Kleefstra syndrome is a rare genetic condition caused by disease-causing genetic changes (variants) affecting the EHMT1 gene.¹ Common features of Kleefstra syndrome are differences in learning profile and speech and language development.² Gastrointestinal conditions, difficulties staying asleep and epileptic seizures are health issues for many individuals. There are also a range of other rarer physical, emotional wellbeing and behavioural issues that can be associated with Kleefstra syndrome. Whilst some of these features can be recognised at birth, other symptoms might develop during childhood or after puberty.³ Kleefstra syndrome can affect both males and females.² It is important to recognise that although there are some common symptoms, no two people with Kleefstra syndrome have the same symptoms, and that there are many medical, developmental and educational therapies and supports which, if in place, can help each individual live to their full potential. Appropriate support and care of individuals with Kleefstra syndrome involves lifelong care from a multidisciplinary medical team. ²

Synonyms: ^1,2 9q34.3 Microdeletion Syndrome, 9qSTDS, 9q Subtelomeric Deletion Syndrome; KS; KLEFS

Please note that KMT2C-related condition, previously known as Kleefstra syndrome 2, is a separate genetic condition.

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:261494 Kleefstra syndrome

ICD-11: LD2F.1Y Other specified syndromes with multiple structural anomalies, not of environmental origin

2026 ICD-10-CM Diagnosis Code Q87.86: Kleefstra syndrome

Characteristic features of Kleefstra syndrome include: ^1-6

• learning differences including developmental delay and intellectual disability
• childhood hypotonia (low muscle tone)
• speech and language challenges including childhood apraxia of speech (difficulties with the production of sounds).
• feeding challenges and gastrointestinal symptoms including gastroesophageal reflux, constipation, and other conditions related to gut dysmotility, including eosinophilic oesophagitis (EoE) and gastroparesis (slow emptying of the stomach)
• difficulties with sleep patterns, both falling asleep and staying asleep
• features on the autism spectrum
• subtle yet distinctive facial features

Individuals with Kleefstra syndrome may be born with differences in the structure of their heart (cardiac) and kidneys (renal). ^2,3 Other symptoms can include recurring seizures (epilepsy), middle ear infections that can impact hearing if not treated, respiratory infections (chest and throat infections).

A proportion of individuals may develop an acute change of their symptoms, usually starting with a severe change in sleep pattern (complete disruption of the sleep wake cycle for at least 48 hours). This most commonly occurs during or after puberty. It can be triggered by a range of stresses including medical conditions and psychosocial changes (such as moving house).⁷ This is typically associated with changes in behaviour (such as aggressive outbursts and temper tantrums) and can result in loss of previously gained skills, including speech, language, cognitive and motor skills. This is called regression and the early symptoms of this should be considered a medical emergency prompting admission into hospital and full medical, neurological and psychiatric evaluation to ensure any predisposing medical conditions are diagnosed and treated and a comprehensive care plan is promptly started.

Please speak to your medical team to learn more about the signs and symptoms of Kleefstra syndrome.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

Kleefstra syndrome is caused by disease-causing genetic changes (variants) in the EHMT1 gene on chromosome 9. The EHMT1 protein is involved in a process in the cell called histone methylation, which is important for regulating other processes in the body needed for typical development. ⁶ There are typically two types of genetic variants that impact the EHMT1 gene and can cause Kleefstra syndrome:

1. spelling change within the DNA code of the EHMT1 gene (a sequence variant) or
2. loss of part of the chromosome 9, ranging from small missing section within the EHMT1 gene to deletions including EHMT1 gene and other genes on either side of EHMT1 gene

All individuals have a pair of the EHMT1 genes [two copies of the EHMT1 gene] – one on each copy of chromosome 9 inherited from each parent. Kleefstra syndrome is caused by a genetic variant in one of the pair/copy of the EHMT1 genes that results in reduced levels of EHMT1 protein, known as a pathogenic (disease-causing) variant. As Kleefstra syndrome is caused by disease-causing variants affecting only one of the pair of the EHMT1 genes, it is an autosomal dominant condition.

