What Is Gottron Syndrome?

Overview

Gottron syndrome is a rare inherited disorder and a type of dermatomyositis.¹ Dermatomyositis is an idiopathic autoimmune inflammatory disorder, which means it is a randomly developed inflammatory disorder where the immune system attacks the body's own cells by mistake.³ Gottron syndrome is identified as premature ageing, and it can be detected from birth and childhood.1 This disorder is a non-progressive syndrome that affects distal extremities, which are body parts furthest away from the centre of the body.² It often affects the skin on the hands and feet, making it thin and fragile. This can also be referred to as skin atrophy. Typically, this is caused by a loss or reduced fatty tissue found under the skin.¹ This may lead to hollow cheeks and a pinched face.¹ Furthermore, it may also cause slow growth.⁴ Gottron syndrome is a genetic disorder; therefore, it can be inherited from parents. It can be inherited through autosomal dominant or autosomal recessive inheritance. This means a child can have the disorder if they have an affected parent or two carrier parents.¹ To diagnose gottron syndrome, doctors will clinically analyse a patient to identify any symptoms that align with gottron syndrome. Due to the genetic component of this disorder, clinicians may also perform genetic testing on the patient and their parents to identify any other associated genes that may be an underlying cause.¹ Other tests, such as biopsies and blood tests for autoantibodies, may also be used to aid diagnosis.² Usually, a variety of treatments are used to treat each of the clinical features and it may also vary depending on the underlying cause as well.⁹

Signs and symptoms

The clinical presentation of Gottron syndrome is complex and can appear slightly different across individuals. However, most signs and symptoms are recognisable from as early as birth and early childhood.¹ The most identifiable signs include:¹

• Older appearance
• Thin and fragile skin on extremities
• Hollow cheeks
• Pinched face
• Reduce the amount of fat under the skin (subcutaneous fat)
• More visible veins
• Skin discoloration
• Prone to bruising
• Cranial development defects
• Skeletal defects
• Slow growth
• Red spots and patches on elbows and knees⁶
• Heliotrope rash on eyelids⁶
• Violaceous scaling papules on nail folds and joints⁶
• Dermatomyositis on scalp⁶
• Muscle weakness⁷

If you notice any of these symptoms or signs in yourself or your child it is best to consult a doctor who will be able to perform a variety of diagnostic tests and confirm whether these symptoms are due to gottron syndrome. 

Underlying causes

Gottron syndrome has a very complex nature; therefore, it is to identify just one underlying cause. There are three main underlying causes of Gottron syndrome. These are genetic predispositions, environmental triggers and autoimmune-related causes.²

Genetic

Genes are commonly an underlying cause in many diseases. Gottron syndrome is a genetic syndrome where there are a few mutations that are associated with its prevalence.² A mutation is a change in DNA sequence. This sequence acts as a code that cells use to make the right type of proteins that eventually form cells and tissues.⁵ If this sequence is altered, the incorrect protein will be made. Alternatively, no protein might be made, which may cause severe complications. Some mutations have no impact on overall health, whereas others can be significant and result in severe and rare diseases. The three main mutated genes that are associated with Gottron syndrome are LMNA, ZMPSTE24, and COL3A1. This disorder can be caused by autosomal dominant inheritance and autosomal recessive inheritance. Dominant inheritance means only one copy of a gene from one parent is needed to cause the disorder, whereas recessive needs two copies of the gene, one from each parent.¹ If they only have one recessive gene, the child will be a carrier and not display symptoms of Gottron syndrome.¹

Autoimmune

Research suggests that there is also an autoimmune component to Gottron syndrome. An autoimmune disease is where the body attacks its own cells and tissues. In this instance, the body produces an inappropriate immune response, resulting in an inflammatory response. This affects the blood vessels and skin, manifesting clinical features associated with Gottron syndrome.⁸  Many autoimmune diseases have autoantibodies that are linked to the symptoms of the disease. For example, anti-Jo-1 is one of the most common antibodies present.² This antibody targets histidyl-tRNA synthetase and is linked to fever and inflammatory arthritis.^.2 There are lots of other antibodies associated with Gottron syndrome, including anti-MDA5, anti-PL-7, anti-Mi-2, and anti-P140.²

