An Overview of Distal Trisomy 10q

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An Overview ofDistal Trisomy 10q

• Inaugural World Congress On Chromosome
  Abnormalities
• June 29, 2004
• Daryl Anderson
• Distal Trisomy 10q Families

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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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About this Presentation

• These slides will be on the web trisomy10q.daryla
  nderson.com
• Based on information from
• 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
• 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)

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Trisomy 10q Karyotype (Male)

• Karyotype 23 pairs of chromos 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
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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

University of Washington
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Origin of Unbalance Trans-locs

• First, a balanced translocation occurs in one
  parents karyotype when segments from two
  different chromos accidentally swap
• But the parent has a full and normal set of
  genes, and therefore is unaffected (and likely
  undetected).

University of Washington
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Continued

• Next, the child gets a set of chromos 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
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What Research Has Been Done ?

• 48 papers on 10q since 1965
• (tens of thousands on T21, 1000s 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

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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)

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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

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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.

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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 novos 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
• Jess Anderson

• Born Oct 1, 1993
• 10q25.3 ? qter de novo
• Redford, Michigan
• Josh Smith

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Jess Josh Meet --- 2002
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

• 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
Emily
Bryan
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Chromosome 10 Ideogram
From NCBI.NIH.COM Website
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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.

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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.

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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,
• Evaluate kidneys (etc.)
• Hydronephrosis, dysmorphic, hydroureters
• 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?

• 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.

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Appreciation

• Families that participated in the survey
• Congress organizers
• HP-IPG Research Library Corvallis, OR
• Kory Keller of OHSU -- Consulting
• Chromosome Deletion Outreach

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Distal Trisomy 10q Families

• trisomy10q _at_ darylanderson . com
• trisomy10q . darylanderson . com