These genetic variants typically occur randomly by chance (de novo) prior to birth and are rarely inherited from their parents.² There has been some reported cases of the genetic variant being inherited from parents who themselves are mildly or not affected, due to somatic mosaicism (the genetic variant is not in all cells) or balanced/reciprocal translocation (the genetic material is still present but on a different chromosome) in the parents. More information about inheritance pattern, mosaicism, and translocations, can be found at:

• Centre for Genetics Education: Autosomal dominant inheritance
• Centre for Genetics Education: Mosaicism
• Centre for Genetics Education: Chromosome changes

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Diagnosis of Kleefstra syndrome may be considered based on clinical features that are considered characteristic of Kleefstra syndrome and confirmed by genetic testing.

More information about clinical characteristics and diagnosis, including when a diagnosis of Kleefstra syndrome should be considered, can be found at GeneReviews^®: Kleefstra Syndrome (under Clinical Characteristics and Diagnosis).

Standard genetic testing may involve chromosomal microarray analysis (CMA) and/or exome/genome sequencing to identify genetic changes in the EHMT1 gene. For some individuals, if there is an uncertain result from genetic testing, further screening for a characteristic ‘episignature’ can be helpful. This is a test which looks at changes in the function of the EHMT1 protein and is available in Australia through certain specialist genomic laboratories, organised by clinical genetics teams. Subsequent genetic testing may be offered to parents even if they appear unaffected, to determine if they carry the genetic change and have an increased chance of passing it on to future children.

General information about these genetic tests can be found at:

• Pathology Tests Explained: Genome-wide chromosome microarray testing
• Pathology Tests Explained: Whole Genome or Whole Exome Testing for Childhood Syndromes

As part of the diagnostic process, doctors may do a differential diagnosis, which is to rule out other conditions that have similar symptoms, such as other genetic conditions with overlapping features of Kleefstra syndrome.

Please speak to your medical team to learn more about the available pathways for diagnosis of Kleefstra syndrome.

There is currently no curative treatment for Kleefstra syndrome. There are many strategies and therapies to support optimal health and wellbeing. A multi-disciplinary team is critical to ensure appropriate care and ongoing support for the person with Kleefstra syndrome and their family. ² It is important to involve a paediatrician (for a child) and a general practitioner who can help coordinate care and support and advocacy.

People with Kleefstra syndrome often benefit from early support from speech and language therapies with augmentative and assistive communication technologies to address and optimise their communication needs.^2,4 Other therapies may include physiotherapy, occupational therapy, early intervention and special education programs or supports. ²

Individuals with Kleefstra syndrome should be evaluated at diagnosis for differences with the structure of their heart (using echocardiogram/heart ultrasound) and kidneys (with a renal ultrasound scan) as well as for hearing and vision, and treated accordingly. ^2,7 People with Kleefstra syndrome are also recommended to have a comprehensive medical assessment at least once a year to check their growth and nutrition, general health, mood, behaviour and sleep, hearing and vision.⁷

A dietitian review can be helpful to ensure balanced nutrition.⁷

Assessment of iron levels, vitamin D, B12 and folate, calcium and other nutritional screening (in the case of feeding difficulties) is recommended every 1-2 years. It is also recommended that thyroid function and bone strength is screened from puberty onset and cardiac rhythm (ECG) from age of 18.⁷

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities. For many rare diseases, treatment options may be limited. Participation in a clinical trial may provide access to new or emerging therapies.

