Language impairment in the 22q11 deletion syndrome

Developmental language impairments have a profound impact on an individual*s
life. Difficulties in acquiring a native language can result from unfavorable
physical, psychological, social or educational conditions. In addition,
approximately 7% of all children show severe and persistent delays in language
skills without any obvious neurological, psychological or social causes. This
condition is called specific language impairment (SLI). SLI is diagnosed by
exclusion; there is no unambiguous clinical marker. Consequently, the SLI
population is heterogeneous, and this hampers efforts to elucidate the pathway
from (genetic) cause, via neurocognitive deficits to impaired language. An
approach that is expected to bring new insights is to compare SLI with the
22q11.2 deletion syndrome (22q11DS). Virtually all children with 22q11DS show
severe language delays in the early stages of development. This leaves room for
the hypothesis that the language delays in 22q11DS are a self-contained
symptom, unrelated to any of the other known physical or psychological
symptoms. If so, the 22q11DS population shares a characteristic with the SLI
population. In contrast to SLI, 22q11DS has a uniform genetic etiology - a
microdeletion in the long arm of chromosome 22 - which also provides for an
unmistakable clinical marker, which can be detected at an early age. Our
current knowledge about the development of language in 22q11DS is limited and
direct comparisons with SLI have not yet been made. The present study aims to
fill this void by performing an in-depth longitudinal comparison of language
development in young children with 22q11DS and age-matched children with SLI.
SLI has been associated with specific neurocognitive deficits, particularly
with regard to short-term and working memory, executive functions, and implicit
learning. If the language difficulties in 22q11DS are similar in nature to
those seen in SLI, we expect to also see similar neurocognitive deficits in the
22q11DS population. For this reason we will study the neurocognitive profles of
both populations and relate these to their developmental language profiles.
This study will thus yield new knowledge on (disordered) development of
language in children with 22q11DS and its neurocognitive underpinnings. This
study will not only enhance our understanding of the 22q11DS phenotype, but can
also be used to improve speech-language diagnostics and prognostics in this
population, which in turn will have positive impact on counseling
parents/caretakers, and managing their expectations with regard to child*s
condition.

The first objective of this study is to provide a detailed, quantitative and
qualitative description of early language development (*developmental language
profile*) in children with 22q11DS, comprising expressive and receptive
abilities, covering all levels of linguistic structure (sounds, words,
grammar), as well as the use of language in conversation and narration. This
developmental language profile will be compared to that of children with SLI,
so as to determine whether the two populations are phenotypically similar, as
well as to the developmental language profile of healthy, typically developing
children.

The second objective is to determine if children with 22q11DS and children with
SLI show deficiencies in short-term and working memory, executive function, or
implicit learning, and to assess the degree to which such deficiencies are
(causally) related to language impairments in these populations.

Longitudinal observational case-control study, involving three groups of
children.

No immediate benefits are expected for the participants in this study. The
results of this study will enhance our understanding of the 22q11DS phenotype,
and are also expected to be an impetus for improving speech-language
diagnostics and prognostics in this population. In addition, the results may be
conducive to improving advising parents/caretakers, and managing their
expectations with regard to their child*s condition.
The instruments and procedures used are routinely employed by psychologists and
linguists studying the development of language and its neurocognitive
underpinnings. There are no known risks. The burden imposed on participants and
their parents/caretakers is related to the time investment they are asked to
make: the study involves 1 to 5 assessment sessions, three of which will take
1,5 hours (2 x 45 min.), one which will take 45 minutes, and one of which will
take between 45 and 75 minutes spread out over a period of 4;8 year for
children with 22q11DS. For children with SLI the study involves 1 to 3
assessment sessions, of which only the first will take 1,5 hours (2 x 45 min.)
and the second and third will take 45 minutes, spread out over a period of max.
1 year. For controls the study involves 1 to 4 assessment sessions, of which
only the first and fourth will take 1,5 hours (2 x 45 min.) and the second and
third will take 45 minutes, spread out over a period of 4;8 year. As our
research questions concern the development of a complex, multifaceted cognitive
capacity, i.e., changes in ability as a function of age, a design that is less
burdensome is not possible. To reduce the burden on participants and their
parents/caretakers we have reduced the number of test procedures and test
sessions as much as possible. Clearly, the age range of the participants is
dictated by the phenomenon under study, primary language acquisition and
development.