1. 1 An Overview of Distal Trisomy 10q Inaugural World Congress On Chromosome Abnormalities June 29, 2004 Daryl Anderson Distal Trisomy 10q Families

2. Addendum  In this presentation, statements are made about most cases are the result of parental translocations. As families have continued to join this community, we are finding that most cases are actually “de novo”. - Daryl, 9/27/2014 April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 2

3. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 3 Overview & Goals  Explore the: what, how, and frequency.  Review its history.  Discuss expression and correlation to 10q segments.  Uncover additional symptoms to watch for.  Relate treatments and therapies.  Propose “next steps”.  Create a more complete database of individuals for future researchers.

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5. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 5 About this Presentation  These slides will be on the web trisomy10q.darylanderson.com  Based on information from 48 papers: PubMed search of Trisomy 10q 48 papers: PubMed search of Trisomy 10q Survey of 12 Distal Trisomy 10q members Survey of 12 Distal Trisomy 10q members

6. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 6 What is Distal Trisomy 10q ?  Distal Trisomy 10q is an extremely rare chromosomal disorder in which the end (distal) portion of the long arm (q) of one chromosome 10 (10q) appears three times (trisomy) rather than twice in cells of the body. - National Org for Rare Diseases (Normally, there are two, and only two, full sets of chromosomes --- this is critical for normal development) (Normally, there are two, and only two, full sets of chromosomes --- this is critical for normal development)

7. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 7 History of the Syndrome  1965: First described de Grouchy and Canet de Grouchy and Canet Chromosome 10 suspected Chromosome 10 suspected  1974: First diagnostic clinical picture Yunis and Sanchez Yunis and Sanchez  1983: Recognized as “Distal 10q” Taysi (et. al.) Taysi (et. al.) Proposed band q25 and q26 as responsible Proposed band q25 and q26 as responsible  1998: First (and only) support group / website Distal Trisomy 10q Families Distal Trisomy 10q Families Originally 6 kids - connected through UseNet postings Originally 6 kids - connected through UseNet postings Grown to 25 kids (plus 2 proximal 10q) Grown to 25 kids (plus 2 proximal 10q)

8. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 8 Trisomy 10q Karyotype (Male)  Karyotype: 23 pairs of chromo’s with X & Y.  One “10” from mom,  One “10” from dad.  In Distal Trisomy 10q, a 3 rd end piece of a “10” from the “q” arm is present.  Now there are 3 “10q” end fragments. University of Washington

9. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 9 Ways 10q Occurs  A few are direct duplication/insertion On end or middle of “10” On end or middle of “10” On another chromo On another chromo  Most are unbalanced translocation Missing part of other chromo Missing part of other chromo Extra piece of 10q Extra piece of 10q University of Washington

10. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 10 Origin of Unbalance Trans-loc’s  First, a balanced translocation occurs in one parent’s karyotype when segments from two different chromo’s accidentally swap…  But the parent has a full and normal set of genes, and therefore is “unaffected” (and likely undetected). University of Washington

11. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 11 Continued…  Next, the child gets a set of chromo’s from one parent with a normal “9” & “10”...  …and from the parent with the balanced transloc… a normal “10” a normal “10” and an abnormal “9” and an abnormal “9”  Now, the offspring has an unbalance transloc yielding partial trisomy 10q and partial monosomy 9q University of Washington

12. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 12 What Research Has Been Done ?  48 papers on 10q since 1965 (tens of thousands on T21, 1000’s on T18) (tens of thousands on T21, 1000’s on T18)  Most papers are case studies Expression in the patient (phenotype) Expression in the patient (phenotype) Methods of detection (cytogenics) Methods of detection (cytogenics)  A few papers propose correlations between phenotype and regions of 10q

13. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 13 How Often Does it Occur ?  Trisomy 21 (Down)1 in 800  Trisomy 18 or 131 in 5,000 ( per synd. )  Distal Trisomy 10q1 in 6,000,000 “pure 10q” 1 in 12,000,000 “pure 10q” 1 in 12,000,000 de novo1 in 32,000,000 de novo1 in 32,000,000 “Pure” includes de novo & xlocs with minimal partial monosomy. “Pure” includes de novo & xlocs with minimal partial monosomy. Frequency in the U.S. population. Survived neonatal. Reporting is highest in U.S. & EU, by far. (World rates, as reported, increases rarity by factor of 5 or 6)

14. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 14 Cumulative Case History PapersCasesSurvived* PapersCasesSurvived* 1965-70:111 1980:162419 1990:263725 2000:385233 2003:485839 * lived past neonatal

15. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 15 Where Are They  Published Reports 39  Chromosome Deletion Outreach 4  Distal Trisomy 10q Families25 Total (after duplications removed) ~ 62 Note: There are certainly more, but these are the ones known in the research and to the single Trisomy 10q support organization.

16. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 16 Stupid Math Trick Averaging one “de novo” born every 8 years in the U.S., what is the probability of two de novo’s being born on the same day ? Answer: 100% (a priori)

17. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 17 Please Meet  Born: Oct 1, 1993  10q25.3  qter de novo  Corvallis, Oregon  Jess Anderson  Born: Oct 1, 1993  10q25.3  qter de novo  Redford, Michigan  Josh Smith

18. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 18 Jess & Josh Meet --- 2002 Henry Ford Museum

19. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 19 Stupid Math Trick Revisited Answer:1 in 2,850 (in a given year) Answer:1 in 2,850 (in a given year) 1 in (1/8 de novo per year / 365)^2 * 365 1 in (1/8 de novo per year / 365)^2 * 365

20. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 20 Expression of the Syndrome (symptoms that “may” occur)  Dysmorphic craniofacial features  Mental retardation (greatly varying)  Growth retardation  Psychomotor retardation (fine motor, speech)  Hypotonia (weak muscles)  Heart & Kidney Defects  Kyphoscoliosis (humped back / scoliosis)  Camptodactyly (flexed / crossed fingers)  Wide gap between 1 st & 2 nd toes

21. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 21 Features of the Syndrome  Narrow eye openings  Up-slanting eyes  Arched eyebrows  Arched palate (cleft)  Flat nose bridge  Bow shaped mouth  Small, low set ears  Short neck  Sloping shoulders

22. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 22 A Few Smiles IvyEmilyBryan

23. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 23 Chromosome 10 Ideogram From NCBI.NIH.COM Website

24. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 24 Segments vs. Phenotype (approximate*)  10q26 Facial Dysmorphism, mental and growth retardation Facial Dysmorphism, mental and growth retardation  10q25 Mild vision, hearing, and speech issues Mild vision, hearing, and speech issues  10q24 Heart and Kidney issues Heart and Kidney issues Ocular issues Ocular issues  10q23  10q22 Severe ocular issues Severe ocular issues Dysmorphism of limbs Dysmorphism of limbs * Based on small set of data. Cases with little or no associated partial monosomy. * Based on small set of data. Cases with little or no associated partial monosomy.

25. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 25 Notes on Following Charts  The following two charts attempt to show the correlation of various 10q segment lengths to heart and kidney issues.  Each bar represents the additional 10q segment of a specific child.  The terminals of each bar map to the segment start and end points (x-axis).  Green bars indicate heart / kidney issues.

26. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 26

27. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 27

28. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 28 Segments vs. Phenotype Major exception: Translocation onto chromosome X can “inactivate” significant segments of 10q, resulting in no, or milder symptoms. Examples: q23.3  qter No features of 10q q23.3  qter No features of 10q q21  qter Moderate mental retardation and significant dysmorphism. q21  qter Moderate mental retardation and significant dysmorphism. q11.2  qter Only some minor 10q facial dysmorphism and speech delay. q11.2  qter Only some minor 10q facial dysmorphism and speech delay.

29. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 29 Treatments and Watch List Soon After Birth  Evaluate heart ASD,VSD,PDA,sub-aortic membrane, ejection murmur, hypertrophic cardiomyopathy, ASD,VSD,PDA,sub-aortic membrane, ejection murmur, hypertrophic cardiomyopathy,  Evaluate kidneys (etc.) Hydronephrosis, dysmorphic, hydroureters Hydronephrosis, dysmorphic, hydroureters  Check and watch lungs (pneumonia)  Functioning of intestines, malrotations (movement of food)

30. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 30 Treatments and Watch List Later  Speech therapy: Start as early as possible.  Test hearing. FM wireless for school. Ear tubes.  Watch for strabismus (lazy eye). Catch early.  Occupational and physical therapy.  Watch for bladder control issues.  Consider a palate spreader – 4-5 yrs age? Room for teeth -- helps with speech Room for teeth -- helps with speech  Allergies  Basilar invagination ?

31. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 31 What is Needed?  Treatments are needed to counteract the symptoms of this syndrome.  From the surveys of 10q parents, the common theme was a desire for better and more up to date information on 10q symptoms and treatments.  Also mentioned was that doctors should try to link up new families to others with 10q.

32. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 32 Appreciation  Families that participated in the survey  Congress organizers  HP-IPG Research Library Corvallis, OR  Kory Keller of OHSU -- Consulting  Chromosome Deletion Outreach

33. April 8, 2004 Distal Trisomy 10q Families World Congress on Chromosome Ab. 33 Distal Trisomy 10q Families trisomy10q @ darylanderson. com trisomy10q. darylanderson. com