COGNITIVE AND DEVELOPMENTAL FEATURES OF CHILDREN WITH
DYSGENESIS OF THE CORPUS CALLOSUM
Megan Kovac
A thesis submitted to the faculty of the University of North Carolina at Chapel Hill in
partial fulfillment of the requirements for the degree of Master of Arts in the
Department of School Psychology.
Chapel Hill
2011
Approved by:
Rune J Simeonsson, Ph.D.
Stephen Hooper, Ph.D.
Rebecca Pretzel, Ph.D.
ABSTRACT
MEGAN KOVAC: Cognitive and Developmental Features of Children with
Dysgenesis of the Corpus Callosum
(Under the direction of Rune J Simeonsson)
The corpus callosum is the brain structure that divides the right and left
hemispheres. It consists of approximately 200 million neural fibers and is responsible
for interhemispheric transfer of information and higher-order cognition. Congenital
agenesis of the corpus callosum (ACC) is a condition that involves partial or
complete absence of the corpus callosum from birth (i.e., not acquired). A systematic
review of the literature on neurocognitive and neurodevelopmental outcomes among
children and adolescents with ACC from 1969 through 2011 was conducted, and two
hundred seventy-four studies were selected for initial review. Specific studies are
described in this paper, and the salient findings are discussed. The findings are then
contextualized within the framework of the International Classification of
Functioning for Children and Youth in order to summarize the research and illustrate
the utility of that instrument. Implications for future research and clinical practice are
discussed.
ii
TABLE OF CONTENTS
LIST OF TABLES.................................................................................v
LIST OF FIGURES................................................................................vi
Chapter
I.
INTRODUCTION................................................................1
The Typical Corpus Callosum..............................................1
Agenesis and Dysgenesis of the Corpus Callosum...............3
Etiology.................................................................................5
Incidence and Prevalence......................................................6
Significance of a Review on Congenital ACC......................8
Research Questions................................................................9
II.
METHODS............................................................................11
Selection Criteria...................................................................11
Aggregation of Articles.........................................................13
Background and Relevance of the ICF-CY...........................14
III.
RESULTS..............................................................................16
Case Studies...........................................................................16
Quasi-Experimental Studies..................................................20
Descriptive Studies................................................................23
iii
Review Papers.......................................................................27
Additional Findings...............................................................29
Alignment of Reviewed Features with IFC-CY
Framework.............................................................................29
IV.
DISCUSSION.......................................................................34
Cognitive and Developmental Features of Children with
Congenital ACC....................................................................34
Application and Implications of the ICF-CY for Research
and Clinical Practice.............................................................37
Limitations............................................................................37
Directions for Future Research.............................................38
REFERENCES..................................................................................41
iv
LIST OF TABLES
Table
1.
Table 1: Selected Case Studies........................................................17
2.
Table 2: Selected Quasi-Experimental Studies................................20
3.
Table 3: Selected Descriptive Studies..............................................24
4.
Table 4: Selected Review Papers.....................................................27
5.
Table 5: ICF-CY Body Functions Indicated in ACC Research.......32
6.
Table 6: ICF-CY Body Structures Indicated in ACC Research.......32
7.
Table 7: ICF-CY Activities and Participation Indicated
in ACC Research..............................................................................33
v
LIST OF FIGURES
Figure
1.
Figure 1: Intact corpus callosums.......................................2
2.
Figure 2: Regions of intact corpus callosum.....................2
3.
Figure 3: Images of Dysgenesis.........................................5
4.
Figure 4: Selection Method Decision Tree........................12
5.
Figure 5: Decision Tree with Results................................15
vi
ABBREVIATIONS
ACC
DCC
Agenesis of the corpus callosum
Dysgenesis of the corpus callosum
vii
CHAPTER 1
INTRODUCTION
The Typical Corpus Callosum
The corpus callosum is a band of approximately 200 million neural fibers that
connects the left and right cerebral hemispheres. It begins to develop around the 12th
week of gestation and matures through a complex process of neuronal migration,
development, and eventual neuronal pruning (Paul, 2007). By week 20, the corpus
callosum can be seen on a sonogram or fetal MRI (Cignini et al., 2010). Although the
corpus callosum may be considered fully developed by around age 4, as with most
neural structures, it likely continues to change over the lifespan (Keshavan et al.,
2002).
Figure 1 shows a sagittal view of a brain. The white band in the center of the
brain is the corpus callosum. It is located between the right and left hemispheres and
it is comprised entirely of white matter. The corpus callosum has traditionally been
viewed as having five distinct parts: the rostrum, genu, anterior midbody, isthmus,
and splenium (Witelson, 1989). These segments are identified in Figure 2. We still
have much to learn about the role and function of the corpus callosum, but it is well
accepted that its primary role is to facilitate communication between the hemispheres,
using both inhibitory and excitory interhemispheric transfer (e.g., Gazzaniga &
Sperry, 1967; Bogen, 1969; Sperry et al., 1969). Most of what we know about how
the corpus callosum functions has come out of research conducted with people who
have unusual or absent callosal development.
Figure 1: Intact corpus callosums
Images from:
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/hypopit/anatomy.html and
http://bobschuster.com/case-studies/brain-injury-facts/
Figure 2: Regions of intact corpus callosum
Images from: http://emedicine.medscape.com/article/407730-overview
2
Agenesis and dysgenesis of the corpus callosum
Agenesis of the corpus callosum (ACC) is a condition in which the corpus
callosum fails to develop fully (dysgenesis or partial ACC) or at all (complete or total
ACC). ACC can occur as a secondary symptom, caused by malformations of the
central nervous system such as neural tube defects, lissencephaly, and
holoprosencelphay (Glass et al., 2008). It can occur as a comorbidity with, or
characteristic symptom of, a number of chromosomal abnormalities (e.g., Aicardi
syndrome, Andermann syndrome). A third possible presentation is congenital,
isolated ACC, where the absence of the corpus callosum is the primary feature of
maldevelopment and it is present from birth (i.e., not a result of lesions or surgical
procedures). The latter is likely quite rare but reliable estimates of incidence have
been difficult to obtain since individuals can be asymptomatic and research is
dominated by clinical samples (which are subject to bias).
Dysgenesis of the corpus callosum, most frequently referred to as partial agenesis,
occurs when the corpus callosum is partially formed. The most common presentation
of partial ACC is when the anterior portions of the corpus callosum are present (i.e.,
the rostrum and the genu) and the posterior areas fail to develop (i.e., the isthmus and
the splenium). For a while, the prevalence of this presentation was taken as evidence
that the corpus callosum develops from front to back. Recently this view has been
challenged (Thompson, Giedd, Woods, Macdonald, Evans & Toga, 2000) and it has
been proposed that the center body of the corpus callosum develops first and growth
proceeds simultaneously in both directions. Improving our understanding of how the
corpus callosum develops will shed light on the etiologies of ACC (particularly with
3
regard to the impact of early neuronal migration). Additionally, it will help
understand the significance of structures that are considered potential "alternative
pathways" for interhemispheric transfer, such as Probst bundles. Probst bundles refer
to a collection of fibers that can develop longitudinally, next to or in place of the
corpus callosum. It has been observed in subjects with ACC, and it has been
hypothesized that it may correlate with improved developmental outcomes (Corballis,
2004).
