An Overview of
Distal Trisomy 10q
Inaugural World Congress On Chromosome Abnormalities June 29, 2004
Daryl Anderson Distal Trisomy 10q Families
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Overview & Goals
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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April 8, 2004
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About this Presentation
These
slides will be on the web trisomy10q.darylanderson.com on information from
Based
48 papers: PubMed search of Trisomy 10q Survey of 12 Distal Trisomy 10q members
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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)
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History of the Syndrome
1965: First described
de Grouchy and Canet Chromosome 10 suspected Yunis and Sanchez
1974: First diagnostic clinical picture
1983: Recognized as “Distal 10q”
Taysi (et. al.) Proposed band q25 and q26 as responsible
Distal Trisomy 10q Families Originally 6 kids - connected through UseNet postings Grown to 25 kids (plus 2 proximal 10q)
Distal Trisomy 10q Families
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1998: First (and only) support group / website
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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.
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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
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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).
Distal Trisomy 10q Families
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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
Distal Trisomy 10q Families
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What Research Has Been Done ?
48
papers on 10q since 1965 papers are case studies
(tens of thousands on T21, 1000’s on T18) Expression in the patient (phenotype) Methods of detection (cytogenics)
Most
A
few papers propose correlations between phenotype and regions of 10q
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How Often Does it Occur ?
21 (Down) Trisomy 18 or 13
Distal
Trisomy
1 in 800 1 in 5,000
(per synd.)
Trisomy 10q “pure 10q” de novo
1 in 6,000,000 1 in 12,000,000 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)
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Cumulative Case History
Papers 1965-70: 1 1980: 16 1990: 26 2000: 38 2003: 48 Cases 1 24 37 52 58 Survived* 1 19 25 33 39
* lived past neonatal
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Where Are They
Published Reports Chromosome Deletion Outreach Distal Trisomy 10q Families
39 4 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.
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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)
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Please Meet
Born: Oct 1, 1993 10q25.3 qter de novo Corvallis, Oregon
Born: Oct 1, 1993 10q25.3 qter de novo Redford, Michigan
Jess
Anderson
Josh
Smith
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Jess & Josh Meet --- 2002
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Henry Ford Museum
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Stupid Math Trick Revisited
Answer: 1 in 2,850
(in a given year)
1 in (1/8 de novo per year / 365)^2 * 365
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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
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Features of the Syndrome
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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
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A Few Smiles
Ivy
Distal Trisomy 10q Families
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Emily
Bryan
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Chromosome 10 Ideogram
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From NCBI.NIH.COM Website April 8, 2004
Segments vs. Phenotype
(approximate*)
10q26
Facial Dysmorphism, mental and growth retardation Mild vision, hearing, and speech issues Heart and Kidney issues Ocular issues
10q25
10q24
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
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Notes on Following Charts
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.
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Heart Issues vs. Extra 10q Segment in Specific Individuals
ID Num
Extra 10q segment
22.1 22.2 22.3 23.1 23.2 23.31 23.32 23.33 24.1 24.2 24.31 24.32 24.33 25.1 25.2 25.3 26.11 26.12 26.2 26.3
1000 Gray - Negative of issues 1003 Green - Positive for issues 1004 1009 1012 1014 1018 1019 1022 1024 1026 Tonk, 1996 chen, 2003 James 2003 Tuysuz, 2000 chen 1999 hypertrophic cardiomyopathy vsd vsd, asd, pda, subaortic membrane Grade II/IV systolic ejection murmur at left parasternal border q24.2 -- q24.3 asd vsd (2 each), asd (2 each), all but one vsd resolved by 2.5yrs vsd
q25.3 --> qter q25.2-25.3 --> qter q25.1 --> qter q24.3 --> qter q25.1 --> qter q24.3 --> qter q25.3 --> qter and partial mono q7 dup of q26 q22.3 --> qter q22 --> qter q26.2-->qter
q24.1 --> qter and part. mono q22 q25.2 --> qter and part.mono 6p q22.3 --> qter and part. Mono 20p q24.1 --> qter and part. mono q22
ID Number relates to children in Distal Trisomy 10q Families.
Generally their info is from direct survey. Other data is from papers ID'ed by auther and date.
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Kidney Issues vs. Extra 10q Segment in Specific Individuals
ID Num
Extra 10q segment
22.1 22.2 22.3 23.1 23.2 23.31 23.32 23.33 24.1 24.2 24.31 24.32 24.33 25.1 25.2 25.3 26.11 26.12 26.2 26.3
1000 Gray - Negative of issues 1003 Green - Positive for issues 1004 1009 1012 1014 1018 1019 1022 1024 1026 Tonk, 1996 Chen, 2003 James 2003 Tuysuz, 2000 Chen, 1999 hypertrophic cardiomyopathy bilateral hydronephrosis, dysmorphic but functioning well multicystic kidneys q24.2 -- q24.3 Increased echogenicity of renal parenchyma bilateral hydronephrosis, hydroureters Two kidneys fused together on one side.
q25.3 --> qter q25.2-25.3 --> qter q25.1 --> qter q24.3 --> qter q25.1 --> qter q24.3 --> qter q25.3 --> qter and partial mono q7 dup of q26 q22.3 --> qter q22 --> qter q26.2-->qter
q24.1 --> qter and part. mono q22 q25.2 --> qter and part.mono 6p q22.3 --> qter and part. Mono 20p q24.1 --> qter and part. mono q22
Distal Trisomy 10q Families
ID Number relates to children in Distal Trisomy 10q Families.
26 World Congress on Chromosome Ab. Generally their info is from direct survey.
Other data is from papers ID'ed by auther and date.
April 8, 2004
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.
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Treatments and Watch List
Soon After Birth Evaluate heart
ASD,VSD,PDA,sub-aortic membrane, ejection murmur, hypertrophic cardiomyopathy, Hydronephrosis, dysmorphic, hydroureters
Evaluate kidneys (etc.)
Check
and watch lungs (pneumonia) Functioning of intestines, malrotations (movement of food)
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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 ?
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What is Needed?
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.
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Treatments
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Appreciation
that participated in the survey Congress organizers HP-IPG Research Library Corvallis, OR Kory Keller of OHSU -- Consulting Chromosome Deletion Outreach
Families
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Distal Trisomy 10q Families
trisomy10q @ darylanderson . com trisomy10q . darylanderson . com
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