Research Update Spring 2011

Transcription

1 Research Update Sprng 2011 Research Update Sprng 2011 EMORY DOWN SYNDROME RESEARCH 2011 Who we are The people behnd the research Stephane Sherman, PhD Emory Down Syndrome Project Drector Lora Bean, PhD Down Syndrome and Congental Heart Defects Project Drector Jeanne Vsootsak, MD Down Syndrome Clnc Medcal Drector Heather Clark, MS, CGC Down Syndrome Clnc Coordnator Adrenne Perkns, M.Ed, MS Down Syndrome Clnc Educatonal Consultant Helen Smth, RN, MSN Nurse Researcher Elzabeth Sablón, BSW Project Coordnator Trace Rosser, PhD Project Coordnator How to reach us Emory Down Syndrome Project Attn: Helen Smth Department of Human Genetcs 1462 Clfton Road, Sute 300 Mal stop AB Atlanta, GA Phone: Fax: Emal: En Espanola, Teléfono: Natonal Down Syndrome Regstry and Bobank: Resources to advance understandng and treatment of Down syndrome Two recent meetngs brought together the Down syndrome communty and partners to dscuss the need for new resources to help move clncal research ahead quckly and effcently. These meetngs ncluded the Down Syndrome Regstry Meetng n September 2010 sponsored by the Natonal Down Syndrome Socety, and the Down Syndrome: Natonal Conference on Patent Regstres, Research Databases, and Bobanks n December 2010 sponsored by the Eunce Kennedy Shrver Natonal Insttute of Chld Health and Human Development (NICHD) and the Global Down Syndrome Foundaton. These meetngs focused on the need to buld new research tools, ncludng a contact regstry, a clncal research database, and a bobank. All are resources that wll help maxmze the efforts of the famles who take part n research as well as ncrease collaboratons among scentsts, health professonals, and educators. The purpose of a Down Syndrome Contact Regstry s to allow ndvduals wth Down syndrome and ther famles to regster themselves nto a database so they can be contacted about clncal research opportuntes. Ths contact regstry would nclude the regstrant s contact nformaton and a short descrpton of ther famly member wth Down syndrome. The contact regstry would help researchers dentfy and recrut ndvduals who are elgble and mght be nterested to partcpate n ther clncal research study. Ths contact regstry would also be used to send out nformaton about the progress and fndngs from each research project. Many tmes these types of regstres are created and mantaned by the advocacy communty. A structure to govern access to regstrants s mportant. All proposed clncal research projects would be revewed by experts n the feld to determne ther potental sgnfcance to the Down syndrome communty. Regstrants would be contacted only after a project s approved. Insde ths ssue: Down Syndrome Regstry 1-2 Emory Down Syndrome Studes Update 3 The Congental Heart Defects Update 4 The 3-D FACES Study 5 Down Syndrome Cognton Study Update 6-7 Our Latest Publcatons 8-9 The Down Syndrome Clnc at Emory Our Msson Statement 12

2 Down Syndrome Regstry cont. The purpose of a Down Syndrome Clncal Research Database s dfferent. Clncal research databases collect, store, catalog, and share nformaton to qualfed scentsts. They are usually drven by specfc research projects that have ther own ams. The collected de-dentfed data (that s, data that does not nclude names or personal dentfers) can be shared f every project uses standardzed collecton methods and terms. These clncal databases would provde nformaton about the natural hstory of Down syndrome throughout an ndvdual s lfespan. Ths nformaton would help to better understand lfe transtons and the clncal and medcal factors that affect qualty of lfe, medcal condtons, and survval. Rght now, the data we have are manly stored n the databases of ndvdual clncans and nvestgators. There s no centralzed or consoldated clncal research database at ths pont. The computer technology s smple. The standardzaton and the resources to push the data nto one place are more complcated. But t can be done! The purpose of a Down Syndrome Bobank s to collect, catalog, store and dstrbute specfc tssues and fluds to approved scentsts wthn the basc and clncal research communtes. There are exstng bobanks that are specfc to a dsorder or to a type of tssue (for example, a bran tssue bobank.) There are bobanks that are more general and take any type of tssue from ndvduals wth any dsorder. Agan, no names or personal dentfers