CTNNB1 Neurodevelopmental Syndrome - Natural History Study

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages Any age
• All sexes
• No healthy volunteers
• Child, Adult, Older adult

Study population: The study will enroll individuals with a genetically confirmed pathogenic variant in the CTNNB1 gene consistent with a diagnosis of CTNNB1 neurodevelopmental syndrome. Each participant must have at least one parent or legal guardian available to support participation in the study. Families with more than one affected individual are eligible, and multiple participants from the same family may be enrolled.

Trial locations and contacts

2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

About this study

Official title: Dragonfly Study: An International, Prospective, Longitudinal, Observational Natural History Study of Children and Adults Living With CTNNB1 Neurodevelopmental Syndrome

Conditions

CTNNB1 Neurodevelopmental Syndrome

Being tested

A General Medical and Neurological Assessment, World Health Organisation (WHO) Motor Milestones, Burke-Fahn-Marsden Dystonia Rating Scale, Spastic Paraplegia Rating Scale, 5. CTNNB1-Related Neurodevelopmental Disorder (NEDSDV) Cardiac Health Questionnaire

Keywords

CTNNB1 neurodevelopmental syndrome, Natural History Study, CTNNB1 gene mutation, Autism Spectrum Disorder, Beta-catenin, Developmental Delay

Medical subject headings

Autism Spectrum Disorder, Learning Disabilities

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• A General Medical and Neurological AssessmentDiagnostic test

  Clinical assessments will consist of gathering demographic data, detailed relevant medical history, and parents' perspectives on treatment priorities, clinical trial interest, and acceptability of risk in future clinical trials. A general medical and neurological examination will be performed by a trained and skilled physician with a valid Good Clinical Practice Certification.

• World Health Organisation (WHO) Motor MilestonesDiagnostic test

  Ages of six WHO Motor milestones achievements - sitting without support, hands and knees crawling, standing with support, walking with support, standing independently, and walking independently - will be assessed. The age of milestone achievement will be compared to normative variations in age as recommended by the WHO (WHO, 2006).

• Burke-Fahn-Marsden Dystonia Rating ScaleDiagnostic test

  The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS; Burke, Fahn, Marsden et. al, 1985) is a universally applied biomarker for the severity of dystonia in children and adults. The scale consists of a movement and disability subscale (Burke-Fahn-Marsden Movement Scale [BFMMS] and Burke-Fahn-Marsden Disability Scale [BFMDS], respectively. Only the BFMMS will be assessed. The BFMMS measures dystonia in nine body regions (including the eyes, mouth, speech and swallowing, neck, trunk, arms, and legs) with scores ranging from 0 (minimum) to 120 (maximum).

• Spastic Paraplegia Rating ScaleDiagnostic test

  The Spastic Paraplegia Rating Scale (SPRS; Schüle et al., 2006) is a 13-item scale used to measure disease severity in spastic paraplegia. The items include walking distance without pause, gait quality, maximum gait speed, climbing stars, arising from chair, spasticity of hip adductor and knee flexion muscles, weakness of hip abduction and foot dorsiflexion, contracture of lower limbs, pain related to spasticity, and bladder and bowel function. Each item has a score ranging from 0 to 4, where 0 represents no dysfunction and 4 represents most severe dysfunction. The score result is calculated by adding single scores of each of the 13 items. The total score varies between 0 (no dysfunction) and 52 (most severe dysfunction).

• 5. CTNNB1-Related Neurodevelopmental Disorder (NEDSDV) Cardiac Health QuestionnaireDiagnostic test

  In a recent study (Sinibaldi et al., 2023), several patients with NEDSDV showed heart abnormalities. To expand on that, investigators developed a parent report questionnaire on the presence of potential heart defects.

• 10m Walk-Run TestDiagnostic test

  The 10m Walk-Run Test is is a performance measure used to assess walking or gait speed in meters per second over a short distance. It involves measuring the time it takes for a person to walk the distance, with results reported in meters/second (m/s). The patient's ability to walk at both comfortable and fast speeds can be measured, and assistive devices can be used. The test will be performed in ambulant children by an experienced physiotherapist.

• The Nine Hole Peg TestDiagnostic test

  The Nine-Hole Peg Test (9-HPT; Kellor et al., 1971) is a standardized, quantitative assessment used to measure finger dexterity. It is administered by asking the client to take the pegs from a container, one by one, and place them into holes on the board as quickly as possible. The 9-HPT has been validated for children above the age of 4 years (Poole et al., 2006). The test will be performed in children over 4 years old by a trained investigator.

