Have you ever wondered if [x, y, z] is typical of a child with a disorder of the corpus callosum?
We’re hoping to answer these questions!
The DCC Lifespan Studies are a part of a research program from California Institute of Technology and University of Minnesota, studying the development of infants and children with disorders of the corpus callosum (DCC). We are seeking better ways to help children with DCC grow to their full potential by studying mental and behavioral development in infants and children with DCC. Over the last 10 years, we have collected data from over 500 individuals with a DCC and have published research on a range of aspects of development.
This is both a longitudinal and cross-sectional study, meaning that we track individuals of ages 6 months – 17 years over multiple years. This helps to highlight differences both within and between individuals, leading to a more nuanced overview of typicality.
(Click here to learn about adaptive functioning in infants with ACC!)
(Or here to learn about social and communication skills in infants with ACC!)
We are now beginning to utilize the plethora of “background” information, such as diagnosis information, medical history, developmental history, and more, in this natural history study. Natural history studies are a type of study that investigate the progression of a disorder over time. This is done by using anecdotal information from our participants to get a better idea of what is “typical” of DCC.
Our study includes information about:
- Callosal disorder diagnosis
- Corpus callosum diagnosis (pre- or postnatal)
- Diagnosis methods (scan type/age)
- Diagnosis over time (medical updates)
- Medical history
- Physical health (vision, hearing, cardiac, seizures, medications)
- Psychological health (ASD diagnosis, psychiatric diagnoses)
- Family background
- Family medical history (history of DCC or ASD)
- Demographic information (race, ethnicity, education, income)
- Pregnancy & birth history
- Conception
- Pregnancy complications (illness, physical trauma, medications, substance use)
- Delivery complications (breathing, infections, hospital stays)
- Development history
- Age of first word and steps
- Performance in school, social skills, sleep, feeding issues
Participants
Of our study’s 807 enrollees, 493 have fully completed the background survey, 75 have partially completed the background survey, and 239 have not submitted any information.
Of our 493 participants with a full background, 56.8% are male (43.2% female).
87.6% identify as Not Latino/Hispanic (9.9% Latino/Hispanic, 2.4% did not answer).
78.9% identify as Caucasian/White, 20.1% identify as multiracial, 3.5% identify as Asian, 3.5% identify as other, 1% identify as black/African-American, 0.4% identify as American Indian, and 0.2% identify as Pacific-Islander/Hawaiian, and 2.4% did not answer.
69.2% of our sample live in the United States, with the next highest populations being from Great Britain (9.1%), Australia (5.3%), and Canada (4.3%).
Healthcare access varies by country, specifically in the ability to have brain imaging and early intervention. These are two aspects of participant variability that could affect our participants and thus, our results.
Corpus Callosum Diagnosis
Corpus callosum malformations can be described by the umbrella term of dysgenesis of the corpus callosum, meaning that the corpus callosum didn’t develop typically. Under this term, there are two distinctions: agenesis of the corpus callosum (didn’t develop at all / absent) and hypoplasia of the corpus callosum (full length but thin). With a diagnosis of agenesis of the corpus callosum, it is categorized by whether it is complete or partial (CACC or PACC).
There are often additional neuropathologies seen within individuals with a disorder of the corpus callosum (DCC). In our study, we group them by whether they are commonly associated with DCCs. If they are associated with DCC, they are categorized as “common” neuropathologies. If they are not associated with DCC or they can lead to more severe effects on development, they are categorized as “atypical” neuropathologies.
Common neuropathologies include: colpocephaly/ventriculomegaly, interhemispheric cyst, ‘hydrocephalus’, absence of septum pellucidum, interhemispheric lipoma.
Atypical neuropathologies include: heterotopia, microcephaly, abnormal pituitary, cerebellar dysplasia, genetic abnormalities, cerebrovascular incidents, seizures.
Table 1. Callosal disorder and group. Our sample of 493 participants is broken down by callosal disorder diagnosis and additional pathology grouping.
Brain Imaging
The structure of the brain changes very little after age 2. Additionally, children under age 2 may have a harder time staying still for a brain scan. For these reasons, it is ideal for individuals to have brain imaging done at 2 years or later. As researchers, it helps us to categorize our participants accurately, which makes our research more accurate. We can more confidently analyze differences between different callosal disorder diagnoses (e.g., Is this symptom more prevalent in individuals with complete agenesis or hypoplasia?). It is also important to have an accurate brain scan for personal records! If an individual has an injury or accident, it is helpful to have a baseline comparison of structural abnormalities in the brain.
To fully enroll in our studies, we ask participants to submit records as proof of diagnosis. Ideally, we would receive images from every participant. We work with neuroradiologists at UCSF that are experts in identifying disorders of the corpus callosum, and they confirm our diagnosis from participant scan images. This provides a confirmed, accurate diagnosis, as other radiologists may be less familiar with disorders of the corpus callosum. Additionally, this provides consistency in diagnosis, as the same team is reviewing all records. However, we understand that accessing medical information can be difficult, so we accept MRI/CT scan reports, as they provide a diagnosis and other noted abnormalities.
In our study, the majority of our participants enroll before 2 years, so it is difficult to obtain scans over the age of 2 years. Additionally, 62.7% of our participants are diagnosed prenatally, meaning that their first diagnosis was from an ultrasound or fetal MRI. These diagnoses are not ideal, as babies are prone to move and there is blurring of the white and grey matter. Both of these obstacles lead to a higher likelihood of inaccurate callosal diagnosis categorization. So, for portions of this study that rely on subgroup distinction, we are using a smaller sample size made of individuals with a postnatal (after birth) record submitted to us. This reduces our sample size by nearly half, leaving the verified sample with 256 participants.
Table 2. Callosal disorder and group. Our verified sample of 256 participants is broken down by callosal disorder diagnosis and additional pathology grouping.
Figure 1. Incidence rate of common neuropathologies in the verified sample of 256 participants.
Figure 2. Incidence rate of atypical neuropathologies in the verified sample of 256 participants.
Takeaways
Natural history studies are the foundation of building research for rare and developmental disorders. With this specific study, we will establish a baseline of typicality in DCC development. We are using the lived experience of our participants to inform future individuals, families and medical providers with evidence of what development looks like in DCCs.
A majority of our participants are diagnosed before 12 months, so our sample is representative of individuals who were diagnosed early. In the future, we hope this will inspire similar research in adult populations, specifically adults who were diagnosed later in life. Additionally, our sample has Complete ACC with common or no additional neuropathologies, and this is what our findings represent.
For findings to represent all individuals with a DCC, research participation has to include all! We invite individuals of all ability and developmental levels, as many times as possible, with as much detail as possible.
Upcoming Fellowship Activities:
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- Webinars:
- Supporting Development: Intervention and Treatment in the Early Years
- Webinars:
- May 19th, 8pm ET
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- Emergence of ASD and Other Diagnoses in Later Childhood
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- June 16th, 8pm ET
- Interactive Community Report
- Coming in early July!
- Published Research Paper
Presenters: Ella Bohlman, B.S. and Lynn K. Paul, Ph.D.
“Have you ever wondered ….?”
Why don’t doctors know anything about this diagnosis?!
Is this ‘normal’ for a child with DCC? When should we get another MRI?
When should we go back to the neurologist? Should we get genetic testing?
Why aren’t people with DCC more similar? Does DCC really matter?
Was participating in that research study a waste of time?
What can I do to help my child succeed?
Learn how NODCC is working with scientists to answer these questions.
Lynn K. Paul will give an update about the status of DCC research in the United States. Ella Bohlman will present a portion of her findings from the Natural History fellowship supported by NODCC.