/
/

Centronuclear myopathy

This is part of Rare diseases.

Diagnosis: Centronuclear myopathy

Synonyms: Myotubular myopathy


Publication date: 2013-12-30
Version: 1.0

The disease

Centronuclear myopathy is a hereditary muscle disease associated with the incomplete development of muscle cells, which causes muscle weakness. There are three forms of the disease with different degrees of severity and patterns of inheritance.

The most severe form of the disease is myotubular myopathy, inherited via the X chromosome. The term myotubular refers to the way the muscle cells in this disease are similar to immature muscle cells (myotubes) found in the foetus. In 1966, these muscle abnormalities were described by American neurologist AJ Spiro and his associates. In the following year, a research team led by JH Sher suggested the name centronuclear myopathy for all three forms of the disease. The term centronuclear refers to the combination of immature muscle cells and centrally-located cell nuclei.

In 1985, JZ Heckmatt and his colleagues confirmed that there were three distinct forms of centronuclear myopathy. Apart from the serious form associated with the X chromosome, there is also a less severe autosomal recessive form, and a milder autosomal dominant variant. In practice, boundaries are not always distinct and the disease can range from a form characterized by relatively mild symptoms to an extremely serious condition.

Occurrence

All three forms of centronuclear myopathy are rare. There is no exact information on how common the disease is, but it occurs in fewer than 10 individuals per 100,000. The form associated with the X chromosome is found in approximately one boy in every 50,000. Every year in Sweden a few children are born with one form of the three variants of the disease. The total number of people with centronuclear myopathy in the country is unknown.

Cause

The form of the disease associated with the X chromosome, myotubular myopathy, is caused by a genetic mutation on the X chromosome (Xq28). The affected gene is named MTM1, and it controls the formation of (codes for) the myotubularin protein. The mutation causes low levels of myotubularin in the muscle fibres. This protein is important in the signalling systems of muscle fibres as it regulates phosphate levels in intracellular signalling substances. One result of low levels of myotubularin is that muscle fibres remain immature. The process by which this happens is not yet fully understood, but is believed to be linked to abnormalities in the formation of cell membranes. The result is that affected muscle fibres resemble underdeveloped foetal muscle cells.

The mutation in gene DNM2 on chromosome 19 (19p13.2) is the cause of the autosomal dominant form of the disease. This gene codes for the dynamin 2 protein, which is involved in the formation of the cell membranes of muscles. This protein also affects an important system of channels, the T tubules, found in muscle fibres. The mutation usually results in a mild form of the disease, manifesting for the first time in late childhood or adulthood. Other mutations in gene DNM2 can cause another of the inherited forms of polyneuropathy, Charcot-Marie-Tooth disease, type 2B. In rare cases, the mutation can also lead to a condition associated with elements of centronuclear myopathy, polyneuropathy, and mild cognitive impairment.

Another cause of the dominant form of the disease, giving rise to symptoms from the neonatal period onwards, is a mutation in gene RYR1 (19q15.2). In rare cases, mutations in genes MTMR14 (3p25.3) or MYF6 (12q21.31) have been identified as causing the dominant form of centronuclear myopathy.

The autosomal recessive form may be caused by genetic mutations in gene BIN1 on chromosome 2 (2q14.3), which codes for the amphiphysin 2 protein. This protein allows dynamin 2 to regulate the formation of T tubules and the transportation of membrane proteins within the muscle cells.

Heredity

Centronuclear myopathy has three possible patterns of inheritance: X-linked recessive, autosomal dominant and autosomal recessive.

An X-linked recessive inheritance pattern is caused by a mutated gene located on the X chromosome, which is one of the chromosomes determining sex. Men have one X chromosome and one Y chromosome, while women have two X chromosomes. Inherited X-linked recessive disorders usually occur only in men, being passed down via a healthy female carrier who has one normal and one mutated gene. Sons of female carriers of a mutated gene run a 50 per cent risk of inheriting the disease and daughters run the same risk of being healthy carriers of a mutated gene. A man with an inherited X-linked recessive disease cannot pass it on to his sons, but all his daughters will be carriers of the mutated gene.