The majority of the literature has found that outcomes are better for individuals
with dysgenesis of the corpus callosum (compared to individuals with complete
ACC), though there is some conflicting evidence (Moutard et al., 2003). Moderate
evidence suggests that the presence of the anterior commisure (which consists of the
rostrum and the genu) correlates with better cognitive and/or developmental
functioning, though very few child studies have documented the degree of dysgenesis
or which segments of the corpus callosum are present in the study participants.
Figure 3 provides a side-by-side comparison of an intact corpus callosum, dysgenesis
of the corpus callosum (with the anterior body preserved), and complete agenesis.
4
Figure 3: Images of Dysgenesis
Intact CC
Partial ACC
Complete ACC
Images from: http://emedicine.medscape.com/article/407730-overview
Etiology
The origins of ACC are genetic syndromes, karyotypic abnormalities, and
metabolic disorders. [Readers may be directed to Paul, 2007 for a thorough
discussion of the research that describes how these conditions contribute to the
dysgenesis of the corpus callosum.] At least one study has investigated
environmental factors as potential predictors or correlates of ACC (Glass et al.,
2008). Fetal insults, particularly fetal alcohol syndrome, have been implicated in
hypoplasia (thinning) of the corpus callosum, but they have not been linked to ACC.
There may be a hereditary component to at least one etiology of ACC, as numerous
studies reviewed for this article (i.e., 14) have family members (i.e., siblings, parents
and children, cousins) in their sample.
Although the above etiologies have been identified, research has not been
successful in establishing the etiology of ACC in the majority of non-genetic cases.
Schell-Apacik et al. (2008) examined data from 172 individuals with documented
5
abnormalities of the corpus callosum. Forty-one patients were confirmed to have
ACC or partial dysgenesis. Chromosomal, subtelomere, and molecular genetic
testing were utilized to determine the etiology of the dysgenesis, but etiology could
only be confirmed for approximately 13 (32%) of the 41 cases (17 ACC and 11
dysgenesis could not be determined). Similarly, Shevell (2002) was able to determine
etiology for only 45.8% of cases. That study analyzed the factors that predicted
successful determination of etiology and found that cerebral dysgenesis and moderate
to severe developmental delay were significant predictors (χ2=7.464, P=.006 and
χ2=3.962, P=.05, respectively).
The significance of these relatively unsuccessful efforts to correlate etiology with
outcomes in callosal dysgenesis speaks to the importance of establishing a catalogue
of functioning for children with ACC. Whether it is due to limitations in the
molecular or genetic testing available to us at this time or the nature of callosal
dysgenesis, studies that focus on linking etiology with outcomes in ACC are largely
unsuccessful and, consequently, offer limited utility to clinicians who aim to serve
this population now. These types of studies are at the early stages of informing the
field about the etiologies of ACC; however, they have limited clinical utility at this
time. Emphasis should be placed on researching measurable/observable features in
less biased samples in order to gain a clearer understanding of how these children
develop and what interventions may support their optimal development.
Incidence and Prevalence
6
The vast majority of studies cite the prevalence of ACC as 2-3% among people
with developmental disabilities (Jeret, Serur, Wisniewski, & Lubin, 1987). It is much
harder to estimate the incidence or prevalence rates for the non-disabled population
because of sample bias. Reasonable estimates place the incidence among the general
population between .4% (Jeret et al. 1987) and .7% (Reynolds & Fletcher-Janzen,
2009 ). Most studies rely on data from clinical samples (i.e., people who have come
to the clinic/hospital for services). Even a population-based study published in 2008
could not provide an entirely bias-free estimate because the data were pulled from a
registry of birth defects (Glass, Shaw, Ma, & Sherr, 2008). If there was a way to
ascertain unbiased estimates of the incidence or prevalence of ACC, it may be a moot
point given the observation that ACC can be asymptomatic. Progress in ultrasound
technology and training may provide the greatest hope of finding unbiased estimates
of incidence and prevalence. Other estimates of prevalence rates in the literature
include: 0.1-0.3% in unselected hospital population (Larson & Osborn, 1982); 1.6%,
determined from consecutive MRIs at a pediatric referral center (Bodensteiner et al.,
1994); 0.07% of consecutive MRIs completed for non-urgent cases (Bodensteiner et
al., 1994); 0.35% in a review of data from 1991 to 2001 from a pediatric neurology
provider (total of 6911 cases) (Shevell, 2002). Studies that have utilized postmortem
data tend to find high prevalence rates of ACC, which makes sense since ACC is
often one indication of more complicated/involved impairment (Fratelli,
Papageorghiou, Prefumo, Bakalis, Homfray, & Thilaganathan, 2007).
ACC may be more common in males than females. In the study by Shevell
referenced above (2002) 62.5% of the sample was male. Samples generally have
7
higher numbers of male participants, though the differences are not statistically
significant.
Significance of a Literature Review on Congenital ACC
The research literature on ACC is characterized by small sample sizes,
heterogeneous samples, single-subject clinical case studies, and diverse theoretical
paradigms. A comprehensive review that pays particular attention to the quantity,
design, and purpose of the literature on ACC is essential for advancing our
knowledge about this intriguing anomaly.
ACC has been broadly conceptualized in research and clinical practice. The term
has been used to describe patients who have had their corpus callosums surgically
removed or severed, individuals who have abnormally or incompletely formed corpus
callosums due to genetic, metabolic, or environmental conditions, and individuals for
whom the corpus callosum has completely failed to develop for reasons we do not yet
understand. Although evidence that these are physiologically and functionally
distinct groups has been available since the early 1970s, they are still often studied
together. This broad grouping reflects the enthusiasm researchers have felt for
exploring abnormalities of the corpus callosum, as well as the challenge of finding
these cases. A rare, potentially asymptomatic condition like ACC presents significant
challenges because subjects are difficult to identify, recruit, and retain for
longitudinal follow-up.
At this point, though, the tools required to accelerate research on ACC are more
sophisticated and accessible than ever before. From a clinical or applied perspective,
8
there is an expectation that practitioners should be prepared to advise parents
regarding developmental trajectories, interventions, and support networks for children
with ACC. Now is the time to thoroughly and systematically analyze what we know
from the last forty years of research, and identify the most effective methodological
approaches to guide our investigations moving forward. The goal of this paper is to
review the research on ACC, with particular attention to the neurocognitive features
for children and adolescents. Once that has been accomplished, the findings will be
presented within the context of a functional tool, the ICF-CY, and the implications of
using that tool in this way will be discussed.
Research Questions
ACC is a condition with a diverse spectrum of etiologies, presentations, and
outcomes, but one theme can be found in every study or paper on the topic: the
existing research is characterized by heterogeneous samples, small sample sizes,
diverse research questions, and few experimental designs. This is a general statement
that permeates this literature. Consequently, those who aim to understand the clinical
implications of ACC and the role of the corpus callosum in brain functioning tend to
draw from research with very different aims and designs. The first goal of this paper
is to describe the research on congenital agenesis of the corpus callosum in children
and adolescents; until we address what really comprises the research that has already
been done, it is difficult to move forward in the most efficient way. It is important to
outline how many studies have investigated congenital agenesis of the corpus
callosum; how many have used retrospective, prospective, and longitudinal data; how
9
many have looked at neuropsychological functioning; and how many have used
experimental designs. Assessing the body of research in this way will allow us to
more accurately consider what we know and how we have come to know it. This
process will enable us to highlight the salient findings on cognitive and
developmental characteristics of children with ACC.
