Our Mission: To improve the health & quality of life for those with CDD
publication summaries for families
research publications
Content Validation of Clinician-Reported Items for a Severity Measure for CDKL5 Deficiency Disorder
Saldaris J, Weisenberg J, Pestana-Knight E, Marsh E, Bernhard S, Rajaraman R, Heidary G, Olson HE, Devinsky O, Price D, Jacoby P, Leonard H, Benke TA, Demarest S*, Downs J* (2021) Content validation of clinician-reported items for a severity measure for CDKL5 Deficiency Disorder. Journal of Child Neurology, 36(11), 998-1006. DOI: 10.1177/08830738211019576.
https://pubmed.ncbi.nlm.nih.gov/34378447/
Background
Research is currently underway to develop new medicines for CDKL5 deficiency disorder (CDD), including gene therapies. To test these medicines, we also need outcome measures that can identify whether the new medicines have worked.
Our team is working on a program of research funded by the NIH which will develop and test measures for CDD to capture the different areas that are important to families. This aimed to develop an assessment of clinical severity, the CKDL5 Clinical Severity Assessment - Clinician reported (CCSA-Clinician). This study assesses the content validity, that is whether the items and responses were clear, relevant and comprehensive.
What we did
Previously, Professor Tim Benke and team developed an assessment of severity based on the opinions of clinicians and researchers of what should be included in the measure.
In the current study, we refined the initial clinical assessment along with clinicians from the CDKL5 Centres of Excellence (COE) in the US. We interviewed each clinician individually to make sure the items were relevant to their patients, and clear and easy to understand. We then held two meetings to come to a consensus on the final items and their responses.
What we found
The original CCSA-Clinician included 26 items. After reviewing all interview data, 11 items were added, 8 items removed, and 18 items were revised. Therefore, the revised CCSA-Clinician comprised 29 items.
The items described:
1. Functional abilities (gross motor and hand function, communication, vision and attention).
2. Neurological impairments (eye alignment and movement, muscle tone, dystonia, dyskinesias, stereotypies, autonomic function and behaviours).
The CCSA-Clinician also considers how the child is feeling on the day and possible influencing factors (e.g., time since the last seizure, current medications) as these could impact the child’s abilities on a given day.
Why this is important
This initial validation of the CCSA-Clinician is an essential first step in developing the measure towards clinical trial readiness and is important information for the US Food and Drug Administration (FDA). We developed the CCSA-Clinician through interview and consensus methods to fine tune the measure for children with CDD.
The development, content and response process validation of a caregiver-reported severity measure for CDKL5 deficiency disorder
Ziniel SI, Mackie A, Saldaris J, Leonard H, Peter Jacoby P, Marsh ED, Bernhard Suter B, Pestana-Knight E, Olson HE, Price D, Weisenberg J, Rajaraman R, VanderVeen G, Benke TA, Downs J*, Scott Demarest* (2023) The development, content and response process validation of a caregiver-reported severity measure for CDKL5 deficiency disorder. Epilepsy Research, 197: 107231. DOI :10.1016/j.eplepsyres.2023.107231.
https://pubmed.ncbi.nlm.nih.gov/37751639/
Background
Children with CDD often have seizures that are hard to control, along with challenges in their development, communication, and functioning in daily life. Because their needs are so complex, it is difficult to find measures that can track small but important changes in symptoms or progress—especially from the perspective of caregivers who know them best. This study set out to develop a measure that parents and caregivers can use to report their child’s symptoms.
What we did
Previously, Professor Tim Benke and team developed first draft of questions for parents to report severity of symptoms, based on the opinions of clinicians and researchers on an international expert panel of what should be included in the measure.
For this study, we worked closely with parents of children with CDD to modify the measure to best track severity of symptoms and development. This included:
1. Three rounds of interviews with 15 parents, we asked them to “think out loud” as they answered the questions, so we could understand what made sense, what felt confusing, and what was most relevant to their child’s experience.
2. Testing the updated version with parents to make sure it worked well and could be used for children who have a wide range of abilities.
What we found
Based on the feedback of parents, we created two sections to the parent reported measure:
· Caregiver Clinical Severity Assessment- This section looks at the medical symptoms (e.g., seizures, vision issues, sleep, and behaviour) observed over the last month.
· Caregiver Developmental Assessment- This section focuses on the child’s developmental skills (e.g., gross and fine motor, communication) observed over the last month.
After modifications, parents said the new measures were suitable for their child, were clear, and the questions were relevant to their child’s experience.