Figure: X-linked recessive inheritance  via a healthy female carrier

An autosomal dominant pattern of inheritance means that one of the parents has the disease, and so has one normal gene and one mutated gene. Sons and daughters of this parent have a 50 per cent risk of inheriting the disease. Children who do not inherit the mutated gene do not have the disease and do not pass it on.

Figure: Autosomal dominant inheritance

An autosomal recessive inheritance pattern means that both parents are healthy carriers of a mutated gene. In each pregnancy with the same parents there is a 25 per cent risk that the child will inherit double copies of the mutated gene (one from each parent). In this case the child will have the disease. In 50 per cent of cases the child inherits only one mutated gene (from one parent only) and, like both parents, will be a healthy carrier of the mutated gene. In 25 per cent of cases the child will not have the disease and will not be a carrier of the mutated gene.

Figure: Autosomal recessive inheritance

A person with an inherited autosomal recessive disease has two mutated genes. If this person has a child with a person who is not a carrier of the mutated gene, all the children will inherit the mutated gene but they will not have the disorder. If a person with an inherited autosomal recessive disease has children with a healthy carrier of the mutated gene (who has one mutated gene) there is a 50 per cent risk of the child having the disorder, and a 50 per cent risk of the child being a healthy carrier of the mutated gene.

Centronuclear myopathy can also be caused by a new mutation. This means that the genetic mutation occurs in an individual for the first time and is not inherited from either parent. Consequently, parents with a child with a new mutation generally do not have an increased risk of having another child with the disorder. However, the new genetic mutation will be hereditary and an adult with this mutation risks passing on the mutated gene to his/her children.

Symptoms

Childhood

The X-linked recessive inheritance pattern affects only boys and causes severe symptoms directly after birth. Autosomal dominant and autosomal recessive forms of the disease are usually milder, affect both girls and boys, and are associated with a later appearance of symptoms.

X-linked recessive form

Children with centronuclear myopathy, particularly boys with the X-linked recessive form, show very early symptoms of very poor muscle tone (hypotonus) and muscle weakness. Muscle weakness may sometimes manifest during the second half of the pregnancy in the form of increased amounts of amniotic fluid and very weak foetal movements. Normally a healthy foetus swallows amniotic fluid, but if muscle weakness is very pronounced the foetus cannot swallow, resulting in increased volumes of fluid. There is also an increased risk of early miscarriage. Children are often premature and have a low birth weight in relation to their length.

The primary symptom of severe muscular weakness in newborns with the disease is breathing difficulties. This often presents directly after birth and the child may require mechanical breathing assistance in the form of a respirator. Other early symptoms indicating poor muscle tone and muscular weakness are a lack of spontaneous movement, inability to balance the head and a weak cry. The child often feels “floppy” and slack when lifted or carried. He or she also often has problems sucking and feeding. Limited muscle activity in the foetal stage can result in the newborn having stiff joints, particularly the knees or hips.

Other symptoms include undescended testicles (testes retention), weak eye musculature and a larger head than normal, with or without hydrocephalus. A few children may have liver abnormalities or liver haemorrhages, which can be serious. Rare symptoms associated with children with the X-linked recessive form of the disease are abnormal bleeding, brain haemorrhages, gallstones, kidney stones and calcifications, pyloric stenosis (a narrowing of the opening from the stomach to the first part of the small intestine) and early puberty.

In the most severe form, myotubular myopathy, muscle weakness and respiratory problems are often so serious that the child dies during the first year of life, most commonly during the first months. The cause is usually respiratory failure, sometimes in combination with cardiac insufficiency or pneumonia, both of which can occur as a result of poor respiratory function.

Children with other forms of centronuclear myopathy may also run an increased risk of death due to respiratory failure in the neonatal period. The risk is poorly understood, but it is thought to be much lower than in cases of myotubular myopathy.

A few boys with the X-linked form of the disease survive infancy. Where the disease has proved less severe, the boys have become stronger as they have got older and their respiratory function has improved. Some learn to walk, although later than normal. Muscle weakness in boys with a more severe form of the disease is so severe that they require a respirator and help with most daily activities.

