International Clinical Evidence-Based Guideline for Kleefstra Syndrome (2026)
The document that you find further down this page sets out the first internationally agreed clinical guidelines for the care of people with Kleefstra syndrome type 1 (KLEFS1), a rare genetic neurodevelopmental condition caused by changes to the EHMT1 gene.
Why this guideline exists
Until now, care for people with Kleefstra Syndrome has varied widely between countries and clinicians. Families often face fragmented support, delayed diagnosis, and uncertainty about best practice. This guideline was created to:
- Reduce inequality in care
- Improve quality of life for individuals and families
- Give clinicians a clear, minimum international standard of care
- Support shared decision-making with families
It was developed by a global consortium of 43 experts and parents from 15 countries, combining medical evidence with lived experience.
What the guideline covers (in real terms)
The guideline includes 66 practical recommendations covering the whole lifespan. Key areas include:
1. Diagnosis and genetics
- Confirms that genome or exome sequencing should be first-line testing
- Explains different genetic causes and why some cases are harder to detect
- Covers inheritance, recurrence risk, and prenatal diagnosis
- Emphasises referral to specialist genetics teams after diagnosis
2. Mental health, behaviour and regression
- Mental health conditions are very common in Kleefstra syndrome
- Anxiety, depression, autism, OCD-type behaviours and regression are highlighted
- Recommends annual mental health screening
- Regression (loss of skills in adolescence/adulthood) is recognised as a key risk and needs urgent specialist assessment
3. Neurology, epilepsy and sleep
- Epilepsy affects up to 40% of individuals
- Clear guidance on when EEGs and brain MRIs are needed
- Sleep problems affect over half of individuals and can be an early warning sign of regression
- Strong emphasis on early intervention for sleep issues
4. Communication and development
- Speech and language difficulties are almost universal
- Augmentative and Alternative Communication (AAC) is strongly recommended and does not prevent speech development
- Annual speech and language reviews in childhood
- Communication support remains important into adulthood
5. Vision and hearing
- High rates of hearing loss and visual impairment
- Regular screening is essential, especially in early childhood
- Cerebral visual impairment (CVI) is recognised but often under-diagnosed
6. Physical health
- Covers heart conditions, growth, metabolism and obesity
- Recommends routine heart checks and ECGs in adulthood
- Highlights high risk of obesity and metabolic issues
- Constipation is common, often severe, and needs proactive management
7. Family support and transition to adulthood
- Clinicians should actively check family wellbeing
- Signposting to patient organisations and peer support is essential
- Transition planning to adult services should start in adolescence
Why this document matters
- It validates families’ experiences (sleep, regression, constipation, mental health are all formally recognised)
- It gives clinicians confidence and consistency
- It strengthens the case for early intervention and multidisciplinary care
- It provides a solid foundation for advocacy, funding bids, and service development
- It will be reviewed every five years, so care evolves with new evidence
This guideline sets out the first global, evidence-based standard of care for people with Kleefstra syndrome, covering diagnosis, health, communication, mental health, and family support across the lifespan. It’s a 39 page document so put the kettle on before you download it!