Why this is important
These new assessments will help families and doctors better understand how children with CDD are doing over time. They will also be useful in future research and clinical trials to show whether a treatment is making a difference. Because this measure was shaped by families, it reflects what truly matters to them. This is an important step toward giving families a stronger voice in care and research, helping more children with CDD get the support they need.
Psychometric evaluation of clinician- and caregiver-reported clinical severity assessments for individuals with CDKL5 deficiency disorder
Saldaris JM, Jacoby P, Downs J, Marsh ED, Leonard H, Pestana‐Knight E, Rajaraman R, Weisenberg J, Suter B, Olson HE, Dana P, Hong W, Prange E, Benke TA, Demarest S (2024) Psychometric evaluation of clinician- and caregiver- reported clinical severity assessments for individuals with CDKL5 deficiency disorder, Epilepsia, 65(10),3064-3075. DOI: 10.1111/epi.18094.
https://pubmed.ncbi.nlm.nih.gov/39190322/
Background
Current research is leading towards treatments that target the condition at its cause, such as gene therapies. To support these trials and measures small but important changes with these treatments, we need valid and reliable measures to assess how severe a child’s symptoms are. Previously, we worked with clinicians and parents to develop the CDKL5 Clinical Severity Assessment (CCSA; one filled out by clinician and one by parent). This study tested to see how the CCSA-Clinician and CCSA-caregiver worked for children with CDD.
What we did
We tested the following measures with nearly 200 individuals with CDD. Some visited one of 8 Center of Excellence clinics in USA and some provided information through the International CDKL5 Disorder Database:
· The Clinician reported clinical severity assessment (CCSA-Clinician): This measure is completed by a trained doctor after examining a child in clinic.
· The Caregiver reported clinical severity assessment (CCSA-Caregiver): This measure is completed by caregivers based on their everyday observations at home for the last 30 days.
We analysed how well the questions in each measure worked. We also tested how reliable the measures were by having some caregivers and doctors complete them a second time after one month. This helped us fine-tune the measures using the items that best reflected the range of experiences seen in children with CDD.
What we found
For the CCSA-Clinician, the items described Movement, Communication, and Vision. For the CCSA-Caregiver, the items described Seizures, Behaviour, Alertness, and Feeding.
The items fitted together well for both measures and were able to detect differences between children with more or less severe symptoms. Families and doctors could reliably use these measures again after a month and get similar results.
Why this is important
These measures will help researchers and clinicians track how individuals with CDD are doing over time, and whether a treatment is making a difference. The measures collect clinical and parent observations, providing a well-rounded picture of each child. These measures are ready to be used in clinical trials and could also be adapted for other similar conditions.
Modification of a parent-report sleep scale for individuals with CDKL5 deficiency disorder: a psychometric study
Saldaris JM, Demarest S, Jacoby P, Olson HE, Maski K, Pestana-Knight E, Dana P, Rajaraman R, Suter B, Weisenberg J, Leonard H, Marsh ED, Benke TA, Downs J (2024) Modification of a parent-report sleep scale for individuals with CDKL5 deficiency disorder: a psychometric study. Journal of Clinical Sleep Medicine, 20(12), 1887-1893. DOI: 10.5664/jcsm.11244.
https://pubmed.ncbi.nlm.nih.gov/38963064/
Background
Sleep problems are very common in children with CDD. Many families report that their child has trouble falling asleep, wakes often during the night, or is very sleepy during the day. These sleep issues can affect the child’s wellbeing, learning, and behaviour, and place strain on parents and caregivers. To understand and improve sleep in CDD, researchers need measures that can accurately measure these problems. One commonly used measure is the Sleep Disturbance Scale for Children (SDSC), but it was originally developed for typically developing children. This study looked at how the SDSC could be used for children with CDD.
What we did
We worked with data from 125 families of children and adults (aged 3 years and older) with CDD who attended one of the CDKL5 Centre of Excellence clinics. Parents completed the SDSC, which asked about sleep habits and challenges. We focused on two parts of the measure, 1) Night-time sleep difficulties with insomnia and 2) Excessive daytime sleepiness, as these were the most relevant domains for children with CDD.
We analysed how well the questions worked for CDD by checking how well the questions fit together to describe the concepts of insomnia and excessive daytime sleepiness.
What we found
Three original SDSC questions did not fit with the other questions. For example, asking if the child feels anxious at bedtime or if they can’t move when they wake up could have been hard for parents to observe. After removing these, the remaining ones fitted together to give reliable information about insomnia and excessive daytime sleepiness.
Why this is important
The sleep scale was modified to reflect parent observations of their child’s sleep. This means it can be used with more confidence in both clinical care and future research. Good sleep is essential for the health and quality of life of children with CDD and their families, and having the right measures to assess it is a crucial step forward.