The second objective of this paper is to apply a globally recognized system of
functional development to the findings on ACC in order to efficiently summarize the
paper's findings and illustrate the utility of this tool. The International Classification
of Functioning, Disability and Health for Children and Youth (ICF-CY) is a universal
catalogue of functioning that enables researchers, clinicians, and policy-makers to
describe the functional capacities of children in a person-focused, actionable way.
We will apply this approach to the research reviewed in this paper, thereby
establishing a comprehensive (albeit preliminary) picture of how children with ACC
are functioning in their daily lives. The implications for future research and
therapeutic intervention will be discussed in this context.
10
CHAPTER 2
METHODS
Selection Criteria
Our first research question was to examine the nature and findings of the research
literature on congenital ACC in children and adolescents. In order to achieve this
goal, a systematic review of the literature was conducted using three databases: Psych
Info, Pub Med, and Pub Health. Search terms included "agenesis," "callosum," and
"agenesis corpus callosum." Studies that were published between 1969 and 2010 and
addressed cognition and/or development in children with ACC were reviewed.
Exclusion criteria for the initial search were: non-English speaking journals, animal
studies, dissertations, and book chapters. The parameters for the initial search were
kept broad since one of the aims of this paper is to establish how broad the human
literature on agenesis is. When we consider the number of results returned from the
first search and compare it to what remains when the criteria are narrowed down to
our target area of developmental features for children with congenital ACC, we can
see how great the need for focused research is.
Studies were then reviewed for sample characteristics and studies that were not
child-focused were excluded. In order to qualify as a child-focused study, at least
51% of the sample had to be 21 years of age or younger or age had to be considered
as a variable in some way. The remaining studies were classified as case studies,
quasi-experimental studies, descriptive studies, or review papers (classification
criteria are explained below). Finally, each category of child studies was reviewed
for sample characteristics and the degree of emphasis placed on cognitive or
developmental features. These are referred to as selected studies throughout the
paper. Figure 4 illustrates this process with a decision tree.
Figure 4: Selection Method Decision Tree
ACC
Studies
ACC
Child
Studies
Case
Studies
Quasi‐
Experimental
Studies
Descriptive
Studies
Review
Papers
Selected
Case
Studies
Selected
Quasi‐
Experimental
Studies
Selected
Descriptive
Studies
Selected
Review
Papers
For the purposes of this paper, cognitive features refers to intellectual or
neuropsychological functioning (e.g., executive functioning, memory). Studies that
address specific academic skills, such as phonological processing were included since
that information can be understood in a neuropsychological context (i.e.,
developmental dyslexia). Developmental features refers to adaptive skills (e.g., daily
12
living, self-care, communication), early developmental milestones, and
socioemotional or psychosocial development. Studies with particularly interesting
designs and relevant conclusions are highlighted in this paper, in addition to the
overall findings regarding neurodevelopmental features of children with ACC.
Aggregation of Articles
Studies were categorized as reviews, clinical case studies, quasi-experimental
studies, or descriptive studies. These categories are loosely based on the constructs
provided by Morgan, Gliner, and Harmon (2006). Clinical case studies comprised the
majority of the results returned in the search. They focus on a small number of
subjects who are grouped together because of similar symptoms, diagnosis, or genetic
affiliation. They describe clinical profiles, phenotypes, and genotypes of individuals
with extraordinary presentations. Some case studies include information about a
subject's performance on specific tasks, but that information is still considered
descriptive as the tasks are not performed in a controlled experimental environment.
For the purposes of this paper, quasi-experimental studies compare performance
between or among groups of individuals. Group assignment may be based on ACC
status (presence, absence, or degree of dysgenesis). Since group assignment is not
random, we refer to these studies as quasi-experimental. In order to be placed in this
category designs must include some kind of control.
Descriptive studies describe characteristics or performance of individuals with
ACC, but there is no control in the design. Retrospective studies, prospective studies,
surveys, observations, and performance on tasks (without controls) are included in
13
this category. Finally, review papers are retrospective examinations of research on
ACC.
Background and Relevance of the ICF-CY
The second goal of this paper is to apply the ICF-CY to the information reviewed
on ACC in order to summarize the findings and illustrate the utility of this
classification system. The International Classification of Functioning, Disability and
Heath for Children and Youth (ICF-CY) is a system of recording the functional
capacity of children within the context of their environment. The creation of the ICFCY was sponsored by the Worth Heath Organization and designed collaboratively by
experts and advocates from various countries in order to establish a common method
for describing the developmental experience of children around the globe. It was
published in 2007 and has been endorsed by all member-countries of the World
Health Organization.
The application of the ICF-CY is particularly germane to this paper because it
provides a way of discussing child development and disability that is based on
structure and function. Rather than assigning a label (i.e., diagnosis) which carries
with it a list of characteristics that may or may not be present, and which may be
present in varying degrees, the ICF-CY offers an efficient way to describe a profile of
functional ability or impairment. ACC is a condition that occurs in children with a
myriad of cognitive and developmental outcomes. Although we should continue to
work toward a better understanding of the prognosis and trajectory for children with
ACC, using an approach that provides a comprehensive picture of their individual and
14
overall functioning is critical. The ICF-CY can help the research on ACC progress in
two specific ways: (1) it will refine our understanding of the aspects of the brain and
developmental functioning that are affected by ACC; and (2) it will help us recognize
trends that can inform the prognosis and intervention planning for children with ACC.
15
CHAPTER 3
RESULTS
Figure 5: Decision Tree with Results
ACC
Studies
N=273
ACC
Child
Studies
N=126
Case
Studies
N=52
Selected
Case
Studies
N=12
Quasi‐Experimental
Studies
N=19 Selected
Quasi‐
Experimental
Studies
N=9
Descriptive
Studies
Review
Papers
N=51
N=4
Selected
Descriptive
Studies
N=20
Selected
Review
Papers
N=2
Case Studies
Our first objective was to describe the literature on cognitive and developmental
features of children with ACC. The results of the literature review will be presented
in the aforementioned categories and summarized in the Discussion section.
Fifty-two clinical case studies were identified as addressing issues related children
with agenesis of the corpus callosum. Many of these studies describe complex cases
of children with multiple comorbidites, so the sample was narrowed down based on
two factors: (1) whether ACC was a primary feature and (2) whether attention was
paid to neurodevelopmental or neurocognitive functioning. Twelve selected case
studies are described in Table 2.
Table 1: Selected Case Studies
Author
Filges et al.
(2010)
Sample
n=1, fetally diagnosed
with ACC
Measures
Genetic testing
and observation
Liasis,
Hildebrand,
Clar, Katz,
Gunny,
Stieltjes, &
Taylor (2009)
Parraga,
Parraga, &
Jensen (2003)
n=1, age 4 yrs.
holoprosencephaly
(HPE) and ACC
Visual, auditory,
and somatosensory
evoked potentials
and imaging
n=2, congenital ACC
was
incidental finding
MRI
Panos, Porterb,
Panosb,
Gainesc, &
Erdbergd
(2001)
n=1, age 11 yrs.
hospitalized for
extreme behavioral
disturbance
MRI revealed
complete ACC
(segment of rostrum
preserved)
MRI, WISC III,
Tactual
Performance Test,
Rey-Osterrieth
Complex Figure,
Developmental
Test of VisualMotor Integration,
Wisconsin Card
Sorting Test, Wide
Range
Achievement Test
17
Findings
Examined relationship between
genetic deletions and phenotype;
found a 5.45 Mb deletion within
1q42 was found to cause this
phenotype; overlap with the
microdeletion 1q41q42 syndrome;
suggests gene interaction during
embryonic development may lead to
syndromes characterized by
malformation
Human face stimuli provoked
greater response than pattern;
auditory response to speech and
tones were observed in the frontal
regions; no response to
somatosensory stimulation
Advocates for comprehensive
neuropsychiatric evaluation for
children with severe behavior
problems; cites uncertainty
regarding prevalence of ACC in
children with behavioral challenges
and normal intelligence
Applied Rourke's Nonverbal
Learning Disorder model; found that
subjects impairment was consistent
with but not fully explained by the
NLD model; ACC may contribute to
additional/severe deficits in verbal
learning, auditory attention, and
verbal expression
III, Beery Picture
Vocabulary Test,
California Verbal
Learning TestChildren's Version
Inter-hemispheric
transfer,
psychometric
measures, and
motor and
cognitive function
Finlay et al.