are stored wth the sample. Only a mnmum amount of clncal data s stored to help understand the source of the tssue. Bobanks are created by prvate groups (usually non-proft) or by the advocacy communtes. We learned from these meetngs that there s a lot of experence n buldng these resources for other dsorders. We do not have to start from scratch. Nonetheless, t wll take a large effort from everyone to develop these mportant resources. Emory and our research partners are commtted to buldng these tools. Representatves from each of our collaboratve nsttutons have attended these meetngs and played a large role n the dscussons. Our research database s one of the largest n the world. Wth proper consent, we wll share de-dentfed nformaton through a centralzed database wth other researchers nvolved n Down syndrome studes. We also have a large repostory of DNA from ndvduals wth Down syndrome and ther famles. Agan wth proper consent, we wll send samples to the bobank for dstrbuton. Wth new scentfc and technologcal advances, scentsts are ready to make novel and clncally relevant research dscoveres. We thnk these dscoveres wll come faster wth these centralzed resources. In addton to our own work toward ths goal, NICHD put out a Request for Informaton (RFI) to get nput from the wder communty. One s for the Down syndrome clncal database and regstry (NOT-HD-11_002)(f the lnk doesn t work, copy the followng nto the URL bar: and another for the Down syndrome bobank (NOT-HD ) ( html). You can go on-lne to see ths process. Many of you responded wth suggestons and support. Everyone's nput s hghly valued. Emory s plannng to work wth a natonal bobank to allow other researchers to access bologcal samples from our current study partcpants f they consent to be ncluded n the bobank. Please look for a new consent form n the mal soon and contact us f you have any questons about the bobankng opportunty. RESEARCH UPDATE SPRING 2011 Page 2

3 Emory Down Syndrome Study Update EDSP and CHD The Emory Down Syndrome Project began n 2005 and s currently trackng over 540 famles, wth approxmately 340 complete cases. The purpose of the study s to combne nformaton from ntervew questons wth laboratory data on the behavor of chromosomes to further understand what causes Down syndrome and ts related medcal problems. More specfcally, why do some chldren wth Down syndrome have more medcal problems such as heart defects and gastrontestnal defects than others? Another component of the Emory Down Syndrome Project was the Famly Study whch ncluded sblngs and grandparents of chldren wth Down syndrome. We fnshed recrutment for the Famly Study n 2010 wth over 250 famles partcpatng. By studyng many three-generaton famles, we wll be able to learn more about how chromosomes behave and explore the mportance of specfc genes on chromosome 21. The bologcal samples have been sent for genotypng, and the data are beng analyzed. Thank you to all the extended famly members who made ths project possble! We are also recrutng chldren wth Down syndrome to partcpate n an NIH-funded study to dentfy genetc and envronmental factors related to congental heart dsease (CHD) n Down syndrome. The goal s to understand why some chldren wth Down syndrome have heart defects and others do not. Ths study s a collaboratve effort between stes at the Kennedy Kreger Insttute and Johns Hopkns Unversty, both n Baltmore, MD, Emory Unversty n Atlanta, GA, Oregon Health & Scence Unversty n Portland, OR, and Chldren s Natonal Medcal Center n Washngton, D.C. You can read more about ther updates on the followng pages. Fndngs from ths project wll help us to understand congental heart defects n all chldren. We have enrolled almost 900 famles across stes snce Our prevous work has focused on heart development n ndvduals wth Down syndrome. We have recently started to explore another area of heart research, one related to cardovascular functon. Dr. Clff Cua s a pedatrc cardologst at Natonwde Chldren s Hosptal n Columbus, Oho, who has worked wth the Emory Down Syndrome Project for several years. Hs nterest n Down syndrome and research has enabled famles, whose chld wth Down syndrome s treated at Natonwde Chldren s Hosptal, to learn about and enroll n our studes here at Emory. Dr. Cua s nterested n a partcular problem wth cardovascular functon pulmonary hypertenson. Pulmonary hypertenson s hgh blood pressure n the lungs. Dr. Cua conducted a study n 2007 n whch he found that nfants wth Down syndrome were more lkely than expected to have pulmonary hypertenson. Snce many nfants wth Down syndrome have complex medcal problems, n partcular heart defects, understandng the rsk for pulmonary hypertenson n the group s mportant. Workng wth Dr. Clff Cua and wth Dr. Ken Dooley at the Sbley Heart Center, Chldren s Healthcare of Atlanta, we wll look for evdence of pulmonary hypertenson n nfants partcpatng n the Down syndrome studes here at Emory to try to dentfy rsk factors for ths condton. RESEARCH UPDATE SPRING 2011 Page 3