Adapting a measure of gross motor skills for individuals with CDKL5 deficiency disorder: A psychometric study
Saldaris JM, Jacoby P, Marsh ED, Suter B, Leonard H, Olson HE, Rajaraman R, Pestana-Knight E, Weisenberg J, Price D, Drummond C, Benke TA, Demarest S, Downs J (2024) Adapting a measure of gross motor skills for individuals with CDKL5 deficiency disorder: A psychometric study. Epilepsy Research, 200, 107287. DOI: 10.1016/j.eplepsyres.2024.107287.
https://pubmed.ncbi.nlm.nih.gov/38237219/
Background
Many children with CDD experience challenges with motor skills, such as sitting, standing, and walking. These skills are important to measure, for clinical care and in trials. However, there hasn’t been a measure specifically designed to measure gross motor skills in children with CDD. This study aimed to adapt an existing measure developed for Rett syndrome to better reflect the abilities and needs of people with CDD. This is a video measure which allows remote video collection which allow motor skills to be filmed from home.
What we did
We looked at a range of gross motor measures in the literature and talked with parents with a child with CDD to make changes to the video-based measure developed for Rett syndrome, to better suit people with CDD. We developed instructions for parents to follow. Families from around the world filmed their children doing specific motor tasks at home—like lying, sitting, standing, or walking—and uploaded video clips from their phone to our secure computers at The Kids Research Institute Australia. We tested how well this new version worked by checking how the tasks fitted together to describe the concept of gross motor function, and whether it gave reliable results (e.g., the same score is achieved by different raters), could tell the difference between individuals with different abilities, and if parents found it practical and acceptable to use.
What we found
The final version of the measure, called the Gross Motor–Complex Disability (GM-CD) scale. There are 17 items. The GM-CD worked well in measuring a wide range of motor abilities in CDD, from those with very limited function to those who could walk independently. Parents were positive about the motor video process in their everyday settings, and nearly all found the instructions to be clear. GM-CD scores were different for children of different ages, and walking and communication abilities. Scores were consistent for different raters or when the same rater scored twice on different occasions. One item (lifting the head while lying on the stomach) didn’t work as well and may not be useful in future versions.
Why this is important
The GM-CD gives researchers and clinicians a reliable way to measure movement skills in individuals with CDD. Information can be collected remotely from the person’s usual setting. GM-CD is designed for individuals with complex needs and may be able to capture progress that standard measures might miss.
Initial Validation and Reliability of the CDKL5 Deficiency Disorder Hand Function Scale (CDD-Hand)
Saldaris J, Leonard H, Jacoby P, Marsh ED, Benke TA, Demarest S, Downs J (2022) Initial validation and reliability of the CDKL5 Deficiency Disorder Hand Function Scale (CDD-Hand). Journal of Child Neurology, 37(6), 541-547. DOI: 10.1177/08830738221091044.
https://pubmed.ncbi.nlm.nih.gov/35422141/
Background
Children with CDD may have difficulties with hand function, which can make everyday tasks like eating, playing or holding toys difficult. We need reliable ways to measure hand function in CDD, for clinical care and for testing new treatments in clinical trials. While a similar hand function scale exists for Rett syndrome, no measure has been specifically adapted for children with CDD, which takes into account cortical visual impairment (CVI) which occurs commonly in people with CDD.
What we did
We adapted an existing hand function scale (originally developed for Rett syndrome) for children with CDD. We talked with expert clinicians and families to tailor the instructions, particularly to account for CVI and develop instructions for parents.
We invited 86 parents to film their child grasping and holding everyday large (hand-sized) and small objects, with or without help. Two trained raters scored the videos to test how consistently the scale could be used. One rater completed the scoring on two separate occasions. Parents also gave feedback about how easy and useful they found the process.
What we found
The new scale, called CDD-Hand, was easy for most families to use in their everyday setting. Parents found the instructions clear, and the process was acceptable for a range of ages and motor abilities. The video scores were consistent between and within the raters, showing the scale is reliable. The hand function abilities varied widely among the children, and the scale reflected these differences, even among those with very limited skills.
Why this is important
This study provides an important first step toward having a validated and reliable measure to assess hand function in people with CDD. Specifically, having this measure is essential for clinical trials testing new treatments. It also gives families and clinicians a practical way to track small but meaningful changes in hand function using videos filmed at home. This approach supports remote participation in assessments, which is especially important for rare conditions like CDD.