(2000)
n=3, age 11, 12 & 39
yrs.
(Mother and two
daughters)
Corballis and
Finlay (2000)
n=3, aged 11, 12 & 39
yrs.
(same sample as
above)
Color, letter, word,
presentation to
visual fields
Brown & Paul
(2000)
n=2, age 16 and 21
yrs.
Temple (1993)
n=3, age 9-15 yrs.
Temple,
Jeeves,
Vilarroya
(1990)
n=2, age 9 and 13 yrs.
WISC-R, WRAT3, TPT, Category
Test, Raven’s
Colour
Progressive
Matrices, Letter
and Number Series
Tests from
Primary Mental
Abilities Test,
Proverbs Test,
MMPI-2, TAT,
Rorschach, Child
Behavior
Checklist
Phonemic
discrimination,
Wepman’s Test of
Auditory
Discrimination,
non-word
discrimination,
Snowling’s
Repetition
Word reading
tasks
Temple and
Vilarroya
(1990)
Temple,
Jeeves, &
Vilarroya
n=2 (siblings)
Piagetian and postPiagetian tasks
n=3, age 7, 9, & 13
All subjects exhibited deficits on
cognitive tests that suggested
difficulty with inter-hemispheric
transfer of tactile information; other
impairment noted difficulties in
some areas of memory; borderlinelow average FSIQ; children
exhibited drastic split between
Verbal IQ and Performance IQ
Difficulty matching colors presented
to both fields; no difficulty reading
words that crossed the midline;
suggested that anterior commisure
preserves ability to integrate form
but not color
Performance in normal range for
reading and spelling; moderate
deficits on full scale cognitive
measures; no psychopathology
reported on CBCL; MMPI results
indicative of psychological naïveté
and poor self-understanding
Consistent, moderate impairment on
all tasks requiring phonemic
awareness and phonological
processing
Both subjects exhibited impaired
phonological processing which
hindered their ability to read (in a
manner consistent with
developmental dyslexia)
No impairment on perspectivetaking, theory-of-mind tasks
FSIQ in normal range for all
subjects; delayed acquisition of
speech but normal performance at
18
(1989)
Wilson (1983)
n=2, age 3 months
through 4 yrs.
(longitudinal)
Bayley Scales of
Infant
Development,
Third Edition
time of assessment; deficits in
rhyming that may improve with age
Two brothers referred for
developmental delay (~6 months
delayed) were found to have ACC
with no significant dysmorphic
features or syndrome symptoms.
Cites family studies as a good way
to explore the role of genes and
heredity in ACC.
Generally speaking, the more recent case studies focus on highly involved
presentations and/or findings that may contribute to understanding the role of genetics
in disorders of the corpus callosum. Older case studies (e.g., Finlay et al, 2000;
Temple, 1993) tend to provide more in-depth descriptions of 1-3 subjects and
describe their performance on specific tasks. Case studies tend to report significant
outcomes at either end (i.e., impairment or normal functioning), most likely because
the cases were complicated or unusual enough to merit a case study. The majority of
studies highlighted here show children with ACC to have moderate cognitive delays
(Wilson, 1983; Brown & Paul, 2000; Finlay et al., 2000; Panos et al., 2001); however,
a significant portion of the studies report no cognitive impairment. Additional
difficulties reported here include behavioral challenges (Filges et al., 2010), verbal
learning, auditory attention, verbal expression (Panos et al., 2001), interhemispheric
transfer of tactile information, memory (Finlay et al., 2000), phonemic awareness,
and phonological processing (Temple, 1993; Temple et al., 1990).
The results of the case study literature are most dramatically influenced by the
inclusion of subjects with multiple comorbidities and chromosomal disorders, as
children with additional diagnosis or abnormalities consistently exhibit mild to severe
cognitive delay. This observation regarding the case study literature is reinforced by
19
the findings of many descriptive studies. Although case studies are limited in their
generalizability they illustrate the trends in research on ACC over the last forty years
and show the tremendous diversity of children and families who live with ACC.
Quasi-Experimental Studies
Of the 19 quasi-experimental studies initially identified, nine met the criteria for
sample characteristics and research focus, and those are described in Table 3. As
with the case studies, the featured studies were selected because they address
neurocognitive or developmental features of children with ACC as the primary
concern. For this category, the sample composition (e.g., accounting for children
with acquired versus congenital ACC, partial versus complete ACC, etc.) and study
design were also considered when selecting studies.
Table 2: Selected Quasi-Experimental Studies
Author
Symington,
Paul,
Symington,
Ono, &
Warren
(2010)
Turk, Brown,
Symington &
Paul (2010)
Sacco,
Moutard, &
Fagard
(2006)
Brown
(2005)
Sample
n=11
congenital,
complete ACC,
normal
intelligence,
age 15-55 yrs
n=22
congenital,
complete ACC,
normal
intelligence,
aged 8-31 yrs
(mean 15.7 yrs)
n=12 infants (8
total, 4 partial)
congenital ACC
Measures
Happe Theory of Mind
Stories, Adult Faux Pas
Test, Thames Awareness
of Social Inference Test
(TASIT)
Findings
Deficits in the recognition of
emotion, comprehending sarcasm,
and interpreting textual versus
visual social cues
Thematic Apperception
Test; Edinburgh
Handedness Inventory
Deficits in inferring the mental,
emotional, and social functioning
of others; deficits in expressing
those inferences in narrative
format
Qualitative precisiongrasping assessments
n=18 congenital,
complete ACC,
normal
intelligence, age 7-
Formulaic and Novel
Language
Comprehension Test,
Prosody Test
ACC increases likelihood of
delays in bimanual coordination
and bimanual handedness; delay
is greater with complete ACC
Impaired comprehension of literal
and non-literal language and
affective prosody; less
impairment than a similar study
20
Paul,
LanckerSidtis,
Schieffer,
Dietrich, &
Brown
(2003)
Brown,
Thrasher, &
Paul (2001)
Chicoine,
Proteau, &
Lassonde
(2000)
Sauerwein
(1994)
Lassonde
(1988)
13 yrs
n=10
congenital,
complete ACC,
normal intelligence
(presence of
anterior
commisure noted)
n=9
congenital ACC,
normal intelligence
2 partial, 7
complete
(anterior
commisure noted)
n=4 congenital,
complete ACC
Aged 17-31
(included because
age was considered
as a variable)
n=9
congenital
agenesis
n=25 subjects with
collosotomy
n=6 patients with
congenital ACC
aged 13-24
n=4 patients with
colostomy
Formulaic and Novel
Language
Comprehension Test
(FANL-C), Gorham
Proverbs Test, LA
Prosody Test
conducted with adults
Deficits on non-literal items of the
FANL-C
Stroop task
ACC status did not interfere with
interhemispheric Stroop effects
Naming task, manual
task, manual learning
task
Subjects with ACC and children
aged 6-7 years (with intact corpus
callosums) demonstrated similar
patterns of deficit in
interhemispheric transfer
Michigan
Neuropsychological Test,
intelligence tests
Impaired cognitive functioning,
with significant scatter; bimanual
coordination and interhemispheric
transfer of motor tasks were
particularly challenging
Younger children with
collosotomy and children with
congenital ACC demonstrated
accuracy on these tasks,
particularly when compared to
older children who had
commissurotomy
Interhemispheric transfer
of visual and tactile
stimuli
Similar to the case studies, the quasi-experimental studies reveal trends in the
research on ACC. Early research on congenital dysgenesis followed the same line of
investigation as the research on patients who had undergone surgical partitioning or
sectioning of the corpus callosum; they focused on sensorimotor, bimanual
coordination. Researchers demonstrated that children with congenital ACC were
different from children and adults who had surgery (e.g., Lassonde, 1998) but they
struggled to explain those differences (Bogen, 1985; Lassonde, Sauerwein, McCabe
& Laurencelle, 1988; Serrien, 2001). Over time, it has been shown that children with
congenital ACC exhibit some impairment (though less than children and adults with
21
acquired ACC) in bimanual coordination and tactuomotor learning tasks (Chicoine,
Proteau, & Lassonde, 2000; Sauerwein, 1994).