4 Congental Heart Study Update Johns Hopkns Unversty/Kennedy Kreger Insttute/ Chldren s Natonal Medcal Center Update At the Johns Hopkns/Kennedy Kreger Insttute stes, we are combnng our study recrutng efforts nto a sngle, cohesve project: the Down Syndrome Phenotype Project. Our goal s to reduce the tme and effort requred for famles to partcpate n all aspects of our research, ncludng the DS Heart Project, the DS Cognton Study, and DS Faces. Combnng nformaton from multple systems (heart, bran, face, GI tract) gves us a better understandng of the mechansms that underle the characterstcs of Down syndrome. We re currently at work settng up socal networkng stes to make t easer for us to share progress and mlestones n the research wth the famles who made t all possble. In the next ssue of the newsletter, look for nformaton about our new Facebook and Twtter stes!! We re also plannng to be at the Internatonal Mosac Down Syndrome Assocaton (IMDSA) 5 th Bennal Research & Awareness Conference at Walt Dsney World n Orlando, Florda, (July 8-10, 2011). We ll have a space reserved, and we re specfcally lookng for famles wth mosac Down syndrome for a unque study on the functon of dfferent types of cardac cells. If you re attendng the meetng (or just vstng Dsney World) stop by and say hello! Enrollment for the DS Heart Project at the combned Johns Hopkns/Kennedy Kreger Insttute/ Chldren s Natonal Medcal Center stes has reached a total of 232 famles! Thank you to all the famles who have been a part of ths mportant work! Oregon Health & Scence Unversty Update Oregon Health & Scence Unversty currently serves as one of fve stes for the natonwde Down Syndrome Heart Project. Lead by prncpal nvestgator, Cheryl Maslen, Ph.D, we have enrolled over 100 study partcpants and ther famles. Most of our recrutment has been conducted through the Down Syndrome Clnc at Doernbecher Chldren s Hosptal wth the help of Joseph Pnter, M.D. Dr. Pnter serves as the Medcal Advsor for the Down Syndrome Informaton Allance, and hs research has focused on neuromagng n congental bran anomales and Down syndrome. We are also currently enrollng chldren to partcpate n the natonal Down Syndrome Cognton Study. Partcpants n the cognton study are admnstered a seres of computer tests whch wll provde clncans wth a new way to assess the cogntve abltes of people wth Down syndrome. Thanks to all our partcpants for makng ths research possble! If you would lke to learn more about the Down syndrome research studes at Oregon Health & Scence Unversty, please contact our patent recrutment coordnator, Katy Lesowsk at or lesowsk@ohsu.edu. We wll have a booth at the upcomng Natonal Down Syndrome Conference n San Antono the weekend of August 5 th through the 7 th, Please stop by to say h and learn more about our research! Page 4 RESEARCH UPDATE SPRING 2011

5 Emory Jons Penn State n 3-D FACE Study Emory has joned Pennsylvana State Unversty n a study of phenotypc varaton n Down syndrome. Joan Rchtsmeer, PhD, and graduate student, John Starbuck of Penn State, contnue to collect 3D mages of the faces of ndvduals wth Down syndrome and ther sblngs to explore facal varaton caused by trsomy 21. The 3-D mages of ther typcal sblngs are beng collected as the comparson group. Trace Rosser, Helen Smth, and Elzabeth Sablon of Emory plan to start enrollng partcpants n Atlanta later ths year. These researchers want to understand how trsomy 21 affects facal development and alters patterns of facal varaton wthn and between dfferent regons of the face (e.g. upper, mddle, and lower facal regons.) Prelmnary analyss shows that patterns of facal varaton are smlar for many regons of the face; however, there are dfferences for the measure