Environmental triggers

There are many environmental triggers that may result in Gottron syndrome. Viruses such as HIV, parvovirus, and echovirus have also been suggested to trigger Gottron syndrome.⁸ Usually, these triggers would need to be present alongside a genetic predisposition. A genetic predisposition is where you have the genes that make you more likely to develop a disease, especially when triggered by an environmental factor. When a virus enters the body, its presence can cause an abnormal immune response. This inappropriate immune response causes the body’s own antibodies to attack the body's own tissues and cells.⁸ As Gottron syndrome is very complex, there are many other environmental factors that may also contribute to Gottron syndrome, such as cancer tumours, vaccinations, certain medications, breast injections, and collagen injections.⁸

Diagnosis

Gottron syndrome, also known as acrogeria, is extremely rare. By 2022, only 50 cases will have been reported in medical literature. This highlights how rare this condition is and that there is very little prevalence.² Gottron syndrome is diagnosed by a healthcare professional or doctor when performing a comprehensive clinical examination. A clinical examination is needed to identify key symptoms that align with the criteria for Gottron syndrome. In addition to this, biopsies may be used to confirm this diagnosis. After this diagnosis, further testing may be used to help identify the underlying cause.¹ This may include genetic testing as Grotton syndrome has a genetic component.¹ Also, blood tests looking for the antibodies anti-MDA5 and anti-Jo-1 may be used.² These antibodies are tested for because they are affected by the autoimmune response associated with Gottron syndrome.²

Management and treatment

Gottron syndrome uses a variety of treatments as different treatments are needed for different clinical features of the disease.³ These treatments include 

• High-dose oral corticosteroids
• Immunosuppressants
• Topical corticosteroids
• Intravenous immunoglobulins

There are also other ways to treat the symptoms associated with Gottron syndrome. This includes managing muscle weakness with physiotherapy and protecting the skin from UV rays using sun protection.⁹ The earlier Gottron syndrome is diagnosed; the better the treatment outcome will be.⁹ A doctor or healthcare professional will be able to diagnose and create an adequate treatment plan designed for each person's individual needs.

Prognosis and complications

Gottron's syndrome is a complex disorder and has various aspects and features that impact a person's well-being. These implications include muscle diseases characterised by muscle weakness and fatigue.⁹ These symptoms can lead to a reduction in a person's daily activity and, therefore, reduce their quality of life. The most common way to identify Gottron syndrome is through the clinical features presented on the skin of the hands and feet. However, skin changes may also be noticed on joint and nail beds.9 A more serious complication associated with Gottron syndrome is lung disease. This association highlights how significant the effects of Gottron syndrome can be across the whole body.9 In order to intervene as early as possible, regular medical check-ups are used to identify any complications that may need treatment.⁹ Early intervention is crucial for decreasing the severity of the complication and improving prognosis. Other manifestations include oesophagal disease, fevers, weight loss and fatigue.⁹ 

Summary

Gottron syndrome is a type of dermatomyositis, and it is very uncommon. It is a genetic disorder that has a variety of clinical presentations. The most identifiable feature of Gottron syndrome is premature ageing. This is presented as thin, fragile skin mostly on the hands and feet. Gottron syndrome is non-progressive. It can be caused through autosomal dominant or recessive inheritance. As well as a genetic predisposition, environmental triggers and autoimmune factors are also the underlying cause of Gottron syndrome. Environmental factors include cancerous tumours, viruses, and certain medications. Furthermore, the autoimmune component triggers an inflammatory response. This response is where an inappropriate immune response starts to attack the body’s own tissues and cells. The diagnosis of Gottron syndrome is conducted by a medical professional who will use a variety of diagnostic tools. Thai includes genetic testing, biopsies, blood tests and clinical observation. Following this diagnosis, a range of different treatments can be put into place to manage the disease. These treatments are designed to target each clinical feature of the disorder. These treatments range from corticosteroids, immunosuppressants, and physiotherapy. Another method is using sun protection to protect the skin from any further damage from UV rays. It is very important to detect Gottron syndrome, as the earlier the diagnosis, the better the treatment outcome and the reduced risk of complications developing. Some manifestations include muscle diseases, skin diseases, and lung diseases. Early intervention offers a better quality of life and a holistic care plan for those affected.