The recent quasi-experimental studies are dominated by research on a subgroup of
people with ACC. Primary ACC is defined by Lynn Paul as "complete absence of the
corpus callosum, with minimal additional neuropathology and general cognitive
functioning in the normal range (i.e., FSIQ>80)" (Paul, Lautzenhiser, Brown, Hart,
Neumann, Spezio, and Adolphs, 2006, pp. 47). These individuals typically function
independently in society, though they exhibit certain social, emotional, and
behavioral deficits. Five of the 9 studies (56%) cited above focus on children and
adolescents with primary ACC, and consequently, normal intelligence. Taken
together, these studies have found that children and adolescents with ACC exhibit
deficits in comprehending sarcasm, certain types of social cues, recognizing emotions
(Symington et al., 2010), comprehending humor and non-literal language (Brown,
2005; Paul et al., 2003), and inferring the emotional and mental states of others
(Symington et al., 2010; Turk et al., 2010). These deficits are often characterized as
higher-order cognitive processes because they require a complex sequence and
synthesis of processing information.
This subset of studies boasts impressive quasi-experimental designs and
methodology; however, just as there are benefits to refining the sample composition
there are also drawbacks. The emphasis on individuals with normal intelligence
restricts the generalizability of these results to the larger population of children with
ACC. Four of the 5 studies consist entirely of subjects with complete ACC, so no
22
conclusions are drawn regarding the impact of partial dysgenesis on cognitive or
developmental features.
Of the featured studies, Brown et al. (2001) and Sacco et al. (2006) are the only
quasi-experimental child studies that utilize a specific group design to allow statistical
comparison of participants with complete ACC with participants who have partial
ACC. These two studies are too different in purpose and design to synthesize their
results. Specifically, the Brown et al. study examined performance of adolescents on
a very specific task, whereas the Sacco et al. study assessed the emergence of a set of
developmental milestones in infants. Together, these studies illustrate a common
theme that emerged throughout the literature review: within a subgroup of children
and adolescents with ACC (i.e., primary ACC), the degree or type of dysgenesis does
not significantly or consistently affect performance on specific tasks (Brown et al.,
2001); however, overall development of children with ACC (inclusive of all cognitive
levels) is likely improved by the presence of a portion of the corpus callosum (i.e.,
partial ACC). This must be regarded as a tentative generalization, since so few
studies have explicitly compared performance of individuals with partial versus
complete ACC in experimental settings.
Descriptive Studies
Table 4 summarizes the 20 descriptive studies that met our criteria for selected
review. This category is comprised largely of retrospective, population-based, and
epidemiological studies (i.e., descriptive studies). These studies provide the most
unbiased information about incidence and prevalence of ACC, as well as potential
23
environmental factors. These studies also provide some of the only longitudinal data
on children with ACC, even though much of these data come from retrospective chart
reviews. Retrospective studies have numerous limitations; researchers have little or
no contact with subjects, there is very little control over the measures used, and
conditions in which data are gathered is non-standardized and sometimes even
unknown. Still, these types of studies constitute an important component in the early
investigations of all medical conditions and, as we will see, they do the same for
ACC.
Table 3: Selected Descriptive Studies
Study
Cignini et al.
(2010)
Sample Size
n=13, congenital,
complete ACC
Measures
Stanford-Binet
Findings
Typical psycho-motor and cognitive
development in 92.3% of sample
Tang et al.,
(2009)
n=29
MRI, unspecified
neurological and
developmental
assessments
Additional abnormalities were
discovered in 26 of the cases and all
had poor neurodevelopmental
outcomes; outcomes were good for all
cases with isolated ACC
Chadie et al.
(2008)
n=20
Brunet-Lezine,
Wechsler Preschool and
Primer Scale of
Intelligence Revised,
Wechsler Intelligence
Scale for Children-III,
Terman-Merril scale
Normal development observed in 55%
of sample; Moderate (SLD) in 25%;
Severe (IQ<70 or CP) in 20%
Glass, Shaw,
Ma, & Sherr
(2008)
n=472
Record Review
Fratelli et al.
(2007)
n=7
Questionnaire
Environmental risk factors associated
with ACC are advanced maternal age
and premature birth; no distinction
between partial and complete
3 developmentally normal
3 moderate DD
1 severe DD
Badaruddin et
al. (2007)
n=61
Caregiver survey, Child
Behavior Checklist
(CBCL)
24
Children with ACC experience
problems with sleep, attention, social
function, thought, and somatic
Bedeschi et al.
(2006)
Francesco et
al. (2006)
Genetic, clinical, and
lab testing
Griffiths Scale,
Wechsler Primary and
Preschool Scale of
Intelligence, Wechsler
Intelligence Scale for
Children
Neurological
examination
Ramelli et al.
(2006)
n=6
Sztriha, L.
(2005)
n=16, 8 with
ACC as primary
feature
n=189
MRI
Ng et al.
(2004)
Moutard et al.
(2003)
n=7
MRI, feeding and
swallowing evaluations
Neuropsychological
evaluation
dos Santos et
al. (2002)
n=20, 18 with
complete ACC, 2
with hypoplasia
Neurologic evaluation,
neuroimaging study,
cytogenetic analysis
Shevell (2002)
n=24
Standard developmental
assessments
Goodyear
(2001)
n=75 (14 dx
prenatally, 61 dx
postnatally)
Bennet et al.
(1996)
Vergani et al.
(1994)
Pilu (1993)
n=15
developmental
milestones, by
pediatrician,
neurosurgeon or parent
report
MRI, karyotyping
Byrd et al.
(1990)
n=105 (n=26 for
isolated ACC)
Doherty et al.