of dstances n the lower regon of the face and between the mddle and lower regons of the face. Ths suggests that the extra chromosome 21 affects the facal promnences that form, grow, move, and come together to produce the face. Ths study wll begn to help understand facal varaton due to trsomy 21 that may lead to problems such as sleep apnea. Approxmately 500 ndvduals have been enrolled nto ths study and approxmately 500 more are needed. Data collecton wll contnue throughout most of To partcpate, a trp to the Image Analyss and Morphometrcs Laboratory at Penn State s Unversty Park campus or to Emory s Down Syndrome Clnc s requred. It typcally takes 5-10 mnutes per famly to collect 3D facal mages and complete consent forms. The researchers are wllng to consder travelng to locatons where groups of ndvduals may be nterested n partcpatng n ths study; however, ths wll depend on how far away the locaton s and how many people wll be enrolled nto the study at that locaton. For more nformaton, please contact Joan jta10@psu.edu or John jms1043@psu.edu at Penn State or Trace at Emory trosser@emory.edu. Gong Green We are plannng to send future newsletters by emal and have them avalable on our webste n Englsh and n Spansh. Please contact us f we do not have your current emal so that we can stay connected. Thanks!! Trace Rosser or trosser@emory.edu. Stop n to say H! Internatonal Mosac Down Syndrome Assocaton (IMDSA) 5 th Bennal Research & Awareness Conference at Walt Dsney World, Florda (July 8-10, 2011). Natonal Down Syndrome Conference n San Antono (August 5-7, 2011). Page 5 RESEARCH UPDATE SPRING 2011

6 Down Syndrome Cognton Study Update Emory Emory Unversty s part of a natonwde study to understand the dfferences and smlartes n learnng abltes among ndvduals wth Down syndrome. Ths s a contnuaton and expanson of the plot study started n Its purpose s to understand more about how chldren wth Down syndrome learn and problem solve. We are also gatherng nformaton about certan medcal condtons related to Down syndrome to determne how they may affect learnng abltes. Fnally, we plan to collect DNA samples to dentfy genes that play a role n these learnng pathways. The other stes partcpatng n the study nclude: Johns Hopkns Unversty and Kennedy Kreger Insttute n Baltmore, MD; Unversty of Arzona n Tucson, AZ; Oregon Heath & Scence Unversty n Portland, OR, and The Wasman Center at the Unversty of Wsconsn Madson, WI. We hope to expand to Chldren s Natonal Medcal Center n Washngton, D.C. later ths year. Ths large scale, mult-ste project wll have the power to dentfy factors, both genetc and envronmental, that lead to the varaton n cogntve functonng seen n ndvduals wth Down syndrome. If we can understand the systems nvolved n cognton and the factors that play a crtcal role, we wll have a hgher chance of developng evdence-based nterventon programs. The fundng for ths project has been provded by the Down Syndrome Research and Treatment Foundaton. We are grateful for ther support. Partcpants come to Emory or one of the other stes for one testng sesson that may last up to two hours each. Your chld wll be asked to complete cogntve tests. Most tests wll be done on a computer and are just lke a computer game. Other tests wll be gven by a traned researcher. In these tests your chld wll be asked to sort cards, pont to pctures or draw. We wll also ask you to complete three short wrtten questonnares regardng the everyday sklls and behavor of your chld. We wll also need a small blood sample from your chld whch can be arranged durng a routne medcally necessary blood draw. We wll also need to collect a small salva sample from both parents f avalable. We wll ask you to sgn a form that wll gve us permsson to obtan medcal records on your chld, to fnd out f he or she has any of the medcal problems often seen n chldren wth Down syndrome. If you are nterested n consderng enrollng your chld n ths study or have questons about the project, please contact: Trace Rosser Phone: Emal: trosser@emory.edu RESEARCH UPDATE SPRING 2011 Page 6

