbythepaediatrician.Thecouplehasanotheryoungerchild whoisnormal.
TheydidnotconsultanydoctorforADHDandcontinuedtotakehomeopathic medicine.Theysoughtmedicalattentionnowastherepetitivebehaviourwaspersistentandthechildstartedhavingdifficultiesinacademics. Thepaediatricianreferredthepatientforgenetictesting.
MATERIALANDMETHODS:
Informed consent was obtained for Cytogenetic analysis on peripheral blood cells.ChromosomeanalysiswasdoneusingGTGbandingtechniquewitharesolution of 220nm. Two cultures were performed. 56 metaphase chromosomes werecaptured,outofwhich22wereanalysed.12metaphasechromosomeswere karyotyped.
MRI imaging of the brain was done using T1 T2W, FLAIR, SW1 & DW sequencedoneinaxial,sagittalandcoronalplaneusing3.0Teslascanner ThyroidhormoneswereanalysedonautomatedanalyserCobas6000byRoche diagnostics.
DISCUSSION:
TheprevalenceofADHDisfoundtobe7.1%with1.8:1maletofemaleratioin Indianpopulation. Severalgeneshavebeenstudiedtounderstandtheetiology ofADHD but have proved inconclusive. The genetics ofADHD is yet to be unravelledfurther
Presenceofdicentricchromosomeisthemostcommonstructuralaberrationof theYchromosome. MajorityofthepatientswithdicentricYchromosomehavea mosaic karyotype mostly with 45 X cell line. This is because of their mitotic instability and loss during development. Patients with isodicentric chromosomes wary widely in their phenotypic expression from infertility in males to turner'ssyndromeinfemales, gonadaldysgenesis ,shortstature andambiguous genitalia.
IsodicentricYchromosomehavemostlybeenstudiedinazoospermicmales.Sex chromosomesarerelativelyrarelyshowntobeassociatedwithbehaviouraldisorders.
Inthispatient,theThyroidprofilewasnon-significant.TSH2.66uIU/mL(0.224.4uIU/mL),freeT36.04uIU/mL(3.1-6.8uIU/mL)andfreeT410.69uIU/mL (12-22uIU/mL).BrainMRIshowednosignificantabnormality
Cytogenetic analysis identified 46 chromosomes with normal X chromosome andanisodicentricYchromosome(46,X,idic(Y)(q12)(Figure1). Nootherchromosomalabnormalitieswereobserved.Tothebestofourknowledge,onlyone previousstudydiscussesADHDandYchromosomeabnormality Wedidnotdo furthertestingusingFlorescentinsituhybridization(FISH)duetoresourcelimitation.
CONCLUSION:
We report a rare case of non-mosaic isodicentric Y chromosome seen in a phenotypicallynormalmalepatientwithADHD.YchromosomegenesmaycontributetotheriskofADHD.Along-termfollow-upwouldbeneededtoseeifthis chromosomalabnormalitypresentswithfurtherclinicalfeatures.
ClinicalSignificance:Thiscasemaycontributetounderstandingthegeneticsof ADHD.
REFERENCES:
I. Joseph,J.,&devu,B.(2019).Prevalenceofattention-deficithyperactivitydisorderin India:Asystematicreviewandmeta-analysis.IndianJPsyNsg,16,118-25.
II. Faraone,S.,&Larsson,H.(2019).Geneticsofattentiondeficithyperactivitydisorder MolPsychiatry,24(4),562-575.
III. Yoshida,A., Nakahori,Y., Kukori ,Y., Motoyama, M.,Araki,Y., Miura, K., & et al. (1997).DicentricYchromosomeinanazoospermicmale.MolHumReprod,3,709712.
IV Bouayed Abdelmoula, N., & Amouri, A. (2005). Les chromosomes Y dicentriques [DicentricYchromosomes.Firstpart:cytogeneticandmolecularaspects].Annalesde biologieclinique,63(3),263-278.
V Bettio, D., Venci,A., Rizzi, N., Negri, L., & Setti, P (2006). Clinical and molecular cytogeneticstudiesinthreeinfertilepatientswithmosaicrearrangedYchromosomes. Humreprod,21(4),972-5.
VI. Bagci,G.,Acar,H.,&Tomruk,H.(2001).DifferentchromosomeYabnormalitiesin Turnersyndrome.GenetCouns,12(3),255-61.
VII. Kaprova-Pleskacova, J., Snajderova, M., Stoop, J., Koudova, M., Kocarek, E., Novotna, D., & et al. (2013). 45,X/46,X,psu dic(Y) gonadal dysgenesis: influenceof thetwocelllinesontheclinicalphenotype,includinggonadalhistology SexDev,7(6), 282-8.
VIII.Giltay, J., Ausems, M., van Seumeren, I., Zewald, R., Sinke, R., Faas, B., & et al. (2001). Short stature as the only presenting feature in a patient with an isodicentric (Y)(q11.23) and gonadoblastoma. A clinical and molecular cytogenetic study Eur J Pediatr,160(3),154-8.
IX. Pascual, J. M. (2009). Ambiguous genitalia in a newborn with 45,X/46,X,idic(Y) ovotesticulardisorderofsexdevelopment.Endocrpract,15(7),732-736.
X. MulliganA,GillM,FitzgeraldM.(2008).AcaseofADHDandamajorYchromosome abnormality JAttenDisord,12(1):103-105.