Validating the Communication and Symbolic Behavior Scales-Developmental Profile Infant-Toddler Checklist (CSBS-DP ITC) Beyond Infancy in the CDKL5 Deficiency Disorder
Saldaris J, Leonard H, Wong K, Jacoby P, Spence M, Marsh ED, Benke TA, Demarest S, Downs J, Jenny (2024) Validating the Communication and Symbolic Behavior Scales–Developmental Profile Infant–Toddler Checklist (CSBS–DP ITC) Beyond Infancy in the CDKL5 Deficiency Disorder. Journal of Autism and Developmental Disorders, 54(7), 2526-2535. DOI: 10.1007/s10803-023-06002-w.
https://pubmed.ncbi.nlm.nih.gov/37184758/
Background
Children with CDD often experience challenges with communication. While there are some measures that have been used to assess communication in severe disability, but none have been validated for people with CDD. Having a good way to measure communication is crucial for tracking progress and testing whether new treatments, like gene therapy, are making a real difference in communication.
What we did
We tested a parent measure called the Communication and Symbolic Behavior Scales–Developmental Profile Infant-Toddler Checklist (CSBS-DP ITC), which was originally designed to screen communication in infants and toddlers. We wanted to see if it could still be useful for children and young adults with CDD. In our study, 150 families who were registered with the International CDKL5 Disorder Database filled out the CSBS-DP ITC measure. The measure has 24 items that describe Social, Speech and Symbolic communication behaviours. 73 of parents completed the CSBS DP ITC a second time four weeks later so we could test consistency of answers. We also looked at whether the scores were different for children with different functional abilities, such as whether they could walk or grasp objects with their hands.
What we found
The results showed that many children with CDD had very low scores. More than half of the items often received a score of zero. This suggests that there is a “floor effect.” Scores were consistent when repeated after 4 weeks (showing high reliability). Children who walked, spoke words, or could grasp objects had higher CSBS scores. Also, the original three-parts did not give different information about the child’s communication. Calculating the total score gave similar information.
Why this is important
This is the first time a communication measure has been studied in a large group of children and young adults with CDD. While the measure did pick up on broad differences in communication ability, it may not be the best choice for tracking smaller improvements of people with severe challenges. This is important to know as new therapies become available, whereby researchers and families need measures that can show progress, no matter how small. Our study highlights the need for better communication measures tailored for children with CDD.
Communication of individuals with CDKL5 deficiency disorder as observed by caregivers: A descriptive qualitative study
Keeley J, Benson-Goldberg S, Saldaris J, Lariviere J, H Leonard, Marsh ED, Demarest ST, Benke TA,
Jacoby P, Downs J (2024) Communication of individuals with CDKL5 deficiency disorder as observed by caregivers: A descriptive qualitative study. American Journal of Medical Genetics Part A, 194(7), p.e63570-n/a. DOI: 10.1002/ajmg.a.63570.
https://pubmed.ncbi.nlm.nih.gov/38425131/
Background
We found that the CSBS-DP ITC measure was not well suited for measuring communication in CDD in a previous study. This study aimed to better understand how individuals with CDD communicate in their daily lives, as seen by their caregivers, to tell us what to measure.
What we did
We interviewed 23 caregivers (mostly mothers) of individuals aged 2 to 30 years with CDD. The caregivers were asked to describe how their child communicates, including the methods they use, the reasons for their communication, and how they engage with others. The interviews were analysed to find common patterns and themes to give a rich picture of communication in CDD across different ages and levels of ability.
What we found
Caregivers described a wide range of communication methods, including body movements, facial expressions, vocal sounds, and use of devices or sign language. Most individuals in the study did not use spoken words, but they still found ways to express themselves meaningfully through non-verbal communication.
Three main themes emerged:
1. Modes of communication – how the child communicates (e.g., eye gaze, gestures, sounds, use of a device).
2. Purpose and meaning – why they communicate (e.g., to express wants, needs, emotions, or to interact socially).
3. Reciprocal exchanges – the ways they take part in back-and-forth interactions with others.
The study also found that communication can vary day to day depending on health, mood, medications, and the familiarity of the setting or communication partner. Caregivers sometimes found it hard to interpret what their child was trying to communicate, especially when signals were subtle or inconsistent.
Why this is important
This study helps build a clearer picture of how individuals with CDD communicate, highlighting that there are many ways that communication is purposeful and meaningful. These insights will help us to develop better ways to measure communication in CDD. This, in turn, can help ensure that new therapies are evaluated in ways that reflect the true abilities and needs of individuals with CDD and their families.
