Dystonia that is detected in childhood can progress rapidly and interfere in the development of the child's language and mobility, causing a physical disability that will affect them throughout life.

Causes

Dystonia is a very heterogeneous disease, which can occur for a variety of reasons:

• Genetics. Dystonia caused by a defect in a gene. Most genetic forms of dystonia appear in childhood and adolescence. Currently, over 200 genes that cause dystonia have been found. Among the different types of genetic dystonia there are:
  • Recessive hereditary dystonia: Dystonia caused by congenital errors in metabolism or a failure in the production of certain enzymes.
  • Dominant hereditary dystonia: Most isolated forms of dystonia belong to this category, classified according to DYT nomenclature. Myoclonic dystonia is an example. In this case, more than 80% of cases are inherited from the father.
  • De-novo dominant dystonia: These are severe forms of the disease, such as those caused by mutations in the GNAO1 gene, so transmission to offspring is difficult.
  • Mitochondrial hereditary dystonia: These are progressive forms of dystonia that can have very variable degrees of severity. Children with this type of dystonia suffer from a disease called Leigh syndrome: A defect in mitochondrial metabolism that causes the brain not to generate enough energy to function properly and injuries occur in the ganglia of the base.
  • Dystonia linked to the X chromosome: Some examples are dystonia-parkinsonism, also called DYT3 or deafness-dystonia syndrome.
• Degenerative. They also occur due to a defect in a gene but, unlike the previous ones, they produce lesions of progressive character in the central nervous system.
• Idiopathic. Here, there is no genetic cause or event that has been found to cause a lesion in the nervous system.
• Acquired. In this case, the cause is related to damage to the central nervous system due to a lack of oxygen during pregnancy or childbirth, brain trauma or exposure to toxic elements.

Due to its incidence, dystonia is considered a rare disease.

Symptoms

Dystonia in childhood can occur in isolation or associated with other neurological and development problems. It can cause difficulty in everyday tasks such as walking, speaking, feeding oneself and taking care of personal hygiene.

When presented in isolation it is called primary dystonia and often has a genetic origin. Children who suffer from it do not usually have other health problems and their neurological development is normal. At first it manifests itself in actions such as walking, running, or writing and, later, can spread to other parts of the body and cause widespread dystonia.

Myoclonic dystonia is one of the most frequent hereditary forms of dystonia in childhood. It is characterised by the presence of sustained (dystonic) and abrupt (myoclonic) muscle contractions and psychiatric disorders such as anxiety, depression and obsessive-compulsive features. The first symptoms appear in childhood and affect the lower limbs of children, who have difficulties walking, running and with sports. This disease also affects the social relationships of these children, who have problems speaking in public or eating and drinking with friends.

Dystonia can also be associated with other neurological problems, such as spasticity, ataxia, weakness, delay in neurological development and intellectual disability. In this case we call it secondary dystonia and it is necessary to rule out neurometabolic and neurodegenerative causes.

Who is affected by the condition?

It affects children, adolescents, and adults of all ages.

Diagnosis

First of all, patients are subjected to a series of clinical, metabolic, neurophysiological and neuroimaging studies to classify the type of dystonia, before carrying out genetic studies. In patients with myoclonic dystonia, first of all, a Sanger sequencing study is carried out to determine the gene that causes it, and in the other patients, a complete family exome sequencing(parents and patient) is carried out or the index case (patient) based on the DNA samples available.

Being a rare and very heterogeneous disease it is difficult to reach a correct diagnosis and treatment plan. It is important to distinguish hereditary dystonia from childhood cerebral palsy, caused by brain damage at birth, since its diagnosis has very important consequences for treating the disease later.

A diagnosis in time decreases the need to carry out more diagnostic tests, making it possible to form a prognosis and to advise families on avoiding future diseases. It also has a very positive psychosocial impact on the patient and family. And most importantly, an exact diagnosis of the cause that generates the dystonia makes it possible to guide the best possible treatment for each patient, in what we call personalised medicine.

Typical treatment

Dystonia in childhood is progressive and debilitating, but can be prevented with early diagnosis and the use of specific therapies depending on the identified genetic defect.

Levodopa is the treatment of choice in dopa-sensitive dystonia, caused by a defect in the synthesis of dopamine. Botulinum toxin is used to control focal dystonia. In the case of widespread dystonia, different drugs are used to decrease tremors, muscle tone, and painful spasms. And in some cases of paroxysmal dystonia, which is characterised by brief and repetitive involuntary movements during the night, antiepileptic drugs are used.

Surgical alternatives

An intrathecal baclofen pump administers liquid medication through a device that is placed under the skin, and is used to treat generalised secondary forms of dystonia. It reduces pain, decreases muscle tone and spasms. It is a treatment we call symptomatic and palliative, since it does not improve the motor function of the patient.

Deep brain stimulation or globus pallidus stimulation, two electrodes are placed in the globus pallidus using a stereotaxic technique, it is the treatment of choice in primary dystonia, especially if they are widespread and do not respond to conventional medication. In these cases children can recover the function of the area affected by dystonia and improve their quality of life. It can also be useful in patients with secondary forms of dystonia, although its effectiveness is less than in primary forms of dystonia.

Prevention

Performing genetic testing is the best prevention to avoid having more children affected by this disease in the same family.

Hereditary metabolic diseases (HMD) are chronic progressive multi-system illnesses that may appear at any age and that in most cases pose diagnostic and therapeutic challenges. Our Unit has been recognised as a leader within Spain (CSUR) and Europe (ERN) for this pathology and takes part in the neonatal screening programme in Catalonia. We are the only centre in Catalonia to offer complete care from paediatrics to adults with particular expertise in lysosomal storage disorders.

HMDs are divided into:

- Intermediary metabolism HMD: usually with acute symptoms.

- HMD related to the organelles (lysosomal storage disorders, peroxisomal diseases, mitochondrial disorders and endoplasmic reticulum storage diseases): chronic presentation with no decompensations (with the exception of some mitochondrial disorders)

Multiple systems in the body are affected and different organs and systems are involved with varying symptoms depending on the disorder and the patient’s age. These disorders require a coordinated approach to care and programmes to manage the transition to adulthood. 

Symptoms

Many symptoms become evident during childhood in the form of delayed physical growth and delayed psychomotor development. There may be associated heart problems, kidney conditions, and at times decompensations leading to liver or kidney failure and neurological impairment. In the case of organelle disorders, symptoms are chronic and affect the bones and organs of the senses in greater measure. They are more common in adults than intermediary metabolism disorders.   

Diagnosis

Diagnosis is carried out by:

• Laboratory tests: biochemical and enzyme analysis on different tissues according to the suspected diagnosis.
• Specific genetic testing to confirm diagnosis

Treatment 

They are chronic disorders that need to be treated in specialised centres with multidisciplinary teams to provide support for all related health problems.

The following may be necessary, depending on the type of disorder:

• A special and complex diet with different supplements and cofactors
• Pharmaceuticals that help avoid build up of toxic substrates
• Highly complex medication such as enzyme replacement therapy or substrate inhibitors
• Stem cell, liver or kidney transplant 

Prevention

Prevention consists of thorough genetic and reproductive counselling if there is a family history of the disease. Early diagnosis of some diseases through the neonatal screening programme enables effective treatment and improved prognosis.