Autosomal recessive form

The autosomal recessive form of centronuclear myopathy usually presents for the first time in childhood. Initially, muscle weakness is most apparent in the face and eye muscles as well as the upper arms and thighs. Weakness in the eye muscles causes squinting and drooping of the upper eyelids (ptosis).

Autosomal dominant form

In the autosomal dominant form, symptoms often appear somewhat later than in the autosomal recessive form. They are also a little milder. Otherwise, symptoms are similar in both forms of centronuclear myopathy. In childhood, as in the neonatal period, there is a risk of respiratory failure. In serious situations, for example if the patient develops pneumonia, respiratory failure can be life-threatening.

Many children with the disease have stiff joints and curvature of the spine (scoliosis).

Teenage years and adulthood

In a few boys with the X-linked form of the disease, their muscle function has improved and they have survived into adulthood.

In the two other forms of centronuclear myopathy, muscle weakness may be so mild that it is not discovered before the individual reaches adulthood. Symptoms are the same as in childhood but also often include difficulties in walking, and drooping eyelids (ptosis). Muscle condition may slowly deteriorate and be accompanied by wasting of the muscles (atrophy). Adults may experience respiratory failure, which in turn may cause cardiac insufficiency.

Diagnosis

A diagnosis of centronuclear myopathy is made primarily on the basis of muscle weakness in combination with the absence of tendon reflexes. A muscle biopsy (where a piece of muscle tissue is examined microscopically) will also reveal typical signs of the disease.

When there is muscle weakness, different tests can be carried out to identify muscular disease or other types of conditions affecting the muscles. Creatine kinase, CK, is a protein found in muscles, which in certain muscle diseases leaks into the blood. In centronuclear myopathy, a blood test for CK often shows that levels are normal.

An electromyogram (EMG), a type of neurophysiological examination, provides information on the functioning of muscle fibres and whether they respond normally to nerve impulses. In centronuclear myopathy this examination will often reveal signs of muscle disease, while peripheral nerve function remains normal.

If centronuclear myopathy or another form of congenital muscle disease (myopathy) is suspected, a muscle biopsy can be of great help in arriving at a diagnosis. A muscle biopsy will show that muscle fibres are generally immature for the age of the child, and instead resemble those of a foetus of approximately 20 weeks gestational age. The fibres are small in diameter and the nuclei are in a central position. In the central parts of the fibres, those proteins (contractile proteins) which enable the muscle to contract are often absent. Instead, there is an accumulation of mitochondria, small units in the cell which convert energy into forms that it can use. There are also many other proteins which are normally found only in immature muscles during the foetal stage.

As the appearance of muscle fibres is similar in all forms of the disease, a muscle biopsy cannot establish which form of centronuclear myopathy is present. The age at which the symptoms present, their severity and the gender of the patient, all provide help in establishing the form of the disease.

To reach a more exact diagnosis it is important to identify whether there is a pattern of inheritance for centronuclear myopathy or muscle weakness. The X-linked form of the disease is strongly indicated if a muscle biopsy from the mother shows immature muscle fibres with central nuclei.

The diagnosis can be confirmed by DNA analysis. It is important that the family is offered genetic counselling at the time the diagnosis is made. Carrier and prenatal diagnosis, as well as pre-implantation genetic diagnosis (PGD) in association with IVF (in vitro fertilization), are available in families where the mutation is known.

Treatment/interventions

Children with more severe forms of centronuclear myopathy often require medical help immediately after birth, primarily in the form of a respirator. Help with feeding via a blood vessel or PEG (percutaneous endoscopic gastrostomy) may also be necessary. The first period of life is critical from a medical perspective and is also a very difficult time for parents. The wait for a diagnosis is often compared to living in a vacuum, and wide variations in the severity of the disease mean that even after the diagnosis, it is difficult to know how the disease will progress and affect the child’ s development and prognosis.

In the X-linked form of centronuclear myopathy, information on the type of genetic mutation can help in giving a prognosis although there may be significant variations between children with the same type of mutation. For this reason it is important that there is a continuous dialogue between parents and healthcare services on such subjects as diagnosis, symptoms, expectations for the future, possible forms of treatment and supportive measures, and that goals for healthcare services are regularly reviewed. These goals should reflect the needs of the individual and take into account the severity of the child’s illness as well as the family’ s situation and attitudes.