Parent-reported outcome measures evaluating communication in individuals with rare neurodevelopmental disorders: A systematic review
Saldaris JM, Ayalde J, Kankanange S, Keeley J, Leonard H, Jacoby P, Marsh ED, Benke TA, Demarest ST, Downs J (2024) Parent-reported outcome measures evaluating communication in individuals with rare neurodevelopmental disorders: A systematic review. International Journal of Language & Communication, 59(6), 2528-2553. DOI: 10.1111/1460-6984.13100.
https://pubmed.ncbi.nlm.nih.gov/39141588/
Background
Many children with rare neurodevelopmental disorders (RNDDs), such as CDD, face significant challenges with communication. Caregiver surveys have shown that communication difficulties are a top concern for families. As researchers work to develop new treatments, including gene therapies, it's essential to have reliable measures that can measure whether communication is improving. This review looked at what parent-report communication measures are being used in RNDD research and whether they have been properly tested to ensure they are suitable for this population.
What we did in this review
We systematically searched for studies that used parent-reported communication assessments in individuals with RNDDs. First, we identified which measures had been used in published studies and clinical trials. Then, we looked at whether those measures had been tested for whether they were accurate, reliable, and sensitive to changes, in people with RNDDs. We evaluated each measure using an international standard (called the COSMIN checklist).
What we found
Sixteen different communication measures were found, but only six had any testing (validation) data in RNDD populations. Of the 6 measures found, the Vineland Adaptive Behavior Scales (VABS) was most commonly used. The Observer-Reported Communication Ability (ORCA) had strong evidence that worked well for people with Angelman syndrome and Rett syndrome. Understanding how well the measures worked was limited by studies being small and limited in the scope of their testing.
Why this is important
This review is a critical step in understanding what next to do to ensure that families, researchers and clinicians have better measures to track communication for individuals with RNDDs. As new therapies are developed, researchers must be confident that the measures they’re using can capture small but meaningful improvements.
Psychometric properties of QI-Disability in CDKL5 Deficiency Disorder: Establishing readiness for clinical trials
Saldaris J, Jacoby P, Leonard H, Benke TA, Demarest S, Marsh ED, Downs J (2023) Psychometric properties of QI-Disability in CDKL5 Deficiency Disorder: Establishing readiness for clinical trials. Epilepsy & Behavior, 139, 109069. DOI: 10.1016/j.yebeh.2022.109069.
Negative impact of insomnia and daytime sleepiness on quality of life in individuals with the cyclin-dependent kinase-like 5 deficiency disorder
Downs J, Jacoby P, Saldaris J, Leonard H, Benke T, Marsh ED, Demarest S (2021) Negative impact of insomnia and daytime sleepiness on quality of life in individuals with the cyclin-dependent kinase-like 5 deficiency disorder. Journal of Sleep Research, 31(5), p.e13600-n/a. DOI: 10.1111/jsr.13600.
https://pubmed.ncbi.nlm.nih.gov/35415902/
Background
Challenges with health and wellbeing can impact the quality of life of children with CDD. A parent-reported measure, Quality of Life Inventory-Disability (QI-Disability), has previously been developed for children with intellectual and developmental disabilities. QI-Disability has 32 items that measures quality of life across six areas (physical health, positive emotions, negative emotions, leisure and the outdoors, social interaction, and independence).
What we did
Across two studies, we worked with over 150 families registered with the International CDKL5 Disorder Database. Caregivers filled out the QI-Disability and other surveys (e.g., sleep scale) and we
1) Evaluated the QI-Disability for CDD - check whether it is consistent, reliable, and valid.
2) Explored how sleep problems are associated with quality of life - particularly insomnia (trouble falling or staying asleep) and daytime sleepiness, which are common and distressing symptoms in people with CDD.
What we found
· The QI-Disability measure was a reliable and valid measure of quality of life in CDD.
· Factors like functional abilities and number of antiseizure medications, but not seizure frequency, were strongly linked to quality of life scores.
· Sleep problems were strongly associated quality of life. Excessive daytime sleepiness was especially linked to lower total quality of life, physical health and higher negative emotions scores. Insomnia was associated with higher negative emotions scores.
· Using prescribed sleep medications had little influence on the negative associations between poor sleep and quality of life.
Why this is important
Together, these two studies show that QI-Disability is a suitable way to measure quality of life for people with CDD. This is crucial for clinical trials of new treatments as researchers and regulators need to know that the measures used in trials truly reflect changes that matter to families. In everyday care, QI-Disability can also help track how a child is doing over time, guide support planning, and ensure that health services are focusing on the outcomes that matter most to families.
International CDKL5 Clinical Research Network
This website uses cookies.
We use cookies to analyze website traffic and optimize your website experience. By accepting our use of cookies, your data will be aggregated with all other user data.