Healthcare professionals involved in the care of individuals with Kleefstra syndrome may include general practitioners (GP), paediatricians, specialist nurses, social workers, clinical geneticists and genetic counsellors, neurologists, cardiologists, ophthalmologists, audiologists, gastroenterologists, urologists, nephrologists, Ear Nose and Throat (ENT) specialists, speech pathologists/therapists, occupational therapists, physiotherapists, psychologists and psychiatrists. ³ The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Virtual clinic:

Gene2Care Kleefstra Syndrome Clinic, The Sydney Children’s Hospital Network (NSW)

This national virtual clinic aims to connect with individuals with Kleefstra syndrome and their parents/cares, provide updates on the latest medical advice and guidelines recommended for medical care, support, as well as information and research opportunities. They have developed a guidebook with families which can be found at Rare Diseases NSW: Resources and guides.

For non-urgent enquiries or appointment please contact the admin team:
Phone: (02) 9382 5607/ 5608/ 5609
Fax: (02) 9382 5683
Email: [email protected]
Care Navigation (clinical nurse specialist) enquiries: [email protected]

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

This may not be applicable to all rare diseases but for many, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

International clinical evidence-based guideline for Kleefstra syndrome developed by an international consortium of 43 clinical experts and patient representatives (including Australian clinicians and family representatives) from 15 countries, published in 2026. The guideline provides recommendations across different areas of clinical management, including genetic testing and counselling, mental health and behaviour, regression, neurology, sleep, vision and hearing, speech-language-communication, cardiology, growth and metabolism, constipation, and parental support.

OrphanAnesthesia has Anaesthesia recommendations for Kleefstra syndrome, updated in 2019.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

In addition, individuals, their parents, families and carers often develop extensive expertise on their specific rare disease. It is important to recognise that they can contribute valuable knowledge about their rare condition. Rare diseases often impact individuals differently, so it’s important to consider a person’s lived experience.

It may be important to consider the following when managing individuals living with Kleefstra syndrome at emergency departments/services:

• Individuals often need support with communication and quiet, calm areas.
• Acute changes in mood and sleep (for example loss of the normal sleep-wake cycle for more than two nights) to be urgently assessed in case of the possibility of regression- prompting full neurological and psychiatric evaluation.
• Individuals are at a higher chance of epilepsy and gastrointestinal complications related to dysmotility.

The Gene2Care Kleefstra Syndrome clinic is a research integrated model of care that aims to improve care for children and their families living with diagnosed or suspected rare genetic conditions. It includes a GeneSTART rare disease registry and GeneAdd undiagnosed disease program.

Australian Organisation:

Kleefstra Kidz
Email: [email protected]
Kleefstra Kidz is a new Australian patient support group for individuals living with Kleefstra syndrome and their families.

International Organisations:

IDefine (Global)
Website: https://www.idefine.org/
IDefine is a nonprofit organization that exists to provide a central community for families affected by Kleefstra Syndrome (KS), including those in Australia. IDefine is committed to identifying life-changing treatments & cures for those with Kleefstra syndrome, a neurodevelopmental disorder caused by a loss of function in one copy of the EHMT1 gene.

Kleefstra Syndrome UK (United Kingdom)

Website: https://www.kleefstrasyndrome.org/
Kleefstra Syndrome UK exists to offer support, education and awareness of this rare condition to families across the world.

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

Kleefstra syndrome varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on Kleefstra syndrome can be found at:

• Centre of Research Excellence Translational Centre for Speech Disorders: Kleefstra syndrome
• Genetic and Rare Diseases (GARD) Information Center: Kleefstra syndrome
• Unique – Understanding Rare Chromosome and Gene Disorders: Kleefstra syndrome

GeneReviews^®: Kleefstra Syndrome

Online Mendelian Inheritance in Man (OMIM)^®: #610253 Kleefstra Syndrome 1; KLEFS1

Orphanet: Kleefstra syndrome

This page has been co-developed by Rare Voices Australia (RVA)’s RARE Portal team in consultation with healthcare professionals from the Gene2Care Kleefstra Syndrome Clinic at Sydney Children’s Hospital – Dr Lisa Ewans, A/Professor Elizabeth Emma Palmer, Carolyn Shalhoub and Eleanor Farley.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.