There is insufficient knowledge about the extent to which it is appropriate to use respiratory support. For this reason, judgements should be made on an individual basis. Regardless of the chosen level of medical intervention, the physical and mental wellbeing of the child is crucial.

In the milder forms of the disease and in children with the X-linked form who survive the first months, muscle strength may gradually improve. Treatment is then directed at supporting physical functions which are negatively affected by muscle weakness. Treatment of symptoms from the motor system requires the collaboration of a physician, a physiotherapist and an occupational therapist working in a habilitation team, as well as an orthopaedic surgeon and an orthopaedic engineer.

Orthoses (orthopaedic appliances or supports) and, for example, a wheeled walker, can make walking easier. Sometimes a manual or, in more severe cases, an electric wheelchair may be necessary along with an electric lift and a standing support device. Congenital and acquired joint stiffness is often treated with orthopaedic surgery. A physiotherapist can give advice and instructions on different exercises to prevent stiffness recurring. A spinal brace can stabilise the trunk and counteract scoliosis (curvature of the spine).

Interventions that reduce the risk of respiratory tract infections may include an augmented vaccination programme. If respiratory function is impaired, breathing exercises are needed to counteract the accumulation of secretions in the airways, and if symptoms indicate reduced lung function, tests should be carried out for confirmation. When lung function is impaired mechanical ventilation, using a home ventilator with a breathing mask, is of great help at nights. If pulmonary function deteriorates further, respirator use on a more permanent basis may be considered.

A cough assistance device is a respiratory aid that has come to be widely used in Sweden in recent years. After a few assisted inhalations it draws up phlegm from the respiratory tract if the individual’s own ability to cough is impaired.

In rare cases there may be signs of cardiac insufficiency, for example in the form of breathlessness, tiredness and swollen lower legs, which can be treated with diuretics and heart stimulants.

A habilitation team offers support and treatment within the medical, educational, psychological, social and technical fields. Help includes assessment, treatment, the provision of aids, information on the specific disability, and counselling. It also includes information on all available support offered in the community, as well as advice on adjustments to the home environment and other places where the child spends time. The family may also need help in coordinating different measures.

Habilitation is planned on the basis of each child’s needs, and may vary over time. There should be close collaboration between people close to the child or young person.

Psychological support adapted to age and maturity should be available continuously while the child is growing up. Even small children need their questions answered. Parents and siblings should also be offered support from a counsellor or psychologist.

Swedish public agencies can offer different forms of support to facilitate the family’s everyday life. Personal assistance can help the child/teenager lead an active life despite what might be extensive disabilities.

Older teenagers and adults require regular medical follow-ups and habilitation tailored to their individual needs.

Depending on the individual’s degree of functional disability, new work routines and individualized adaptations and aids may be necessary to provide help in daily life. Occupational therapists and assistive technology consultants help with the purchase and trial of appropriate aids. If required, the school, home, car and workplace can be adapted to individual needs.

Practical advice

--

National and regional resources in Sweden

In Sweden’s habilitation centres there is expertise in the medical and psychological care of children with muscle conditions. University hospitals in Gothenburg (The Queen Silvia Children’s Hospital), Linköping, Lund/ Malmö, Stockholm (Astrid Lindgren Children’s Hospital), Umeå, Uppsala and Örebro also have special muscle teams for examining and caring for children with muscle diseases.

In Stockholm (Karolinska University Hospital), Gothenburg (Sahlgrenska University Hospital/Mölndal), Linköping and Örebro there are neuromuscular units specializing in muscle diseases in adults.

The Department of Clinical Genetics at Uppsala University Children’s Hospital carries out genetic testing for X-linked centronuclear myopathy.

Resource personnel

Children and young people

Chief Physician Eva Kimber, Uppsala University Children’s Hospital, SE-751 85 Uppsala, Sweden. Tel: +46 18 611 00 00.

Senior Physician Ulla Lindskog, Ekhaga Regional Habilitation Centre, University Hospital, SE-581 85 Linköping, Sweden. Tel: +46 10 103 20 00.

