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The effect of an extra sex chromosome on language development
1. 1
The effect of an extra sex
chromosome on language
development
Dorothy V. M. Bishop
University of Oxford
2. 2
Developmental language disorders
• Family/twin studies indicate genes are important
• Nearly always have normal number of chromosomes
• Unusual to find any genetic mutation
• Likely to be like height: lots of common genetic
variants, each with small effect
Specific
language
impairment
Dyslexia Autism
Bishop, D. V. M. (2008). Specific language impairment, dyslexia, and autism: Using
genetics to unravel their relationship. In C. F. Norbury, J. B. Tomblin & D. V. M. Bishop
(Eds.), Understanding developmental language disorders: from theory to practice (pp.
67-78). Hove: Psychology Press.
4. 4
Sex chromosome trisomies
• 1960s: Newborn screening studies done to look
at unbiased samples
• Most children attend mainstream school
• But increased educational difficulties, especially
affecting language, in all three trisomies, though
with some differences in cognitive profile.
• Trisomy effects relatively mild:
– few genes on Y
– for most genes on X, all but one inactivated
Leggett, V., Jacobs, P., Nation, K., Scerif, G., & Bishop, D. V. M. (2010). Neurocognitive
outcomes of individuals with a sex chromosome trisomy: XXX, XYY, or XXY: a
systematic review. Developmental Medicine and Child Neurology, 52(2), 119-129. doi:
10.1111/j.1469-8749.2009.03545.x
6. 6
Prenatal screening
• Prenatal screening for sex chromosome
trisomies (SCTs) offered via National Health
Service in the UK for older mothers, and those
with other risk factors
7. 7
Autism, language and
communication in children with sex
chromosome trisomies
Archives of Disease in Childhood
2011
Dorothy V. M. Bishop, Angela Barnicoat, Patricia
Boyd, Debbie Shears, Alan Fryer, Katherine
Lachlan, Diana Wellesley, Patricia Jacobs, Prisca
Middlemiss, Sarah Smithson, Victoria Leggett,
Kate Nation, & Gaia Scerif.
8. 8
Measures
•Standardized parental interview :Vineland
Adaptive Behaviour Scales
•Questionnaires completed by parent,
including
Children’s Communication Checklist – 2
•Demographic/schooling information
NB. Children may not have been told about the SCT –
direct testing not possible
9. 9
N children according to chromosomes and method
of ascertainment
Group I: Recruited via prenatal screening OR joined support group when child
less than one year old (N = 10)
Group II: Joined support group, Unique, when child > 1 yr [NB no XXY from
support group]
Group I N Mean (SD) age (yr) Range
XXX 30 9.2 (3.88) 4-15 yr
XXY 19 9.4 (4.10) 4-15 yr
XYY 21 8.7 (3.48) 4-15 yr
Group II
XXX 28 10.4 (4.25) 4-17 yr
XYY 37 10.0 (3.36) 4-16 yr
Siblings
female 26 11.0 (3.38) 4-16 yr
male 42 11.4 (3.24) 4-16 yr
10. 10
Statement of special educational needs
XXX 30 5 (14%)
XXY 19 6 (32%)
XYY 21 10 (48%)
XXX 28 14 (50%)
XYY 37 29 (78%)
Siblings
XX 26 0 (0%)
XY 41 4 (10%)
National data
N SEN
Group I
Group II
Girls 3992857 199150 (5%)
Boys 3992857 456350 (11%)
Substantial
individual
variation
11. 11
Received speech and language therapy
N SALT
XXX 30 7 (24%)
XXY 19 9 (47%)
XYY 21 15 (71%)
XXX 28 17 (61%)
XYY 37 27 (73%)
Siblings
XX 26 1 (4%)
XY 41 7 (18%)
Group I
Group II
12. 12
Diagnosed with Autistic Spectrum Disorder
XXX 30 0 (0%)
XXY 19 2 (11%)
XYY 21 4 (20%)
XXX 28 0 (0%)
XYY 37 7 (19%)
Siblings
XX 26 0 (0%)
XY 41 0 (0%)
National data
N ASD
Group I
Group II
Girls 3992857 6680 (0.2%)
Boys 3992857 23760 (0.6%)
14. CCC-2: instructions
• This checklist contains a series of statements describing
how children communicate. For each statement, you are
asked to give information about the child whose name
(or code number) appears below. You are asked to
judge whether you have observed that behaviour:
• less than once a week (or never)
• at least once a week, but not every day
• once or twice a day
• several times (more than twice) a day (or always)
Norbury, C. F., Nash, M., Bishop, D. V. M., & Baird, G. (2004). Using parental checklists to identify
diagnostic groups in children with communication impairment: A validation of the Children's
Communication Checklist - 2. International Journal of Language and Communication Disorders, 39,
345-364.
