An Overview of Distal Trisomy 10q

1. An Overview ofDistal 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 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. Distal Trisomy 10q Families World Congress on Chromosome Ab.

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5. About this Presentation • These slides will be on the webtrisomy10q.darylanderson.com • Based on information from • 48 papers: PubMed search of Trisomy 10q • Survey of 12 Distal Trisomy 10q members 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 whichthe 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) Distal Trisomy 10q Families World Congress on Chromosome Ab.

7. History of the Syndrome • 1965: First described • de Grouchy and Canet • Chromosome 10 suspected • 1974: First diagnostic clinical picture • Yunis and Sanchez • 1983: Recognized as “Distal 10q” • Taysi (et. al.) • Proposed band q25 and q26 as responsible • 1998: First (and only) support group / website • Distal Trisomy 10q Families • Originally 6 kids - connected through UseNet postings • Grown to 25 kids (plus 2 proximal 10q) 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 3rd end piece of a “10” from the “q” arm is present. • Now there are 3 “10q” end fragments. University of Washington 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 another chromo • Most are unbalanced translocation • Missing part of other chromo • Extra piece of 10q University of Washington 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 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” • and an abnormal “9” • Now, the offspring has an unbalance transloc yielding partial trisomy 10q and partial monosomy 9q University of Washington 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) • Most papers are case studies • Expression in the patient (phenotype) • Methods of detection (cytogenics) • A few papers propose correlations between phenotype and regions of 10q Distal Trisomy 10q Families World Congress on Chromosome Ab.

13. How Often Does it Occur ? • Trisomy 21 (Down) 1 in 800 • Trisomy 18 or 13 1 in 5,000 (per synd.) • Distal Trisomy 10q 1 in 6,000,000 • “pure 10q” 1 in 12,000,000 • de novo 1 in 32,000,000 “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) Distal Trisomy 10q Families World Congress on Chromosome Ab.

14. Cumulative Case History Papers Cases Survived* 1965-70: 1 1 1 1980: 16 24 19 1990: 26 37 25 2000: 38 52 33 2003: 48 58 39 * lived past neonatal Distal Trisomy 10q Families World Congress on Chromosome Ab.

15. Where Are They • Published Reports 39 • Chromosome Deletion Outreach 4 • Distal Trisomy 10q Families 25 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. 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) Distal Trisomy 10q Families World Congress on Chromosome Ab.

17. 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 Please Meet Distal Trisomy 10q Families World Congress on Chromosome Ab.

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

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

22. A Few Smiles Ivy Emily Bryan Distal Trisomy 10q Families World Congress on Chromosome Ab.

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

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

26. Distal Trisomy 10q Families World Congress on Chromosome Ab.

27. 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 • q21  qter Moderate mental retardation and significant dysmorphism. • q11.2  qter Only some minor 10q facial dysmorphism and speech delay. 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, • Evaluate kidneys (etc.) • Hydronephrosis, dysmorphic, hydroureters • Check and watch lungs (pneumonia) • Functioning of intestines, malrotations (movement of food) 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 • Allergies • Basilar invagination ? 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. 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 Distal Trisomy 10q Families World Congress on Chromosome Ab.

33. Distal Trisomy 10q Families trisomy10q.org info@trisomy10q.org Distal Trisomy 10q Families World Congress on Chromosome Ab.