• The Gross Motor Function Classification SystemDiagnostic test

  The Gross Motor Function Classification System (GMFCS; Palisano, Rosenbaum, Bartlett, Livingston, 2007) is a 5-level classification system that describes the gross motor function of children and youth with cerebral palsy on the basis of their self-initiated movement with particular emphasis on sitting, walking, and wheeled mobility. Distinctions between levels are based on functional abilities, the need for assistive technology, including hand-held mobility devices (walkers, crutches, or canes) or wheeled mobility, and to a much lesser extent, quality of movement. The questionnaire is available for four age groups of children and youth: 2 to < 4 years, 4 to < 6 years, 6 to < 12 years, and 12 to 18 years.

• Bayley Scales of Infant and Toddler Development-4: Fine Motor, Gross Motor, Language, and Cognitive ScalesDiagnostic test

  Bayley Scales of Infant and Toddler Development-4 (BSID-4; Bayley et al., 2019) is an extensive formal developmental assessment tool for diagnosing developmental delays in early childhood. It consists of 419 items across 5 scales, each of which can be administered separately - Cognitive Scale (81 items), Language Scale (79 items), Motor Scale (104 items), Social-Emotional Scale (35 items), and Adaptive Behavior Scale (120 items). In our study, Motor, Language and Cognitive scales will be performed by a trained psychologist - if possible, at the patient's home country and in their native language.

• Wechsler Non-Verbal Scale of AbilityDiagnostic test

  Wechsler Nonverbal Scale of Ability (WNV, Wechsler et al., 2006) is a standardized, individually administered test designed to assess general cognitive ability in individuals aged 4 to 21 years, particularly those who may have language, cultural, or communication challenges that make traditional verbal IQ tests less appropriate. It consists of six different subtests that are utilized based on the participant's age. In our study, the test will be performed in children above the age of 4 years by a trained psychologist - if possible, at the patient's home country and in their native language.

• The Vineland Adaptive Behaviour Scales - 3Diagnostic test

  The Vineland Adaptive Behaviour Scales (VABS-3; Sparrow et al., 2018) is a standardized assessment tool that utilizes semi-structured interview to measure adaptive behaviour and support the diagnosis of intellectual and developmental disabilities, autism, and developmental delays. It is validated for children of all ages and consists of five primary domains (Communication, Daily Living Skills, Socialization, Motor Skills, and Adaptive Behavior Composit).

• Aberrant Behaviour Checklist -CommunityDiagnostic test

  The Aberrant Behaviour Checklist-Community (ABC-C) is a parent report behavioural rating scale designed to assess problem behaviours in individuals with developmental disabilities. It consists of 58 likert-type items across five domains (Irritability, Social Withdrawal, Stereotypic Behaviour, Hyperactivity, and Inappropriate Speech) with responses ranging from "not at all a problem" to "the problem is severe in degree".

• The Modified Checklist for Autism in ToddlersDiagnostic test

  The Modified Checklist for Autism in Toddlers (M-CHAT; Robins, Fein, \& Barton, 2009) is a 2-stage parent report screening tool to assess risk for autism spectrum disorder (ASD). It is validated for children 16-30 months old.

• The Autism Spectrum Quotient Questionnaire -Children's VersionDiagnostic test

  The Autism Spectrum Quotient-Children's Version (AQ-Child; Auyeung, Baron-Cohen, Wheelwright \& Allison, 2008) is a parent report questionnaire that aims to quantify autistic traits in children 4 - 11 years old. It contains 50 likert-type items with responses ranging from "definitely agree" to "definitely disagree".

• The Autism-Spectrum Quotient (AQ)-Adolescent VersionDiagnostic test

  The Autism Spectrum Quotient-Children's Version (AQ-Child; Auyeung, Baron-Cohen, Wheelwright \& Allison, 2008) is a parent report questionnaire that aims to quantify autistic traits in children 12 - 15 years old. It contains 50 likert-type items with responses ranging from "definitely agree" to "definitely disagree".

• Continuous Movement Monitoring (Actimyo/Syde)Diagnostic test

  Continuous movement data will be collected using the ActiMyo/Syde® device (Servais et al., 2022), which is attached to the ankles and uses magneto-inertial sensors to quantify movement. At the first study visit, 20 ambulant patients older than 2 years old will be fitted with a Syde device to each ankle and their carers will be provided with training on use and care of the device. It will be worn for 30 days and then repeated in one year.