7 Down Syndrome Cognton Study Update Arzona 2010 was a wonderful year for Down syndrome research! We are proud to be a part of t. Some of the hghlghts of our projects are lsted below, but frst we want to thank our partcpants for all ther efforts. Cogntve Assessment-Our cogntve test battery, the Arzona Cogntve Test Battery for Down Syndrome, was publshed n the Journal of Neurodevelopmental Dsorders (Edgn et al., 2010), and hghlghted across the web and on NPR arzona/archves/201009/down_testng.we have receved fundng from the Foundaton Jerome Lejeune n Pars to examne the use of our tests n agng adults, and new tests are beng desgned for use wth younger chldren. The Effects of Second Language Learnng -In a study just accepted for publcaton n the Journal of Intellectual Dsabltes Research (Edgn et al., n press), t was shown that moderate exposure to a second language s not detrmental to cogntve development n chldren wth DS. Sleep Apnea Effects -We have just been funded by the Thrasher Medcal Research Foundaton for three years to complete sleep studes and determne effects of sleep apnea n Down syndrome! We are stll recrutng for sleep studes n Arzona. Many famles have gotten useful feedback post-adenod and tonsllectomy surgery or nformaton regardng the presence of apnea. Understandng Varablty n Outcome-We are a ste of the Down Syndrome Phenotype Project (DSPP), recrutng ndvduals years for assessments of cogntve functon, health and genetc correlatons of these outcomes. Work on Down syndrome s on the move! In November we presented four posters at the Socety for Neuroscence meetng n San Dego, CA. Over 60 abstracts focusng on DS were presented, wth the frst-ever symposum wth Down syndrome as the sole topc. A round table event sponsored by the Down Syndrome Research and Treatment Foundaton also brought researchers together to dscuss the next steps. We have research opportuntes for ndvduals wth Down syndrome from age seven through adulthood n Arzona. We can sometmes travel to the western states. Call or emal jedgn@emal.arzona.edu. Page 7 RESEARCH UPDATE SPRING 2011

8 Our Latest Publcatons See complete artcle n: Human Genetcs 2009 Feb;125(1): Maternal age and rsk for trsomy 21 assessed by the orgn of chromosome nondsjuncton: a report from the Atlanta and Natonal Down Syndrome Projects. Allen EG, Freeman SB, Druschel C, Hobbs CA, O'Leary LA, Romtt PA, Royle MH, Torfs CP, Sherman SL. Abstract: We examned the assocaton between maternal age and chromosome 21 nondsjuncton by orgn of the meotc error. We analyzed data from two populatonbased, case-control studes: Atlanta Down Syndrome Project ( ) and Natonal Down Syndrome Project ( ). Cases were lve born nfants wth trsomy 21 and controls were nfants wthout trsomy 21 delvered n the same geographcal regons. We enrolled 1,215 of 1,881 elgble case famles and 1,375 of 2,293 controls. We report four prmary fndngs. Frst, the sgnfcant assocaton between advanced maternal age and chromosome 21 nondsjuncton was restrcted to meotc errors n the egg; the assocaton was not observed n sperm or n post-zygotc mtotc errors. Second, advanced maternal age was sgnfcantly assocated wth both meoss I (MI) and meoss II (MII). For example, compared to mothers of controls, mothers of nfants wth trsomy 21 due to MI nondsjuncton were 8.5 tmes more lkely to be >or=40 years old than years old at the brth of the ndex case (95% CI= ). Where nondsjuncton occurred n MII, mothers were 15.1 tmes more lkely to be >or=40 years (95% CI = ). Thrd, the rato of MI to MII errors dffered by maternal age. The rato was lower among women <19 years of age and those >or=40 years (2.1, 2.3, respectvely) and hgher n the mddle age group (3.6). Lastly, we found no effect of grand-maternal age on the rsk for maternal nondsjuncton. Ths study emphaszes the complex assocaton between advanced maternal age and nondsjuncton of chromosome 21 durng oogeness. See complete artcle n: Amercan Journal of Medcal Genetcs A Aug;149A(8): Investgaton of factors assocated wth paternal nondsjuncton of chromosome 21. Olver TR, Bhse A, Fengold E, Tnker S, Masse N, Sherman SL. Abstract: Prevous studes on relatvely small samples of ndvduals wth trsomy 21 caused by paternally derved errors have shown that: (1) advanced paternal age s not a rsk factor for chromosome 21 nondsjuncton (NDJ), (2) absence of recombnaton, but not the locaton of recombnaton s assocated wth paternal NDJ, and (3) there s an excess of males among lve-brths wth paternally derved trsomy 21. An excess of males s also observed among all ndvduals wth trsomy 21. Usng 128 famles that had a chld wth trsomy 21 due to a paternally derved error, we examned: paternal