COL4A1/A2-related disorders, also known as Gould syndrome, includes a spectrum of disorders caused by genetic variants in the COL4A1 or COL4A2 genes.^1,2 These disorders were previously recognised as separate conditions, however it is now recognised that these disorders share overlapping symptoms, and are recognised as part of the COL4A1/2-related disorders.^1,2,5 These disorders include:

• Brain small vessel disease 1 with or without ocular anomalies
• Brain small vessel disease 2
• Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome
• Familial isolated retinal artery tortuosity
• Susceptibility to intracerebral haemorrhage
• Pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL)

COL4A1 and COL4A2 genes provide instructions for making the alpha-1 and alpha-2 chains of type IV collagen, a key component of basement membranes. Basement membranes are specialised structures found throughout the body that provide structural support, regulate filtration in the kidneys, and play important roles in cell signalling.³

Variants in COL4A1 and COL4A2 genes can disrupt the normal function of type IV collagen, affecting basement membranes found in multiple organs and systems. The brain, eyes, muscles, and kidneys are among the most commonly affected organs, although the symptoms and severity can vary widely between individuals.^1,2 The symptoms may also differ among individuals of the same family.

Synonyms: Gould syndrome.²

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:477759 COL4A1 or COL4A2-related cerebral small vessel disease

There is currently no known ICD:11 classification for this group of conditions.

As basement membranes can be found throughout the body, COL4A1/2-related disorders may affect different organs and systems, leading to a wide range of symptoms and severity.^1,2 Depending on the age of onset (infant, childhood or adult), the symptoms may also present differently.⁴

The spectrum of symptoms may include:^1,2,5-7

Please speak to your medical team to learn more about the signs and symptoms of a specific COL4A1/A2-related disorders.

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.

COL4A1/A2-related disorders are genetic conditions caused by genetic changes (variants) in the COL4A1 or COL4A2 gene on chromosome 13.⁸

Everyone has two copies (alleles) of the COL4A1 and COL4A2 genes – one inherited from each parent. Most COL4A1/A2-related disorders are autosomal dominant conditions, which means that a disease-causing variant in just one copy of the COL4A1 or COL4A2 gene can result in the condition.^1,2,8

In most affected individuals, the variant is inherited from an affected parent. In some individuals, the variant occurs randomly (de novo) before birth and is not inherited from either parent.^1,2,5 Whether inherited or de novo, the variant can be passed on to the next generation. A person with an autosomal dominant COL4A1 or COL4A2 variant has a 50% chance of passing the variant to each of their children. More information on autosomal dominant inheritance pattern can be found at Centre for Genetics Education: Autosomal dominant inheritance.

In a small number of individuals, COL4A1/A2-related disorders have been reported to follow an autosomal recessive pattern of inheritance.⁷ In these cases, both copies of the COL4A1 or COL4A2 gene must carry a disease-causing variant for the condition to occur.

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 COL4A1/A2-related disorders may be made based on:^1,2,5

• Family history
• Physical examination
• Imaging of the brain and neck to check for structural or blood vessel abnormalities
• Imaging of the heart to look for abnormalities
• Eye examination
• Genetic testing to look for genetic variants in the COL4A1 or COL4A2 genes

Please speak to your medical team to learn more about the available pathways for diagnosis of COL4A1/A2-related disorders.

There is currently no curative treatment for COL4A1/A2-related disorders. Treatment is targeted at managing symptoms (symptomatic management), regular monitoring, supportive care and involves a multidisciplinary care team. This may include:^1,2,5

• Management of aneurysms and/or additional cerebrovascular (brain blood vessels) risk factors such as high blood pressure, high cholesterol, diabetes, or obesity.
• Management of epilepsy
• Management of visual function
• Management of kidney function
• Physiotherapy and speech therapy

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 COL4A1/A2-related disorders may include general practitioners (GP), neurologists, ophthalmologists, nephrologists, clinical geneticists, genetic counsellors, physiotherapists, and speech pathologists.^1,2 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.

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

We are not aware of any clinical care guidelines for COL4A1/A2-related disorders 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:

• COL4A1 and COL4A2-related disorders: Clinical features, diagnostic guidelines, and management developed by paediatric and adult medical specialists with expertise in COL4A1-COL4A2 related disorders, published in 2025.

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.

Australian Organisation:
We are not aware of any rare disease organisations for COL4A1/A2-related disorders in Australia. If you are aware of any relevant Australian organisations, please let us know via the Contribute page.

International Organisation:
The Gould Syndrome Foundation (United States of America)
Website: https://www.gouldsyndromefoundation.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.

COL4A1/A2-related disorders vary between individuals, and each person’s experience is unique.

The Gould Syndrome Foundation: Personal Stories has personal stories of individuals living with COL4A1/A2-related disorders.

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 COL4A1/A2-related disorders can be found at:

• National Organization for Rare Disorders (NORD): COL4A1/A2-Related Disorders

GeneReviews®: COL4A1-Related Disorders

Online Mendelian Inheritance in Man, OMIM^®:#175780 Brain small vessel disease 1 with or without ocular anomalies; BSVD1

Online Mendelian Inheritance in Man, OMIM®:# 614483 Brain small vessel disease 2a, autosomal dominant; BSVD2A

Online Mendelian Inheritance in Man, OMIM®:#180000 Retinal arteries, tortuosity of; RATOR

Online Mendelian Inheritance in Man, OMIM®:# 611773 Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps; HANAC

Online Mendelian Inheritance in Man, OMIM®:#614519 Hemorrhage, intracerebral, susceptibility to; ICH

Online Mendelian Inheritance in Man, OMIM®:#618564 Microangiopathy and leukoencephalopathy, pontine, autosomal dominant; PADMAL

Orphanet: COL4A1 or COL4A2-related cerebral small vessel disease

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.