• Sleep Disturbance Scale for ChildrenDiagnostic test

  The Sleep Disturbance Scale for Children (SDSC; Bruni et al., 1996) is a parent report questionnaire used to identify sleep disorders in children. It contains 26 likert-type items with responses ranging from "never" to "always (daily)". The items are divided in six categories - disorders of initiating and maintaining sleep, sleep breathing disorders, disorders of arousal/nightmares, sleep-wake transition disorders, disorders of excessive somnolence, and sleep hyperhidrosis (nighttime sweating).

• Seizure DiaryDiagnostic test

  A 28-day seizure diary is a self-reported tool used to record seizure activity to obtain insight into the patient's seizure triggers and severity, monitor medication side effects, and promote medication adherence. Patients are asked to record their seizure occurrence, duration, and type of seizures.

• 30min EEG RecordingDiagnostic test

  Recording will take place in the hospital's EEG department in a quiet room with low-light levels. If children will be unable to lay still, melatonin or dexmedetomidine may be used, as per standard department protocol. An EEG cap with international system 10-20 electrodes, ECG and respiratory electrodes will be placed on the head and chest respectively. Data will be recorded for at least 30 minutes, and an attempt will be made to capture both wakefulness and sleep. Intermittent photic stimulation will be performed as per standard protocol.

• PedsQL Family Impact ModuleDiagnostic test

  The PedsQL Family Impact Module is a parent report standardized questionnaire designed to measure the impact of paediatric chronic health conditions on the health-related quality of life (HRQOL) of parents and the functioning of the family as a whole. It consists of 36 likert-like items over 8 domains (Physical Functioning, Emotional Functioning, Social Functioning, Cognitive Functioning, Communication, Worry, Daily Activities, Family Relationships). The items are scored with responses ranging from "never a problem" to "always a problem".

• PedsQL Core ModuleDiagnostic test

  The PedsQL™ (Pediatric Quality of Life Inventory) Core Module is a health-related quality of life (HRQOL) questionnaire designed for children and adolescents. It assesses physical, emotional, social, and school functioning by using 23 likert-like items across 4 subscales (Physical Functioning, Emotional Functioning, Social Functioning, School Functioning). The items are scored with responses ranging from "never a problem" to "always a problem". Items differ across age groups - toddlers (2-4 years), young children (5-7 years), children (8-12 years), teens (13-18 years), and young adults (18-25 years). In toddlers, the parents serve as proxy, and in young children, a three-point scale with faces is used instead of likert-type responses.

• Blood Sample CollectionDiagnostic test

  Venepuncture will be performed by a qualified member of the research team on all participants at each visit and 2x 5ml of blood will be collected (< 0.8 ml/kg) for analysis of DNA methylation and RNA expression, and analysis of serum for neurofilaments, b-catenin, and zinc. All blood samples will be labelled with the study ID and visit number and processed at the laboratory of the UMCL following the protocol "CTNNB1".

• Optical Coherence TomographyDiagnostic test

  To test for FEVR, the participants will be asked to perform Optical Coherence Tomography in their home countries at baseline and before or after every subsequent visit. OCT will only be performed in patients who will be able to cooperate - focus gaze for about 5 seconds.

• Brain MRIDiagnostic test

  If a participant has had a brain MRI performed prior to enrolling in our study, pictorial data will be analysed. If the participant will plan to have an MRI performed as a standard procedure in their native country, they will be asked to follow the CTNNB1 MRI protocol: T1 MPRAGE sequence, 3D FLAIR sequence, T2 axial planeartane, SWI, DWI, and DTI with at least 64, but preferably 90 diffusion directions. MRI will not be performed on site.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. Collection of relevant retrospective and prospective clinical data in patients with CTNNB1 syndrome via physical assessments, scales, and questionnaires.

   The aim of the Dragonfly study is to characterise and monitor the neurodevelopment of children and adults diagnosed with CTNNB1 syndrome through an international collaborative effort. Gaining comprehensive understanding of the mental, physical and social development of people with CTNNB1 neurodevelopmental syndrome and how their symptoms and abilities change over time will help improve and standardize care for these patients, as well as facilitate future research and clinical trials design.

   Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted11 Sep 2025
2. Study start14 Jun 2024
3. Primary completionJun 2029 (estimated)
4. Study completionJan 2030 (estimated)

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Publications (2)Papers the sponsor has linked to this study.
• Other trials for CTNNB1 Neurodevelopmental SyndromeStudies of the same condition, open and under way.
• More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.