Condition AZ: m

Background

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Please see below for reliable medical information on myelodysplastic syndrome produced by alternative providers.

NHS website
www.nhs.uk/conditions

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Is there support?

MDS UK Patient Support Group

Tel: 020 7733 7558
Email: info@mdspatientsupport.org.uk
Website: mdspatientsupport.org.uk

The MDS UK Paient Support Group is a Registered Charity in England and Wales no.1145214. The group provides support to all those affected by myelodysplastic syndromes. They provide information and advice, a network of support groups and a networking service. They also aim to raise awareness and organise patient information meetings.

Group details reviewed December 2020.

Background

Mitochondrial diseases  are a group of disorders that are extremely variable in the way people are affected. They occur when the mitochondria, the energy-producing structures found in nearly every cell in the body, do not work correctly. There are many different types of mitochondrial disease. An affected individual can experience problems related to their condition soon after birth or may only develop problems in late adulthood.

There are specialist NHS clinics for rare mitochondrial disorders of adults and children in three centres – Newcastle, London and Oxford.

Credits

Last updated August 2017 by Lyndsey Craven and Sir Doug Turnbull, Wellcome Centre for Mitochondrial Research, Newcastle University, UK.

Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information is provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

What are the symptoms?

Mitochondria are present in nearly every single cell and as a result, any tissue or organ can be involved. Tissues that use a lot of energy, particularly the brain, muscle and heart, are more commonly involved. Some people may have relatively mild symptoms and some people may be more severely affected.

Symptoms can include:

What are the causes?

These conditions are all caused when mitochondria don’t function properly. Mitochondria are often referred to as the ‘powerhouses’ of the cell as their main role is to convert food into energy in the form of adenosine triphosphate (ATP). The mitochondria may be damaged by inherited problems or problems acquired during life. Genetic or inherited mitochondrial diseases occur because of genetic changes in DNA (mutations). These can be inherited in different ways depending on the particular condition. It also depends on whether the genetic change is found in the DNA within the nucleus (nuclear DNA) or the small piece of DNA within the mitochondria (mitochondrial DNA).

How is it diagnosed?

There is no consistent means of diagnosis. It is sometimes possible to make a diagnosis by performing genetic tests on a blood or urine sample. In some cases, a muscle biopsy (removing a small piece of muscle tissue for analysis) is helpful.

How is it treated?

Treatment is targeted at relieving symptoms and delaying the progression of the condition. There is no cure at present but research into new treatments is ongoing. 

Treatment may involve medication, vitamin, and mineral supplements. Some patients respond to certain vitamins, including ubiquinone. Supportive treatments such as physiotherapy and occupational therapy may also be useful. Symptomatic treatment for specific tissue involvement is important.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
This is particularly complicated for mitochondrial diseases because the genetic instructions needed to make mitochondria are found in both the nuclear DNA and the mitochondrial DNA. Genetic changes in the nuclear DNA can be transmitted by either the mother or the father, whilst genetic changes in the mitochondrial DNA are only transmitted by the mother. Thus, the inheritance pattern of mitochondrial disease will depend upon whether the genetic change is found in the nuclear or mitochondrial DNA.

Prenatal diagnosis
Genetic counselling for mitochondrial diseases is difficult but very important for families. The advice will vary depending on the genetic change that has been identified. Prenatal diagnosis is available for couples who are at risk of having a child affected by mitochondrial disease but will not be suitable for all. Other reproductive options include in vitro fertilisation (IVF)-based techniques, such as preimplantation genetic diagnosis (PGD) and mitochondrial donation, which was recently approved for clinical use in the UK.

Is there support?

The Lily Foundation

Tel: 0300 400 1234
Email: liz@thelilyfoundation.org.uk
Website: thelilyfoundation.org.uk

The Foundation is a Registered Charity no.1122071. They provide information and support for children with mitochondrial diseases. They also fund and promote research and aim to raise awareness of mitochondrial diseases.

Group details added August 2017.

Information and support in the UK for children with mitochondrial diseases and related disorders is provided by Climb (see entry Inherited Metabolic diseases).

Information on support in the UK for adults with mitochondrial myopathies and related disorders is provided by the Muscular Dystrophy UK (see entry Congenital Muscular Dystrophy).

Also known as: Centronuclear Myopathy

Background

The myotubular or centronuclear myopathies (CNMs) are a group of rare inherited neuromuscular diseases. There are three forms, each with distinct inheritance patterns:

The CNMs are a subgroup of the congenital myopathies – which means there is muscle weakness and wasting usually present at birth. In addition to weakness of the voluntary muscles, in most forms of CNM there is also weakness of the muscles controlling eye movements, and variable involvement of the muscles involved in swallowing and breathing. Contractures (stiffness) of the joints and deformities of the spine are also relatively common.

Credits

Last updated June 2015 by Dr H Jungbluth, Consultant Paediatric Neurologist, Evelina Children’s Hospital, London, UK.

What are the symptoms?

X-linked myotubular myopathy (XLMTM)

This is one of the more common types of CNM and the most severe. Due to its specific inheritance pattern the condition almost always affects boys. At birth, the symptoms include hypotonia (floppiness), breathing and swallowing difficulties. Motor skills are the most affected, causing difficulties with sitting, standing and walking. The muscles controlling eye movements are almost always affected, but problems with eye movement may not begin until later in life. Some people may need to use a ventilator to breathe. Difficulties with feeding often result in the need for a feeding tube inserted into the stomach. Sadly this condition may mean a reduced life-expectancy for the child, mainly depending on the degree of breathing difficulties.

