CLCN4-related Neurodevelopmental Condition

Communication difficulties represent the most common feature in this group, affecting 100% of males and 95% of de novo females in the largest cohort studied to date (4). Difficulties understanding and expressing language are a consistent challenge across the group. However, the trajectory of speech and language development varies across people. Some children produce their first words within typical development (around 1 year old), while some adults have not yet said their first word (5). In contrast, the progression to two-word phrases and sentences was consistently delayed, which in turn prevented communication development from a need based, to functional social expression. This was identified as an important barrier in this group, who all showed a strong social desire to communicate.

• Learning difficulties: Most people with CLCN4-NDD experience mild-to-severe cognitive impairment (1,2).
• Mental health and behaviour: Autism spectrum disorder (ASD) is frequently reported in this group, as well as attention difficulties, anxiety, and mood conditions (3,6)
• Motor (movement) disorder: Gross and fine motor delays are common in this group. Infantile hypotonia (low tone) is also an important feature, that can often affect the oral-motor structures required for speech and feeding.
• Epilepsy and seizures: Epilepsy affects nearly 50% of people with CLCN4- Seizures often present by 3-years-old and can be resistant to standard antiseizure medications (3,7,8)
• Brain changes: MRI studies often find changes involving the white matter of the brain. The corpus callosum is often found to be thinner, and occasionally absent in affected people (1,9,10).
• Gastrointestinal difficulties: Reflux disorders and chronic constipation are increasingly being recognised in this group, affecting growth milestones especially in de novo De novo females are also reported to experience greater feeding challenges than males or inherited females. Nutritional supplementation via a gastronomy tube is sometimes required to support adequate nutrition (6).

Most people with CLCN4-NDD use a combination of verbal speech and augmentative and alternative communication (AAC), including low tech (gesture, key word sign), and high tech (such as text-to-speech applications). Communicating wants and needs with 1–2 word phrases, such as requesting or rejecting objects/actions, was a strength in this group. However, social communication was often limited, despite a strong desire to communicate (5). This was often due to a combination of language delay, cognitive impairment affecting working memory, motor speech difficulties that impact speech intelligibility, and a lack of support to promote AAC use for question asking and social connection.

People with CLCN4-NDD require comprehensive and dynamic assessment to inform the most appropriate diagnosis and therapy options. These assessments should include language (expressive and receptive), speech (sound stimulability, intelligibility, speech errors), oral-motor assessment, and social communication. Frequent reassessment is also recommended to monitor progress and ensure speech, language, and social communication goals are relevant and meaningful to the person and their family (11).

There is currently no research on speech and language therapies specific for people with CLCN4-NDD. However, evidence-based practice must include a person and family centred approach to assessment and therapies that are tailored to the person’s strengths and challenges.

Consistent reports of speech and language delays in CLCN4-NDD, especially regarding the transition from first words to 2-4 word phrases, emphasise the benefit of early speech pathology intervention to support language learning and early speech milestones (5). Given the persisting nature of speech challenges, AAC should be implemented early, and regularly reassessed to ensure the system provided is relevant to the child, family, educational and social environment. AAC interventions may involve low-tech approaches (e.g., key word sign, communication books). In some instances, more than one AAC system may be required to support the person’s communication across environments and communication settings. Education to families about the benefit of AAC to support overall language development, and provide an opportunity for social connection, is essential. For people with spoken language, motor speech therapy that follows motor learning principles will support speech intelligibility and naturalness.

Assessment/evaluation

Speech assessment should include:

• Speech production skills across single sound, word, and sentence level. This will help specific diagnosis (e.g., phonological disorder, articulation disorder, apraxia of speech).
• Receptive, expressive, and social language skills.
• AAC assessment to determine the best system for your child’s needs.
• Literacy assessment.
• Environmental supports to optimise practical communication needs (e.g., visual schedules, desk position in the classroom etc.).

• The plain language summary of our research on CLCN4-NDD is available here
• For information on speech and language abilities and CLCN4-NDD, please see our CLCN4 NDD Fact Sheet