Tubulinopathies is a group of genetic, neurodevelopmental conditions characterised with brain malformations.^1-6 These conditions are caused by genetic changes in genes that code for tubulin proteins, such as TUBA1A, TUBB, TUBB2A, TUBB2B, TUBB3, TUBB4A, and TUBG1 genes.¹ Tubulins are the building blocks of microtubules (narrow, hollow tubes inside a cell) which are responsible for structural support, division and movement of cells in the body.² Microtubules play a critical role in prenatal brain development by regulating neuron’s growth, migration to specific parts of the brain, maturation and function.^2,3

Genetic variants in tubulin genes affect the development and function of the brain, leading to a range of symptoms, such as epilepsy, motor and cognitive (thinking) impairments.^1,3 Tubulinopathies can be categorised based on the affected tubulin gene. Different genetic variants may cause distinct pattern of brain abnormalities and other symptoms.^1,3

Synonyms: Tubulin-related cortical dysgenesis.¹

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.

There is no known ORPHAcode or ICD-11 classification.

The symptoms and severity of tubulinopathies can vary between individuals with different genetic variants as well as between those with the same genetic variants.^3,6

Common symptoms of tubulinopathies include:^1-6

• brain abnormalities such as:
  • structural differences in different parts of the brain, such as the corpus callosum, cerebellum, brain stem, basal ganglia
  • abnormal folding pattern of the brain’s surface. The brain surface normally has many ridges and grooves to increase its surface area. Common folding patterns in individuals with tubulinopathy include lissencephaly (total loss of folding patterns, also known as “smooth brain”), pachygyria (reduced folding with broader ridges and shallower grooves) or polymicrogyria (too many ridges, and the ridges are unusually small).
  • smaller brain size
• cognitive (thinking) impairment, developmental delay, and intellectual disability
• motor impairment such as lack of motor control, spasticity (abnormal muscle stiffness) or inability to walk
• epilepsy and/or seizures
• delayed speech or do not develop speech
• facial diplegia (paralysis or weakness affecting both sides of the face)
• abnormal eye movements such as strabismus (when both eyes do not align in the same direction, also known as “crossed eyes”)

Please speak to your medical team to learn more about the symptoms and health implications of a specific type of tubulinopathy.

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.

Tubulinopathies are genetic conditions. These conditions are caused by disease-causing genetic changes (variants) in genes that code for tubulin proteins. These genes are TUBA1A, TUBB, TUBB2A, TUBB2B, TUBB3, TUBB4A, and TUBG1.^4-6

Most tubulinopathies are autosomal dominant conditions, which means that having genetic variant in just one copy of the gene can cause tubulinopathy.^1,3 The genetic variant can be inherited, which means it can be passed on to the next generation. If a parent has the autosomal dominant gene variant, there is a 50% chance that they will pass that genetic variant to each of their children. More information on autosomal dominant inheritance pattern can be found at Centre for Genetics Education: Autosomal dominant inheritance.

Most tubulinopathies occur randomly (de novo) prior to birth and is not passed down (inherited) from their parents.¹ In rare cases, the genetic variant was inherited from a parent who has the genetic variant in some but not all of their cells (this is called mosaicism). The parent may be mildly  or 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 tubulinopathies may be made based on:^1,3

• Family history
• Physical examination
• MRI scans of the brain
• Genetic testing looking for genetic variants in TUBA1A, TUBB2A, TUBB2B, TUBB3, TUBB, TUBB4A, TUBG1 genes

Please speak to your medical team to learn more about the available pathways for diagnosis of a specific type of tubulinopathy.

There is currently no curative treatment for tubulinopathies. Treatment is targeted at managing symptoms and supportive care. This may include:¹

• Management of seizures
• Physiotherapy
• Occupational therapy
• Vision therapy
• Speech therapy
• Nutritional management such as tube feedings may be needed

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 tubulinopathies may include general practitioners (GP), paediatricians, neurologists, epilepsy specialists, physiotherapists, speech pathologists, ophthalmologists, genetic counsellors and others.¹ 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 tubulinopathies in Australia or internationally If you know of any relevant care guidelines, please let us know via the Contribute page.

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.

Tubulin Biobank is a group of researchers from across the globe that are dedicated to understanding the tubulinopathies.

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 tubulinopathies as a whole in Australia or internationally. If you are aware of any relevant organisations, 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) 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.

The following international organisation provides support to a specific type of tubulinopathy:
TUBB3 Foundation (United States of America)
Website: https://tubb3foundation.org/

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.

Tubulinopathies vary 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 tubulinopathies or a specific type of tubulinopathy can be found at:

• Unique: TUBA1A-associated tubulinopathy

GeneReviews®: Tubulinopathies Overview

Online Mendelian Inheritance in Man, OMIM®:#611603 Lissencephaly 3; LIS3

Online Mendelian Inheritance in Man, OMIM®:#614039 Cortical dysplasia, complex, with other brain malformations 1; CDCBM1

Online Mendelian Inheritance in Man, OMIM®:#615412 Cortical dysplasia, complex, with other brain malformations 4; CDCBM4

Online Mendelian Inheritance in Man, OMIM®:#615763 Cortical dysplasia, complex, with other brain malformations 5; CDCBM5

Online Mendelian Inheritance in Man, OMIM®:#6015771 Cortical dysplasia, complex, with other brain malformations 6; CDCBM6

Online Mendelian Inheritance in Man, OMIM®:#610031 Cortical dysplasia, complex, with other brain malformations 7; CDCBM7

Human Phenotype Ontology (HPO): Tubulinopathy-associated dysgyria

This page is 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.