Autosomal recessive CMN (ar-CNM)

ar-CNM usually occurs in infancy or early childhood. Symptoms include hypotonia, breathing and swallowing difficulties. There is usually weakness of the muscles closest to the trunk of the body, known as the proximal muscles. Weakness of the face muscles may occur, including droopiness of the eyelids and abnormalities of eye movements. Some children may have problems with feeding, and may require breathing support.

Autosomal dominant CNM (ad-CNM)

ad-CNM is generally not as severe as the X-linked or the autosomal-recessive forms. Symptoms develop slowly from birth until well into adulthood. Many affected people are able to walk well into adulthood, but may find themselves in a wheelchair in later life.

What are the causes?

Genes causing all forms of the condition have now been identified:

  • X-linked myotubular myopathy (XLMTM) – myotubularin (MTM1) gene
  • Autosomal-recessive CNM – skeletal muscle ryanodine receptor (RYR1) gene, amphysin II (BIN1)gene and titin (TTN) gene
  • Autosomal-dominant CNM – dynamin 2 (DNM2) gene and, rarely, amphysin II (BIN1) gene.

It is thought that further genes that cause CNM will be identified in time, as not everyone affected by the condition has a change in one of the known genes.

How is it diagnosed?

A diagnosis of CNMs can be made by taking a piece of muscle (a muscle biopsy) and looking at this under a microscope. Genetic testing may be undertaken to look for a mutation in the MTM1, RYR1, BIN1, DNM2 and TTN genes.

How is it treated?

There are supportive measures which can improve the quality of life. In particular, regular physiotherapy and non-strenuous exercise may help maintaining joint range and mobility. Nasogastric or feeding gastrostomy tubes are advised if normal feeding is difficult. Individuals who have problems with their breathing may have to use non-invasive ventilation, particularly at night. The use of antibiotics to treat chest infections and prophylactic immunisations (for example, against flu) are advised. There is no cure for CNMs at the moment, but research is currently ongoing to identify potential therapies.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
CNMs can be inherited in an X-linked recessive, autosomal-recessive and autosomal dominant manner. Affected families should be referred to a genetics centre for information and support.

Prenatal diagnosis
Prenatal diagnosis is possible if the mutation causing the CNM in an affected family has been identified.

Is there support?

The Myotubular Trust

Email: via website
Website: https://myotubulartrust.org/

The trust is a Registered Charity in England Wales no. 1137177. They provide information and support to anyone affected by centronuclear and myotubular myopathy. They also raise awareness and fund and promote research.

Group details added June 2021.

Background

The main characteristics of megalencephaly-capillary malformation (MCAP) syndrome are megalencephaly (large brain size) and a marbled appearance of the skin (called cutis marmorata), which is present at birth and is due to problem with small blood vessels called capillaries.

Credits

Medical text written February 2002 by Dr Jill Clayton-Smith. Last updated December 2012 by Professor Jill Clayton-Smith, Consultant Clinical Geneticist, St Mary’s Hospital, Manchester, UK.

What are the symptoms?

In addition to a marbled appearance to the skin, individuals may have pink/red birth marks (see entry Vascular Birthmarks), particularly over the upper lip. Macrocephaly (large head size) is usually present along with webbing between the second and third toes and sometimes between the fingers. Occasionally, extra fingers or toes may be present. It is also common to have one side of the body which is slightly larger than the other (hemihypertrophy).

Whilst cutis marmorata can occur on its own, only individuals with the other, additional features can be said to have MCAP syndrome.

Babies with MCAP syndrome often have a high birth weight. It is common for children with this condition to have low muscle tone and so there may be initial difficulties with feeding. Children with MCAP syndrome are often slow to learn to sit and walk because they have low muscle tone and very mobile joints. Many children with MCAP syndrome learn at a slower rate than normal, but the condition is extremely variable and some affected individuals have normal development.

There are other rarer complications of MCAP syndrome which include heart problems, seizures, internal blood vessel malformations and developmental abnormalities of the brain. Many children, however, have good general health.

What are the causes?

Individuals with MCAP syndrome have a change in the genetic code of a gene called PIK3CA in some, but not all of the cells in the body. When disorders arise in this way they are referred to as ‘mosaic’ disorders.

How is it diagnosed?

Diagnosis will be based on the typical features of the syndrome being observed in a child. A magnetic resonance imaging (MRI) scan may reveal characteristic appearances including a difference in the appearance of the two halves of the brain and polymicrogyria (where the folds of the brain are unusual in appearance). Genetic testing, where available, may also confirm the diagnosis but is difficult as the gene change may not be present in blood cells and it may be necessary to test other types of cell.

How is it treated?

Treatment of MCAP syndrome involves managing the various symptoms. All children with the condition should have regular check-ups by a paediatrician. Recent studies have suggested that every child should have a heart scan, an ECG, a check for thrombophilia (abnormal blood clotting) and an MRI scan of the brain and spinal cord at diagnosis. Occasionally surgery will be recommended to drain fluid or relieve pressure within the brain. In many children, although the head is larger than average, head growth stabilises and no treatment is needed. The marbled appearance of the skin tends to get less obvious with time. Children may need physiotherapy to improve muscle tone and aid mobility.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
MCAP occurs sporadically (with no previous family history), and usually affects only one member of a family. Affected families should be referred to a genetics centre for information and advice.

Prenatal diagnosis
Ultrasound scan abnormalities including increased amniotic fluid, large head size and signs of increased fluid around the baby have been observed in some affected pregnancies. To date, specific genetic testing has not been undertaken in pregnancy.

Is there support?

M-CM UK

Website: m-cm.org.uk

The Group was established in 2015. Their aims are to support families with an M-CM/MCAP diagnosis, provide a strong patient voice in policy and research and to raise awareness of M-CM/MCAP.

Group details added December 2016.