Senior Physician Lars Palm, Paediatric Centre, Skåne University Hospital, SE-205 02 Malmö, Sweden. Tel: +46 40 33 10 00.

Senior Physician Lars Palmér, The Children’s Clinic, Norrland University Hospital, SE-901 85 Umeå, Sweden. Tel: +46 90 785 00 00.

Professor Tomas Sejersen, Paediatric Neurology, Astrid Lindgren Children’s Hospital, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 777 00.

Professor Már Tulinius, The Queen Silvia Children’s Hospital, Sahlgrenska University Hospital/Östra, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 40 00.

Adults

Senior Physician Snjolaug Arnardottir, Neurology Clinic, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 700 00.

Senior Physician Tomas Börsbo, University Clinic of Rehabilitation Medicine, Danderyd Hospital AB, SE-182 88 Stockholm, Sweden. Tel: +46 8 655 00 00.

Associate Professor Christopher Lindberg, Neuromuscular Centre, Sahlgrenska University Hospital/ Mölndal, SE-413 45 Gothenburg, Sweden. Tel: +46 31 342 10 00.

Senior Physician Björn Lindvall, Muscle Centre, Örebro University Hospital, SE-701 85 Örebro, Sweden. Tel: +46 19 602 10 00, email: bjorn.lindvall@orebroll.se.

Associate Professor Göran Solders, Neurology Clinic, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden. Tel: +46 8 585 800 00.

Courses, exchanges of experience, recreation

RBU (find under heading, “Organizations for the disabled/patient associations etc.”) organizes camps for children and young people with muscle conditions every summer, and training for parents on an annual basis. Some summers they also arrange family weeks for children with muscular disorders and their families.

Organizations for the disabled/patient associations etc.

RBU, The Swedish National Association for Disabled Children and Young People, St Eriksgatan 44, Box 8026, SE-104 20 Stockholm, Sweden. Tel: +46 8 677 73 00, fax: +46 8 677 73 09, email: info@rbu.se, www.rbu.se.

RBU’s regional associations have one or more representatives of families with children affected by muscular disorders. Contact is mediated via RBU. The RBU website has information on this disorder, www.rbu.se, as well as a leaflet available free from the association. (In Swedish only.)

NHR, The Swedish Association for Persons with Neurological Disabilities, St Eriksgatan 44, Box 49084, SE-100 28 Stockholm, Sweden. Tel: +46 8 677 70 10, fax: +46 8 677 13 15, email: nhr@nhr.se, www.nhr.se. NHR has a reference group for neuromuscular diseases.

In the US, the family organization Myotubular Myopathy Resource Group produces information material and passes on contact information between families with the disease. Email: myopathy@optonline.net, www.mtmrg.org.

Courses, exchanges of experience for personnel

--

Research and development

Further international research is under way into those proteins (myotubularin, dynamin 2 and amphiphysin 2) which are defective in cases of centronuclear myopathy, in order to gain insight into the mechanisms of the disease. Work is under way into establishing a common database in Europe and the rest of the world for centronuclear myopathy, other forms of congenital myopathies, the Congenital Muscle Disease International Registry (CMDIR) and congenital muscular dystrophies, www.treat-nmd.eu/cmd/patient-registries/CMDIR.

In Sweden a database of neuromuscular diseases is being assembled, which in the near future will include centronuclear myopathy and other congenital myopathies, www.nmis.se. This database is important in order for professionals to be able to estimate how common a disease is, how symptoms are caused by different mutations, the effects of different treatments, and also to act as a basis for possible future studies.

Information material

Short summaries of all the database texts are available as leaflets, in Swedish only. They can be printed out or ordered by selecting the Swedish version, and then clicking on the leaflet icon which will appear under, “Mer hos oss” in the column on the right-hand side.

Barn och ungdomar med muskelsjukdomar, 2010. (In Swedish only.) Information from RBU. (See under “Organizations for the disabled/patient associations.”)

Jag har en sjukdom men jag är inte sjuk (2004). (In Swedish only.) A book about young people whose lives are affected by muscle diseases. Book published by Save the Children, ISBN 91-7321-121-4, also available on CD. Order from Save the Children: www.rb.se.