(2005)
n=63, 30 with
complete ACC,
33 with partial
n=9, 6 with
isolated ACC, 3
with associated
malformations
n=17
n=14
Caregiver survey
Ultrasound, clinical
exam
n=35
MRI, CT, and US
25
complaints; children with ACC were
less impaired than a comparison cohort
of children with autism
Neuromotor impairment in 58/63 cases;
9/63 (14%) had normal IQ; no unique
prognosis for ACC
Development was normal for 6/6
(100%) of children with isolated ACC
Neurological examination was normal
for 6/6 (100%) of children; 1 child had
nystagmus
Normal or borderline development was
observed in 4/6 (67%) children with
primary ACC (2 were lost to follow up)
Children with ACC experience altered
pain perception, sensory deficits,
altered patterns of feeding/eating,
elimination, and sleep
Normal or mild developmental delay
observed in 2/7 (28%) of children
FSIQ in the normal range for 81% of
sample; no difference between partial
and complete ACC group
Psychomotor retardation observed in
13/20 (65%); proportion of those who
had complete ACC vs. hypoplasia not
specified
Developmental delay observed in
83.3% of sample; 3 mild w/MR, 8
w/moderate MR, 9 w/severe MR
Developmental delay observed in
72.5%; 39.1% diagnosed with mental
retardation
Normal development observed in 6/16
(40%)
Normal development reported for 5/14
(36%) children
Prognosis is uncertain but probable to
be borderline or normal if agenesis is
isolated
Categorizes agenesis and commonly
associated malformations (e.g.,DandyWalker, migrational disorders, etc.); 18
of 26 subjects had normal neurological
outcomes
A number of the descriptive studies cited in Table 4 examine development in
prenatally diagnosed ACC by following children diagnosed in utero and conducting
(or reviewing) assessments in longitudinal follow-up. These studies employ diverse
measures and generally report broad categorizations of cognitive or developmental
functioning, which makes them difficult to use for an aggregated analysis. Still, they
provide valuable information about the overall functioning of relatively substantial
samples of children with congenital ACC.
The general report from retrospective and prospective studies of infants and
children with isolated ACC is optimistic. Most of the studies report that a majority of
the sample exhibits normal or mildly impaired development. Cognitive and
developmental functioning are likely to be within the normal range if the ACC is the
only abnormality present. Developmental delays are commonly reported in the
following areas: speech, motor, and social abilities. As Chadie et al. (2008) point out,
many of those delays are responsive to early interventions, again, particularly if the
agenesis is isolated. Other descriptive studies (i.e., Doherty et al., 2005 and
Badarduddin et al., 2007) suggest that children with ACC experience social and
developmental delays, but to a lesser extent than children with other disabilities (i.e.,
autism).
Review Papers
Two review papers met our criteria for selected review, and they are highlighted
in Table 4 along with two other studies. The additional studies are included to
illustrate the entirety of the review literature on children with congenital ACC. The
26
results for the review papers were dramatically reduced when the criteria for child
studies was applied (initial results returned 23 reviews).
Table 4: Selected Review Papers
Author
de Campos et
al. (2009)
Hannay et al.
(2009)
Penny (2006)
Gupta &
Lilford (1995)
Purpose
Analyzes publications from 1980 to
2008 regarding reaching and grasping
movements in infants. Attention to
methodological procedures used in the
studies under review
Review of magnetic resonance imaging
(MRI) data of the CC in 193 children
with spina bifida meningomyelocele
Review of neonatal sonographic
detection of ACC
Literature review to assist with
prognosis for fetally diagnosed ACC
Findings
Prematurity, cerebral palsy, Down
syndrome, intrauterine cocaine exposure
and agenesis of corpus callosum were
determined to be risk factors for delays in
reaching and grasping.
Partial agenesis was observed in 102
children and within 15 CC regional
patterns.
Focus on diagnosis, etiology, and the role
of medical technology in determining
presence/absence of CC.
Isolated ACC indicates a very good
prognosis (85% chance of normal
development); fetal karyotyping is
recommended since outcomes are poor
when the ACC is associated with other
abnormalities
The primary purposes of the paper by Hannay and colleagues (Hannay, Dennis,
Kramer, Blaser, & Fletcher, 2009) were to pay tribute to Arthur Benton and to
examine callosal development in a sample of children with spina bifida
meningomyelocele. The review by de Campos et al. (2009) looked at publications
the development of reaching and grasping in infants with ACC as compared to
typically developing infants. Reaching and grasping represent significant
developmental milestones for infants, so delays in this area are potentially predictive
of later difficulties. Consequently, the methodology and conclusions of that research
are relevant to the present paper. Penny's 2006 review of neonatal sonographic
detection discusses the etiology and presentation of ACC, but its real focus is on the
role of technology (ultrasound, prenatal MRI, etc.) in prenatal diagnosis of agenesis.
27
As with the paper by de Campos et al., Penny's study has important implications for
our investigation, but it pursues a different aspect of ACC than the current paper (i.e.,
technology and diagnosis rather than developmental features). The most apparent
contrast between the current paper and previous reviews is the emphasis on children;
only one other review focuses on children with congenital ACC (Gupta & Lilford).
The aims of that study were to quantify the likelihood of typical development for
children with ACC. The current paper will incorporate this information into a
comprehensive portrait of the existing research on ACC, with particular attention to
methodology and the implications that methodology can have for synthesizing
information and translating research into practice.
The overall findings in the review papers mentioned here are consistent with
reports from the other types of studies. Children with other developmental
disabilities present an increased risk for ACC, though ACC is not a cause or a direct
result of the associated abnormality. Most importantly, children with isolated ACC
are likely to experience typical development (Gupta & Lilford, 1995).
There are a few review papers that do not focus on children, but which are worth
mentioning because they focus on agenesis of the corpus callosum. In 2011, Lynn
Paul published a comprehensive discussion of callosal development, and the
developmental disabilities associated with callosal absence and malformation. The
article lays a foundation for linking clinical presentations with the structural presence,
absence, or malformation of the corpus callosum. Paul published another paper in
2007. That paper focused on the etiology, characteristics, and implications for
neuroimaging research related to ACC. Paul and many others at the Travis Research
28
Institute have made substantial contributions to the research on ACC (5 of the initial
19 quasi-experimental studies on ACC have been led by her).
Additional Findings
Although the initial focus of this paper was on cognitive features of children with
ACC, many interesting studies were discovered to provide important information
about how children with ACC develop and function in their daily lives. In the interest
of maximizing the utility of the ICF-CY, some of those findings will be reviewed
here and incorporated into the application of the ICF-CY.
Goyal et al. (2010) examined the ophthalmological characteristics of a sample of
nineteen children with partial agenesis (nonsyndromatic). The significant
neurological features present in the sample were global developmental delay (62%)
and epilepsy (46%). The majority of children in the sample had ocular defects.
Specific deficits included poor visual acuity, refractive errors, and strabismus.
Doherty et al. (2006) also reported vision difficulties for many children with ACC,
including difficulties with depth perception, muscle control, nystagmus, and
strabismus (>10% of the sample).
The literature consistently reports that children with ACC exhibit delays in
bimanual motor development (Sauerwein, 1981; Sacco, 2006; Mueller, 2009). An
investigation of visuomotor learning, where subjects responded motorically to visual
stimuli, revealed significant deficits in the performance of the group with ACC on
transference of learned visuomotor tasks (Chicoine, A., Proteau, L., & Lassonde, M,
2000). An interesting facet of the Chicoine et al. (2000) study was the inclusion of a
29
cohort of 6- and 7 year-olds with typical callosal development. The authors reported
that the difficulties experienced by the ACC cohort were similar to the performance
of the 6- and 7-year-olds, which may suggest that interhemispheric transfer of
unilateral visuomotor learning requires full mylenation of the callosal structures (and
consequently, is not realized until adulthood), perhaps indicating lifelong deficits for
the individuals with ACC.