age, recombnaton and the male/female sex rato. We genotyped STRs along 21q to dentfy the orgn of the error and the locaton of recombnaton on the paternal chromosome. Results showed that 32% of paternal meotc errors occurred n meoss I (MI) and 68% n meoss II (MII). We confrmed the lack of a paternal age assocaton wth ether type of error (mean paternal age for controls, MI, and MII errors: /- 6.6, /- 6.3, /- 6.5, respectvely). However, contrary to prevous fndngs, we dd not fnd altered patterns of recombnaton among paternal MI or MII errors. We found an ncreased male/female sex rato among paternal (1.28, 95% CI: ) and maternal (1.16, 95% CI: ) meotc errors. Whle the sex rato among ndvduals wth paternal errors was not statstcally sgnfcant, these fndngs suggest that selecton aganst female fetuses wth trsomy 21 may contrbute to the excess of males observed among all ndvduals wth trsomy 21. Page 8 RESEARCH UPDATE SPRING 2011

9 Our Latest Publcatons See complete artcle n: Journal of Neurodevelopmental Dsorders Sep 1;2(3): Development and valdaton of the Arzona Cogntve Test Battery for Down syndrome. Edgn JO, Mason GM, Allman MJ, Capone GT, Deleon I, Maslen C, Reeves RH, Sherman SL, Nadel L. Abstract: Neurocogntve assessment n ndvduals wth ntellectual dsabltes requres a well-valdated test battery. To meet ths need, the Arzona Cogntve Test Battery (ACTB) has been developed specfcally to assess the cogntve phenotype n Down syndrome (DS). The ACTB ncludes neuropsychologcal assessments chosen to 1) assess a range of sklls, 2) be non-verbal so as to not confound the neuropsychologcal assessment wth language demands, 3) have dstrbutonal propertes approprate for research studes to dentfy genetc modfers of varaton, 4) show senstvty to wthn and between sample dfferences, 5) have specfc correlates wth bran functon, and 6) be applcable to a wde age range and across contexts. The ACTB ncludes tests of general cogntve ablty and prefrontal, hppocampal and cerebellar functon. These tasks were drawn from the Cambrdge Neuropsychologcal Testng Automated Battery (CANTAB) and other establshed paradgms. Alongsde the cogntve testng battery we admnstered benchmark and parent-report assessments of cognton and behavor. Indvduals wth DS (n=74, ages 7-38 years) and mental age (MA) matched controls (n=50, ages 3-8 years) were tested across 3 stes. A subsample of these groups were used for between-group comparsons, ncludng 55 ndvduals wth DS and 36 mental age matched controls. The ACTB allows for low floor performance levels and partcpant loss. Floor effects were greater n younger chldren. Indvduals wth DS were mpared on a number of ACTB tests n comparson to a MA-matched sample, wth some areas of spared ablty, partcularly on tests requrng extensve motor coordnaton. Battery measures correlated wth parent report of behavor and development. The ACTB provded consstent results across contexts, ncludng home vs. lab vsts, crossste, and among ndvduals wth a wde range of soco-economc backgrounds and dfferences n ethncty. The ACTB wll be useful n a range of outcome studes, ncludng clncal trals and the dentfcaton of mportant genetc components of cogntve dsablty. See complete artcle n: Genetc Epdemology Sep;34(6): Varaton n folate pathway genes contrbutes to rsk of congental heart defects among ndvduals wth Down syndrome. Locke AE, Dooley KJ, Tnker SW, Cheong SY, Fengold E, Allen EG, Freeman SB, Torfs CP, Cua CL, Epsten MP, Wu MC, Ln X, Capone G, Sherman SL, Bean LJ. Abstract: Cardac abnormaltes are one of the most common congental defects observed n ndvduals wth Down syndrome. Consderable research has mplcated both folate defcency and genetc varaton n folate pathway genes wth brth defects, ncludng both congental heart defects (CHD) and Down syndrome (DS). Here, we test varaton n folate pathway genes for a role n the major DS-assocated CHD atroventrcular septal defect (AVSD). In a group of 121 case famles (mother, father, and proband wth DS and AVSD) and 122 control famles (mother, father, and proband wth DS and no CHD), tag SNPs were genotyped n and around fve folate pathway genes: 5,10-methylenetetrahyrdofolate reductase (MTHFR), methonne synthase (MTR), methonne synthase reductase (MTRR), cystathonne beta-synthase (CBS), and the reduced folate carrer (SLC19A1, RFC1). SLC19A1 was found to be assocated wth AVSD usng a