An Overview of Distal Trisomy 10 q Inaugural

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

Addendum Ø 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 10 q Families World Congress on Chromosome Ab. 2 April 8, 2004

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

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

What is Distal Trisomy 10 q ? Ø Distal Trisomy 10 q is an extremely rare chromosomal disorder in which the end (distal) portion of the long arm (q) of one chromosome 10 (10 q) 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 10 q Families World Congress on Chromosome Ab. 6 April 8, 2004

History of the Syndrome Ø 1965: First described l l Ø 1974: First diagnostic clinical picture l Ø Yunis and Sanchez 1983: Recognized as “Distal 10 q” l l Ø de Grouchy and Canet Chromosome 10 suspected Taysi (et. al. ) Proposed band q 25 and q 26 as responsible 1998: First (and only) support group / website l l l Distal Trisomy 10 q Families Originally 6 kids - connected through Use. Net postings Grown to 25 kids (plus 2 proximal 10 q) Distal Trisomy 10 q Families World Congress on Chromosome Ab. 7 April 8, 2004

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

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

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… Ø But the parent has a full and normal set of genes, and therefore is “unaffected” (and likely undetected). Ø Distal Trisomy 10 q Families World Congress on Chromosome Ab. University of Washington 10 April 8, 2004

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

What Research Has Been Done ? Ø 48 papers on 10 q since 1965 l (tens of thousands on T 21, 1000’s on T 18) Ø Most papers are case studies l l Expression in the patient (phenotype) Methods of detection (cytogenics) Ø A few papers propose correlations between phenotype and regions of 10 q Distal Trisomy 10 q Families World Congress on Chromosome Ab. 12 April 8, 2004

How Often Does it Occur ? Ø Trisomy 21 (Down) 1 in 800 1 in 5, 000 Ø Trisomy 18 or 13 Ø Distal Trisomy 10 q (per synd. ) 1 in 6, 000 1 in 12, 000 1 in 32, 000 “pure 10 q” l de novo l “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 10 q Families World Congress on Chromosome Ab. 13 April 8, 2004

Cumulative Case History Papers 1965 -70: 1 1980: 16 1990: 26 2000: 38 2003: Cases 1 24 37 52 48 58 Survived* 1 19 25 33 39 * lived past neonatal Distal Trisomy 10 q Families World Congress on Chromosome Ab. 14 April 8, 2004

Where Are They Published Reports Ø Chromosome Deletion Outreach Ø Distal Trisomy 10 q Families Ø Total (after duplications removed) 39 4 25 ~ 62 Note: There are certainly more, but these are the ones known in the research and to the single Trisomy 10 q support organization. Distal Trisomy 10 q Families World Congress on Chromosome Ab. 15 April 8, 2004

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 10 q Families World Congress on Chromosome Ab. 16 April 8, 2004

Please Meet Ø Born: Oct 1, 1993 Ø 10 q 25. 3 qter de novo Ø Corvallis, Oregon Ø Ø Jess Anderson Ø Josh Smith Distal Trisomy 10 q Families World Congress on Chromosome Ab. Born: Oct 1, 1993 Ø 10 q 25. 3 qter de novo Ø Redford, Michigan 17 April 8, 2004

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

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 10 q Families World Congress on Chromosome Ab. 19 April 8, 2004

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

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

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

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

Segments vs. Phenotype (approximate*) Ø 10 q 26 l Ø 10 q 25 l Ø Facial Dysmorphism, mental and growth retardation Mild vision, hearing, and speech issues 10 q 24 l l Heart and Kidney issues Ocular issues 10 q 23 Ø 10 q 22 Ø l l Severe ocular issues Dysmorphism of limbs * Based on small set of data. Cases with little or no associated partial monosomy. Distal Trisomy 10 q Families World Congress on Chromosome Ab. 24 April 8, 2004

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

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

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

Segments vs. Phenotype Major exception: Translocation onto chromosome X can “inactivate” significant segments of 10 q, resulting in no, or milder symptoms. Examples: l l l q 23. 3 qter No features of 10 q q 21 qter Moderate mental retardation and significant dysmorphism. q 11. 2 qter Only some minor 10 q facial dysmorphism and speech delay. Distal Trisomy 10 q Families World Congress on Chromosome Ab. 28 April 8, 2004

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

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

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

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

Distal Trisomy 10 q Families trisomy 10 q. org info@trisomy 10 q. org Distal Trisomy 10 q Families World Congress on Chromosome Ab. 33 April 8, 2004