Additionally, children with ACC are likely to experience feeding problems.
Doherty et al. (1995) found that caregiver reports of feeding problems were
statistically significant when compared to a control group consisting of siblings
without ACC. Ng, McCarthy, Tarby, and Bodensteiner (2004) evaluated seven
children with ACC and found that all of them exhibited oral-motor weakness and
sensory defensiveness, which may reveal an underlying cause of the reported feeding
difficulties.
Moes, Schilmoeller, & Schilmoeller, 2009 found that children with ACC were
toilet trained later than their siblings, and that night-time enuresis was a significant
problem among the respondent sample. Finally, children with ACC are reported to
experience difficulties with sleep (Kuks, Vos, & O'Brien, 1987; Badaruddin et al.,
2007) and decreased pain perception (Doherty et al., 2005).
Alignment of Reviewed Features with the ICF-CY
The second objective of this paper was to apply the ICF-CY framework to the
findings on ACC, in order to summarize the results and illustrate how this framework
can be used to guide research, clinical, and community approaches to children with
30
ACC. Tables 5 through 7 illustrate how the application of the ICF-CY can be used to
describe what we currently know about the functional abilities or limitations of
children with ACC. There are four broad categories of classification: Body
Functions, Body Structures, Activities and Participation, and Environmental Factors.
These represent the first level of reporting, and they are represented by alpha codingb for Body Functions, s for Body Structures, d for Activities and Participation, and e
for Environmental Factors. Since it would be impossible to summarize the
environmental factors experienced by the subjects in the studies reviewed here, the
fourth category (Environmental Factors) will not be included below.
The ICF-CY was designed as a comprehensive catalogue of functioning, so the
next level of reporting is a numeric code that corresponds to a specific body function,
body structure, activity or type of participation, and environmental factor. The final
level of reporting represents the degree of impairment, using a scale of 0 (no
impairment) to 4 (complete impairment or limitation). When the degree of ability or
limitation is not yet specified, a code of 8 is assigned. Typically, this code would be a
fixed number at each point of evaluation; it can reflect change (improvement or loss
of functioning) over time when two codes for one person's functioning are compared
over time. Since the tables below illustrate the range of functioning that has been
observed across all of the studies reviewed here, this information is reported as a
range based on the highest and lowest levels of functioning reported across the
studies. Aspects of functioning that have not been explicitly studied, but which are
strong candidate-topics for future research, are designated as 8 (i.e., not specified).
31
Table 5: ICF-CY Body Functions Indicated in ACC Research
Coding
Chapter 1 Mental Functions
b117.1-3
BODY FUNCTIONS
Function
Intellectual functions
b122.1-2
Global Psychosocial functions
b125.1-2
b134.1-2
Dispositions and intra-personal
function
Sleep functions
b140.1-2
Attention functions
b144.0
Memory functions
b147.1-2
Psychomotor functions
b152.1-2
b163.1-3
b164.1-3
Emotional functions
Basic cognitive functions
Higher-level cognitive functions
Illustrative Studies
Tang et al., 2009; Goodyear et al.,
2001
Badaruddin et al., 2007; Turk et
al., 2010
Badaruddin et al., 2007
Kuks et al., 1987; Badaruddin et
al., 2007
Dell'Acqua et al., 2005;
Sauerwein & Lassonde, 1994
Sauerwein & Lassonde, 1994
(relative strength)
dos Santos et al., 2002; Bedeschi
et al., 2006; Moes et al, 2009
Symington et al., 2010
Tang et al., 2009; Sztriha, 2005
Huber-Okraine et al., 2005;
Brown et al., 2005
Chapter 2 Sensory Functions and Pain
b210.1
Seeing functions
Goyal et al., 2010
b215.1
Functions of structure adjoining
Goyal et al., 2010
the eye
b260.1
Proprioceptive function
Moes et al., 2009
b279.1
Additional sensory functions,
Doherty et al., 2005
other specified and unspecified
b280.1-2
Sensation of pain
Moes et al., 2009; Doherty, 2005
Chapter 3 Voice and
Speech Functions
b399.1-2
Voice and speech functions,
Chadie et al., 2008
unspecified
Chapter 5 Functions of the Digestive, Metabolic, and Endocrine Systems
b510.1-2
Ingestion functions
Ng et al., 2004
b525.1
Defecation functions
Moes et al., 2009
Chapter 6 Genitourinary and Reproductive functions
b610.1-2
Urinary excretory functions
Moes et al., 2009
Table 6: ICF-CY Body Structures Indicated in ACC Research
BODY STRUCTURES
Coding
Function
Chapter 1 Structures of the Nervous System
s110.4
Structure of the brain
Chapter 2 The Eye, Ear, and Related Structures
s220.1
Structure of the eyeball
s299.1-2
Eye, ear, and related structures,
32
Illustrative Studies
All, defining feature
Doherty et al., 2005
dos Santos, 2002
unspecified
Chapter 7 Structures Related to Movement
s710.1
Structure of head and neck region
Moes et al., 2009; Doherty et al.,
2005
Table 7: ICF-CY Activities and Participation Indicated in ACC Research
ACTIVITIES AND PARTICIPATION
Coding
Function
Illustrative Studies
Chapter 1 Learning and Applying Knowledge
d133.1-2
Acquiring language
Ng et al, 2004
d159.8
Basic learning, other specified
and unspecified
d160.1
Focusing attention
Badaruddin et al., 2007
d161.1
Directing attention
Hines et al., 2002
d166.1-3
Reading
Temple, 1990
Chapter 2 General Tasks and Demands
d230.8
Carrying out daily routine
Chapter 3 Communication
d310.1-2
Communicating with- receivingPaul et al, 2003; Turk et al, 2009
spoken messages
d315.1-2
Communicating with- receivingPaul et al, 2003; Turk et al, 2009
nonverbal messages
Chapter 5 Self-Care
d530.1
Toileting
Doherty et al., 2005
d550.1
Eating
Ng et al., 2004
d560.1
Drinking
Ng et al., 2004
Chapter 6 Domestic Life
d699.8
Domestic life, unspecified
Chapter 7 Interpersonal Interactions and Relationships
d720.8
Complex interpersonal
interactions
d729.8
General interpersonal
interactions, other specified and
unspecified
d770.8
Intimate relationships
Chapter 8 Major Life Areas
d839.1-3
Education, other specified and
unspecified
33
CHAPTER 4
DISCUSSION
Cognitive and Developmental Features of Children with Congenital ACC
This paper set out to accomplish two objectives. First, we sought to describe the
literature on ACC and synthesize the findings on cognitive and developmental
features of that population. In the initial search described above 273 studies were
identified. One twenty six of those studies met our criteria for child studies (i.e.,
~46%). In the second stage of review, studies were classified as clinical case studies,
quasi-experimental studies, descriptive studies, and review papers (results reported in
Figure 4). The most significant thing to note here is that of the 273 studies that
discuss agenesis or dysgenesis of the corpus callosum, only 9 examine cognitive or
developmental features of children with congenital ACC using a quasi-experimental
design. Of the 19 studies initially selected, the sample sizes range from n=1 to n=24,
with a mean sample size of 7.5 (excluding controls). Three of those studies focus on
complete ACC, two include participants with partial ACC, and four did not provide
details regarding the degree of dysgenesis. If we are to produce reliable conclusions
about cognitive profiles and developmental trajectories, let alone target interventions
to support children and families, this category needs to increase exponentially.