multlocus allele-sharng test. Indvdual SNP tests also showed nomnally sgnfcant assocatons wth odds ratos of between 1.34 and 3.78, dependng on the SNP and genetc model. Interestngly, all margnally sgnfcant SNPs n SLC19A1 are n strong lnkage dsequlbrum (r(2)> or = 0.8) wth the nonsynonymous codng SNP rs (c.80a>g), whch has prevously been assocated wth nonsyndromc cases of CHD. In addton to SLC19A1, the known functonal polymorphsm MTHFR c.1298a was over-transmtted to cases wth AVSD (P=0.05) and under-transmtted to controls (P=0.02). We conclude, therefore, that dsrupton of the folate pathway contrbutes to the ncdence of AVSD among ndvduals wth DS. Page 9 RESEARCH UPDATE SPRING 2011

10 The Down Syndrome Clnc at Emory Unversty The Emory Down Syndrome Center, establshed n 2003, ncludes educaton, research, and an mportant clncal component, the Down Syndrome Clnc. The prmary goal of the clnc s to meet the needs of ndvduals wth Down syndrome and ther famles. For those of you who are not famlar wth our servces, we d lke to gve you an ntroducton and answer some of your questons. What s the age lmt? Whle our long-range goal s to see ndvduals of any age who have Down syndrome, we currently have the followng lmts: New patents. Brth to age eght years Returnng patents. We have rased our age lmt so that chldren who we frst saw before age three years can contnue to return to clnc after ther thrd brthday. How do I make a clnc appontment? To make an appontment, please contact Heather Clark at or hmclark@emory.edu. Spanshspeakng famles can call Elzabeth Sablon, our medcal nterpreter, at We thnk t s mportant that parents are the ones to make the appontment. The ntal phone call gves us the opportunty to explan the clnc and determne f there s nformaton about Down syndrome that the famly needs mmedately. If so, we can often provde t by phone or mal pror to ther clnc appontment. How s a vst to the Down Syndrome Clnc dfferent from a vst to a pedatrcan? We are not a substtute for a pedatrcan. As wth any chld, your goal should be to select a pedatrcan whom you trust to provde all the best general pedatrc care and wll be avalable for those mdnght earaches! Our clnc combnes genetcs and developmental pedatrcs. What does a clnc vst nclude? A revew of your chld s medcal hstory. When parents schedule an appontment, we ask for permsson to get ther chld s medcal records. Informaton from the brth hosptal, pedatrcan, and any specalsts helps us get to know your chld. For example, we can make sure that all recommended tests such as a hearng screen, thyrod test, and cardac evaluaton have been completed adequately. A dscusson of your chld s chromosome report. Parents often want to know more about how Down syndrome occurs, what an extra chromosome 21 means for ther chld, and f there s an ncreased chance for another chld wth Down syndrome n the famly. A physcal exam. We complete a basc physcal exam of your chld and make a specal effort to answer any questons you have about features characterstc of Down syndrome. A developmental evaluaton. Our medcal drector, Dr. Jeanne Vsootsak, s a board-certfed developmental pedatrcan. After conductng a developmental evaluaton, she dscusses her fndngs wth parents. Recommendatons are made for the tmng and frequency of early nterventonal therapy (physcal, occupaton, speech/language.) Each chld s an ndvdual wth developmental strengths and challenges. Our goal s to dentfy these strengths and challenges and make recommendatons to maxmze each chld s potental. An explanaton of the Healthcare Gudelnes for Chldren wth Down Syndrome. These natonal gudelnes provde parents and physcans wth a concse outlne of specal tems of care and ther tmng (e.g., cardac evaluaton, vson and hearng exams, thyrod tests.) Referrals. Based on each chld s medcal hstory, physcal examnaton, and developmental evaluaton, approprate specalsts and/or therapsts are suggested f needed. Answer questons. Ths s perhaps the most mportant part of your vst. We urge parents to come wth ther questons. Each famly who vsts our clnc s n a dfferent place n terms of ther knowledge of Down syndrome and ther understandng of what the dagnoss means for ther chld. We try to talor vsts to each famly s needs. Where s the Down Syndrome Clnc located? The clnc s located n our new faclty just off the Emory campus near the corner of North Decatur and Clarmont Roads. The address s 2165 North Decatur Rd., Decatur, GA and parkng s easy! How do I fnd out more about the clnc? Heather Clark, Clnc Coordnator, wll be glad to answer questons related to the clnc, , hmclark@emory.edu). All of us n the Down Syndrome Clnc thank the Down Syndrome Assocaton of Atlanta for ts contnung support. We couldn t do t wthout them! Jeanne Vsootsak, MD Heather Clark MS, CGC Adrenne Perkns, M.Ed, MS Helen Smth, BSN Elzabeth Sablon, BSW Page 10 RESEARCH UPDATE SPRING 2011