15. CCC-2: sample items
scales A-D, language form/content
A: Speech. Simplifies words by leaving out some sounds, e.g. “crocodile”
pronounced as “cockodile”, or “stranger” as “staynger”
B: Syntax. (+) Produces long and complicated sentences such as: "When
we went to the park I had a go on the swings"; "I saw this man standing
on the corner"
C: Semantics. Is vague in choice of words, making it unclear what s/he is
talking about, e.g. saying “that thing” rather than “kettle”
D: Coherence. (+) Talks clearly about what s/he plans to do in the future
(e.g. what s/he will do tomorrow, or plans for going on holiday)
16. CCC-2: sample items
scales E-H, pragmatics
E: Inappropriate initiation. Talks repetitively about things that no-one is
interested in
F: Stereotyped language. Repeats back what others have just said. For
instance, if you ask, “what did you eat?” might say, “what did I eat?”
G: Use of context. Gets confused when a word is used with a different
meaning from usual: e.g. might fail to understand if an unfriendly person
was described as ‘cold’ (and would assume they were shivering!)
H: Nonverbal communication. Ignores conversational overtures from
others (e.g. if asked, "what are you making?" does not look up and just
continues working)
17. CCC-2: sample items
scales I-J, autistic-like features
I: Social relations. (+) Talks about his/her friends; shows interest in what
they do and say
J: Interests. Shows interest in things or activities that most people would
find unusual, such as traffic lights, washing machines, lamp-posts
19. 19
Why wasn’t ASD noticed in
previous studies?
• More common in prenatal than neonatal
samples? Could relate to parental age
• Children who previously would be diagnosed as
language impaired, now diagnosed with ASD:
‘diagnostic substitution’
Bishop, D. V. M., Whitehouse, A. J. O., Watt, H. J., & Line, E. A. (2008). Autism and
diagnostic substitution: Evidence from a study of adults with a history of developmental
language disorder. Developmental Medicine and Child Neurology, 50, 341-345. doi:
10.1111/j.1469-8749.2008.02057.x
20. 20
Why are communication problems
seen in all three trisomies?
Some speculations about
mechanism
21. 21
Similarities: role for neuroligins?
• Neuroligins – genes that are important for
communication between brain cells
• Currently lots of interest in possible role of
neuroligins in autism
• One neuroligin on the X chromosome, NLGN4X,
is usually NOT inactivated
• And there is a similar gene on the Y
chromosome
• Extra dose of gene product in XXX, XXY and XYY
23. 23
Neuroligins as multipliers?
• One possibility: extra dose of neuroligin could increase
the impact of genetic risk variants on other
chromosomes
• For instance, in those with 46 chromosomes, a common
form of a gene called CNTNAP2 is associated with slight
difference in language.
• Current study: We are testing whether this effect is
enhanced in those with extra X or Y
Bishop, D. V. M., & Scerif, G. (2011). Klinefelter syndrome as a window on the etiology
of language and communication impairments in children. Acta Paediatrica, 100(6), 903-
907. doi: DOI: 10.1111/j.1651-2227.2011.02150.x
24. 24
Professor Dorothy Bishop
Wellcome Trust Principal Research
Fellow,
Oxford Study of Children’s
Communication Impairments,
Department of Experimental
Psychology,
South Parks Road,
Oxford,
OX1 3UD.
http://oscci.psy.ox.ac.uk/get-involved-1/take-part