Doktorn kunde inte riktigt laga mig (2007). A book (in Swedish) by Christina Renlund on small children, disease and disability. Published by Gothia, ISBN 978-91-7205-553-7.

Information in English can be found on the website of the Myotubular Myopathy Resource Group, www.mtmrg.org.

EAMDA (European Alliance of Muscular Dystrophy Associations) collates information and resources from patient groups in Europe, which it publishes in its newsletter along with information on relevant publications and videos. The website address is www.eamda.net.

Literature

Biancalana V, Caron O, Gallati S, Baas F, Kress W, Novelli G et al. Characterisation of mutations in 77 patients with X-linked myotubular myopathy, including a family with a very mild phenotype. Hum Genet 2003; 112: 135-142.

Bitoun M, Maugenre S, Jeannet PY, Lacene E, Ferrer X, Laforet P et al. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat Genet 2005; 37: 1207-1209.

Heckmatt J, Sewry CA, Hodes D, Dubowitz V. Congenital centronuclear (myotubular) myopathy: a clinical, pathological and genetic study in eight children. Brain 1985; 108: 941-964.

Helliwell TR, Ellis IH, Appleton RE. Myotubular myopathy: morphological, immunohistochemical and clinical variation. Neuromuscul Disord 1998; 8: 152-161.

Herman GE, Finegold M, Zhao W, de Gouyon B, Metzenberg A. Medical complications in long-term survivors with X-linked myotubular myopathy. J Pediatr 1999; 134: 206-214.

Hoffjan S, Thiels C, Vorgerd M, Neuen-Jacob E, Epplen JT Kress W. Extreme phenotypic variability in a German family with X-linked myotubular myopathy associated with E404K mutation in MTM1. Neuromuscul Disord 2006; 16: 749-753.

Jungbluth H, Wallgren-Pettersson C, Laporte J. Centronuclear (myotubular) myopathy. Orphanet J Rare Diseases 2008; 3: 26.

Maggi L, Scoto M, Cirak S, Robb SA, Klein A, Lillis S et al. Congenital myopathies - Clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom. Neuromuscul Disord 2013; Feb 7. doi:pii: S0960-8966. [Epub ahead of print]

McEntegart M, Parsons G, Buj-Bello A, Biancalana V, Fenton I, Little M et al. Genotype-phenotype correlations in X-linked myotubular myopathy. Neuromuscul Disord 2002; 12: 939-946.

Nicot AS, Toussaint A, Tosch V, Kretz C, Wallgren-Pettersson C, Iwarsson E et al. Mutations in amphiphysin 2 (BIN 1) disrupt interaction with dynamin 2, and cause autosomal recessive centronuclear myopathy. Nat Genet 2007; 39: 1134-1139.

Pierson CR, Tomczak K, Agrawal P, Moghadaszadeh B Beggs A. X-linked myotubular and centronuclear myopathies. J Neuropathol Exp Neurol 2005; 64: 555-564.

Sher JH, Rimalovski AB, Athanassiades TJ, Aronson SM. Familial centronuclear myopathy: a clinical and pathological study. Neurology 1967; 17: 727-742.

Spiro AJ, Shy GM, Gonatas NK. Myotubular myopathy. Persistence of fetal muscle in adolescent boy. Arch Neurol 1966; 14: 1-14.

Wang CH, Dowling JJ, North K, Schroth MK, Sejersen T, Shapiro F et al. Consensus statement on standard of care for congenital myopathies. J Child Neuro 2012; 27: 363-382.

Database references

OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim 
Search: myotubular myopathy, X-linked
myopathy, centronuclear, autosomal recessive
myopathy, centronuclear, autosomal dominant

GeneReviews (University of Washington)
www.genetests.org (select “GeneReviews”, then “Titles”)
Search: myotubular myopathy, X-linked

Orphanet, European database
www.orpha.net 
Search: centronuclear (myotubular) myopathy

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Professor Thomas Sejersen, Astrid Lindgren Children’s Hospital, Sweden.

The relevant organizations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Date of publication: 2013-12-30
Version: 1.0
Publication date of the Swedish version: 2013-06-03

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 422, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.