Baraitser-Winter cerebrofrontofacial syndrome (BWCFF) is a genetic, developmental disorder that is present from birth (congenital).¹ It affects many parts of the body, particularly the brain and face. BWCFF is characterised by distinctive facial features, brain abnormalities, and intellectual disability.^1,2

BWCFF is caused by genetic changes (variants) in the ACTB or ACTG1 gene.^3,4,5 This leads to impaired neuronal migration, a process in which nerve cells (neurons) move to their proper positions in the developing brain, which affects brain development and function.²

Synonyms: Baraitser-Winter syndrome, Cerebrooculofacial lymphatic syndrome, COFL syndrome, Fryns-Aftimos syndrome (pachygyria, mental retardation, epilepsy, and characteristic facies), BRWS, BWCFF.^5,6

Baraitser–Winter malformation syndrome, Fryns–Aftimos syndrome and cerebrofrontofacial syndrome types 1 and 3 were previously thought to be different conditions. With the advancement of research, it is discovered that these conditions are caused by changes in the same genes (ACTB or ACTG1 genes). The term Baraitser-Winter cerebrofrontofacial syndrome has been proposed to represent these conditions.⁷

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:2995 Baraitser-Winter cerebrofrontofacial syndrome

There is no known ICD-11 classification.

ICD-10: Q87.0

The symptoms and severity of BWCFF vary widely between individuals.¹

Symptoms of BWCFF may include but not limited to:^1,2,6-9

• distinctive facial and skull features such as widely spaced eyes, drooping eye lid, big and round nose with broad nose bridge, arched eyebrow, visible ridge running down the centre of the forehead (metopic ridge), long philtrum (vertical groove between the base of the nose to the upper lip), wide mouth, and progressive coarsening of facial features.
• brain abnormalities such as:
  • pachygyria often occurs in the frontal areas of the brain. The brain surface normally has many folds and grooves, but in pachygyria, there are abnormally few and thick folds, which affect brain functions. A more severe condition, lissencephaly (where normal brain folds fail to form and the brain surface appears unusually smooth), has also been reported, but is less common.
  • abnormalities in the corpus callosum (thick bundle of nerve fibres that connect the left and right brain for transfer of information and communication).
• intellectual disability ranging from mild to severe
• developmental delay and learning difficulties
• seizures and/or epilepsy
• coloboma of the eye (missing tissue in a part of the eye, such as the iris, retina or eye nerve) which can lead to vision problems
• joints stiffness, muscles wasting and weakness, which tends to worsen over time and can affect walking
• hypotonia (low muscle tone) and spasticity (stiffness) of the lower limbs
• short stature
• abnormalities of the heart and kidney
• problems with the gastrointestinal system such as chronic constipation, reflux, feeding difficulties, frequent vomiting, and diarrhea
• hearing loss

BWCFF caused by variants in the ACTB gene have been associated with more severe facial and skull features, while BWCFF caused by variants in the ACTG1 gene have been associated with more severe brain abnormalities.^1,9

Please speak to your medical team to learn more about the symptoms and health implications of BWCFF.

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.

BWCFF is a genetic condition caused by disease-causing genetic changes (variants) in the ACTB gene on chromosome 7 or ACTG1 gene on chromosome 17.^6,8 These genes produce components of a protein called actin, which is essential for many functions in cells. Actin plays an important role in brain development to guide neuronal migration.^1,2,6,9

All individuals have two copies (alleles) of the ACTB or ACTG1 gene – one on each chromosome that is inherited from each parent. BWCFF is an autosomal dominant disorder, which means that having a genetic variant in just one of the gene copies can result in this condition.⁶ More information on autosomal dominant inheritance pattern can be found at Centre for Genetics Education: Autosomal dominant inheritance factsheet.

For most individuals with BWCFF, their genetic variants occurs randomly (de novo) prior to birth and is not passed down (inherited) from their parents. In rare cases, the genetic variants were inherited from:⁶

• an affected parent, or
• a parent who has the genetic variant in some but not all of their cells (this is called genetic mosaicism). The parent may be minimally affected. More information on genetic mosaicism can be found at Centre for Genetics Education: Mosaicism.

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 BWCFF may be made based on:^1,6

• physical examination of distinctive facial and skull features
• brain imaging such as MRI scans
• genetic testing to look for variants in ACTB or ACTG1 gene

As part of the diagnostic process, doctors may do a differential diagnosis, where they rule out other conditions that have similar symptoms, such as Noonan syndrome, Kabuki syndrome, Aarskog-Scott syndrome, Escobar syndrome, Teebi hypertelorism syndrome and SERAC1 deficiency.^1,6

Please speak to your medical team to learn more about the available diagnostic pathways for BWCFF.

There is currently no curative treatment for BWCFF. Treatment is targeted at managing symptoms (symptomatic management) and involves a multidisciplinary care team. This may include:^1,6

• management of seizures and/or epilepsy
• management of problems with the vision, hearing, heart, kidney and gastrointestinal system
• physiotherapy, occupational therapy and use of assistive mobility devices (such as wheelchairs, walkers, bath chairs, orthotics, adaptive strollers)
• feeding therapy
• special education
• speech pathology and use of alternative means of communication (such as augmentative and alternative communication [AAC])

Individuals may be monitored for their developmental progress, seizures, vision, hearing, heart, kidney, bones and gastrointestinal health.⁶

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.

Healthcare professionals involved in the care of individuals with BWCFF may include general practitioners (GP), paediatricians, neurologists, ophthalmologists, audiologists, gastroenterologists, cardiologists, nephrologists, geneticists, genetic counsellors, orthopaedists, physiotherapists, occupational therapists, speech pathologists.⁶ The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

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.

For many rare diseases, 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

We are not aware of any clinical care guidelines for BWCFF in Australia. If you know of any relevant care guidelines, please let us know via the Contribute page.

The following guidance is available from international experts outside Australia; however, there may be information that is not relevant or applicable to the Australian context, and may not be up to date:

GeneReviews®: Baraitser-Winter Cerebrofrontofacial Syndrome includes recommendations for evaluation, management, and surveillance for individuals with BWCFF, updated in 2022.

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.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries. For more information, please visit the RARE Portal’s Considerations for Participating in Health and Medical Research page.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in research, including clinical trials,  with your medical team to determine suitability and eligibility.

We are not aware of any rare disease organisations for BWCFF in Australia or internationally. If you know of any relevant organisation, please let us know via the Contribute page. If you are interested in starting an Australian organisation, please see Engaged, Ethical and Effective: A Guide for Rare Disease Organisation Leaders in Australia.

Genetics Alliance Australia (GAA) and Syndromes Without A Name (SWAN) Australia may be able to provide some support for families and individuals affected by an undiagnosed or rare genetic condition for which there is no disease specific organisation in Australia.

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.

BWCFF 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 BWCFF can be found at:

• Genetic and Rare Diseases (GARD) Information Center: Baraitser-Winter syndrome
• Unique: Baraitser-Winter (BWCFF) syndrome

GeneReviews®: Baraitser-Winter Cerebrofrontofacial Syndrome

Online Mendelian Inheritance in Man, OMIM^®:#243310 Baraitser-Winter syndrome 1; BRWS1

Online Mendelian Inheritance in Man, OMIM^®:#614583 Baraitser-Winter syndrome 2; BRWS2

Orphanet: Baraitser-Winter cerebrofrontofacial syndrome

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team.

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.