11 Welcome Heather and Adrenne to the Down Syndrome Clnc The Emory Down Syndrome Clnc s excted to ntroduce two new members of our clnc team. Heather Clark, MS, CGC, s a board-certfed genetc counselor and has worked n the Emory Unversty Department of Human Genetcs for the past seven years. Heather obtaned her Bachelor of Arts degrees from Augustana College n Rock Island, Illnos, where she studed bology, pre-medcne, and socology. She obtaned her Master of Scence degree n Medcal Genetcs from the Unversty of Cncnnat n Oho. Heather s prevous clncal work focused on prenatal and reproductve genetcs, pedatrc genetcs, and a group of specalty genetc dsorders called lysosomal storage dseases. She s also an experenced study coordnator for numerous clncal trals nvestgatng new treatment medcatons for lysosomal storage dseases. Heather s responsble for schedulng famles for clnc. As you may know, we ask that famles call drectly to make ther chld s appontment. Ths gves us an opportunty to get acquanted and explan what s nvolved n a typcal clnc vst. The clnc currently serves chldren wth Down syndrome from brth through age eght years. For more nformaton about the Emory Down Syndrome Clnc or to schedule an appontment, please contact Heather Clark at or hmclark@emory.edu. Adrenne Perkns, M.Ed, MS, s a certfed school psychologst and doctoral student n Georga State Unversty s doctoral program n School Psychology. She obtaned her Bachelor of Scence degree n Bology from Bennett College n Greensboro, North Carolna, and her Master of Scence degree from the Unversty of Dayton n Oho. Adrenne also earned a Master of Educaton degree n School Psychology at Georga State Unversty where she wll obtan her Educaton Specalst degree n December. Adrenne has eght years of professonal experence as a secondary scence teacher. She also has two years of experence conductng psychoeducatonal evaluatons for local school dstrcts. Adrenne s responsble for performng psychologcal assessments related to current Down syndrome research projects. She also serves as an educatonal consultant for famles of chldren wth Down syndrome by dentfyng educatonal resources and revewng Indvdualzed Educaton Plans. WELCOME To the Down Syndrome Clnc! Heather Clark, MS, CGC Adrenne Perkns, M.Ed., MS RESEARCH UPDATE SPRING 2011 Page 11

12 S desea una copa en español, por favor llame a la Sra. Elzabeth Sablón al EMORY DOWN SYNDROME PROJECT Emory Unversty, Department of Genetcs 1462 Clfton Road Mal stop AB Atlanta, GA Phone: Fax: Emal: edsp@genetcs.emory.edu En Espanola, Teléfono: Return Servce Requested Our Msson Statement Trsomy 21, the leadng cause of Down syndrome, occurs when a chld receves three copes of chromosome 21 nstead of the usual two copes. Ths s almost always due to a chromosome error durng the formaton of ether the egg or the sperm (see fgure at rght). Our frst goal s to dscover how these errors occur and dentfy factors that affect ths process. Secondly, we want to understand why an extra chromosome 21 causes Down syndrome. We hope to dentfy specfc genes on chromosome 21 that alter development and produce the ntellectual dsablty, congental heart defects, and other health problems assocated wth Down syndrome. Our hope s that ncreasng knowledge about Down syndrome wll beneft famles, educators, and health professonals. Both father and mother have 46chromosomes or 23 pars, ncludng 2 copes of chromosome 21. Here we show only the par of chromosome 21. Occasonally, an egg or sperm s formed wth an extra copy of chromosome 21. The father s sperm have 1 copy of each par of chromosomes, ncludng chromosome 21. The mother s eggs have 1 copy of each par of chromosomes, ncludng chromosome 21. Ths example shows the extra chromosome formng n the egg. Unon of ths egg wth a normal sperm leads to a chld wth 3 copes of chromosome 21 - trsomy 21 Down syndrome.