Although much work needs to be done to support more actionable conclusions,
the existing research provides an initial picture of neurodevelopmental functioning for
children with ACC. At least one quasi-experimental study suggests that children with
congenital ACC exhibit a relative strength for receptive vocabulary (Sauerwein &
Lassonde, 1994). The same study reinforced the finding that individuals with ACC
demonstrate a specific ear advantage for verbal stimuli, meaning that stimuli
presented to one or both ears are consistently recognized with more accuracy from
one ear. This may contribute to superior performance in dichotic listening tasks, and
suggests the presence of different auditory perceptual capabilities.
Visual processing in ACC has primarily been studied as a way of determining
deficits in interhemispheric transfer of information. Children with ACC consistently
struggle with bilateral presentation of information (Sauerwein & Lassonde, 1983).
This has been found with even greater frequency in adults with ACC (Brown et al.,
1999). Children with ACC may also experience more redundancy gain (i.e.,
decreased reaction time when multiple stimuli are presented) than expected if
presented with visual stimuli that sharply contrasts with the background in color or
brightness (Corballis, 1998).
With regard to attention, Sauerwein and Lassonde (1994) did not observe any
deficits in the attentional capacities of children with ACC. When compared to their
classmates from a special education classroom, the children with ACC performed as
well as their peers on tasks that may reflect some aspects of attention (e.g., digit
span). In contrast to these findings, a descriptive study conducted by Badaruddin et
al. (2007) found that caregivers of children with ACC (aged 6-11 yrs) reported
clinically significant problems with attention. One potential explanation for the
conflicting report may relate to the methodology of determining attention problems.
35
In the quasi-experimental studies, select groups of children were evaluated on specific
tasks, primarily response time to visual or auditory stimuli. In the Badaruddin study,
caregivers were reporting on their daily behavioral observations of their children.
The category of attention problems on the caregiver report form is a much broader
category than the functions assessed in the quasi-experimental designs because it gets
at the DSM-IV symtomotology for ADHD, rather than performance on a given task.
An additional consideration comes from adult studies, which suggest that ACC
manifests the greatest impairment in the areas of social and emotional
communication. Attention problems may be more likely to be observed in daily
routines than in isolated, cognitive tasks (Paul, Schieffer, & Brown, 2004; Paul,
Lautzenhiser, Brown, Hart, Neumann, Spezio, & Adolphs, 2006).
One challenge in reviewing reports of cognitive ability in children with ACC is
that many studies use IQ scores as a cut score for inclusionary criteria, but few studies
provide the cognitive profile information that is needed to draw a clear picture of
individual functioning. Composite scores, subtest scores, qualitative information, and
other details regarding administration techniques would dramatically enhance the
utility of this literature. In addition to assessment information, another challenge to
drawing conclusions about this realm of functioning is the inconsistency of broad
classifications, such as developmental delay. For example, Doherty et al. (1995)
reported that 80.7% of people with ACC had a diagnosis of Developmental Delay
(DD), compared to 2.1% of non-ACC siblings (which were included as a reference
group). That is valuable information given the nascent state of neurocognitive
36
research on ACC, but it provides relatively little information about how children with
ACC are functioning in daily life.
Application and Implications of the ICF-CY for Research and Clinical Practice
In hopes of contributing something unique to the research on children with ACC,
the second goal of this paper was to apply a globally accepted classification system to
the findings presented above. The ICF-CY is a tool that is increasingly used in
clinical settings in Europe, and which has been endorsed by practitioners of all types
from around the globe. It is most relevant to our purposes because it provides an
efficient way of describing what we know about the range of functioning exhibited by
children with ACC. Tables 5 through 7 summarize the findings of the 145 studies
reviewed for this paper in three pages, and they do so in a specific and personoriented (as opposed to label-oriented) way. This method of describing children with
ACC would be useful for clinicians, caregivers, and teachers who seek to monitor
development and design therapeutic intervention. This approach has utility for
researchers as well as clinicians, as many of the functions listed translate smoothly
into measurable tasks for a quasi-experimental research design.
Limitations
The current paper emphasizes cognitive and developmental features of children
with ACC. As a result, a number of high-quality studies on functional mapping and
typical callosal development have not been included. The research on typical callosal
development has remained surprisingly separate from research on congenital
37
agenesis. This is likely because ACC so often occurs with complex comorbidities
that would confound a study devote to callosal functioning. Although the challenges
of incorporating children with ACC into research on brain imaging and callosal
development are substantial, the potential benefit to research and clinical practice are
significant.
Directions for Future Research
In 1972 Ettlinger wrote "Despite a few positive findings...most striking is the lack
of deficit in the patients with total agenesis. These finding are perhaps most readily
understood by supposing that these patients use non-callosal commissural pathways
which have certain functional limitations. Further study of these patients seems
justified, with particular reference to their highly specific impairments." (page 345).
The excitement surrounding the early observations that clear differences exist
between patients with acquired ACC and those with congenital ACC should be
magnified in the current research environment. The rigorous study of ACC holds the
potential for insight into the most intriguing topics in neuropsychology and
neuroanatomy today- plasticity, resiliency, structural/neuroanatomical development,
functional mapping, and interhemispheric connectivity.
We have known about congenital malformations of the corpus callosum since
Reil identified ACC in 1812 ((Slager, Kelly & Wagner, 1957). We have known that
different malformations can manifest drastically different outcomes since the 1960s.
What we have not succeeded in doing is linking the functional outcomes to the
anatomy of the corpus callosum. Recent research is moving in the right direction. A
38
paper published by Luders, Thompson, & Toga (2010) mapped callosal development
in 190 healthy children and adolescents. Lynne Paul's most recent review paper
(Paul, 2011) presents an initial survey of the portions of the corpus callosum that are
related to specific developmental disorders. In both of these examples, the
experimental design is focusing on the brain as the independent variable which gets to
the heart of the questions that have been asked by researchers investigating disorders
of the corpus callosum for decades.
As brain-based research on ACC moves forward, capitalizing on technology and
increasingly rigorous quasi-experimental designs, the implications for translational
research are increasingly important. The emphasis throughout this paper on
examining functional characteristics of children with ACC represents the essential
link between research and practice as the research on ACC evolves. The studies
reviewed in this paper reveal many functional deficits that should be further examined
and considered in the context of early intervention and support services. For
example, motor delays such as the emergence of bimanual coordination (Sacco et al.,
2006) is an ideal target for early occupational and physical therapy interventions
(Chadie et al, 2008); feeding and swallowing difficulties are typically overcome or
ameliorated by early therapy from qualified speech therapists (Ng et al., 2004);
medical and behavioral interventions can be important for children and caregivers
that experience difficulty with toilet training.
In describing the research on cognitive and developmental features of children
with ACC, it is hoped that this review has elucidated the opportunities and
importance of future research on this topic. Descriptive studies will bolster the
39
information about incidence within and outside of the population with developmental
disabilities, environmental factors, and behavioral and adaptive functioning. Quasiexperimental studies that focus on rigorous evaluation of neurocognitive functioning
will dramatically enhance our understanding of developmental trajectories for
children with ACC. Case study applications of tools like the ICF-CY will refine
diagnostic approaches and interventions for children with ACC. Finally, the
incorporation of advanced imaging techniques with an emphasis on the brain as the
independent variable will contribute not only to our understanding of ACC, but also
to our understanding of the most salient topics in neuroanatomy and neurophysiology
today.
40
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