Ullrich congenital muscular dystrophy

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Ullrich congenital muscular dystrophy
Other namesScleroatonic muscular dystrophy [1]
Autosomal recessive - en.svg
Autosomal recessive pattern is the inheritance manner of this condition
Symptoms Muscle weakness [2]
CausesMutations in the COL6A1, COL6A2, and COL6A3 gene [3]
Diagnostic method Physical exam, Medical history [3]
Medication Physical therapy, Surgery(scoliosis) [3]

Ullrich congenital muscular dystrophy is a form of congenital muscular dystrophy. It is associated with variants of type VI collagen, it is commonly associated with muscle weakness and respiratory problems, though cardiac issues are not associated with this type of CMD. [4] [5] It is named after Otto Ullrich, who is also known for the Ullrich-Turner syndrome. [6]

Contents

Signs and symptoms

The presentation of Ullrich congenital muscular dystrophy in an affected individual is as follows: [2] [7]

Genetics

In terms of the genetics of Ullrich congenital muscular dystrophy, there are mutations in the genes COL6A1, COL6A2, and COL6A3. This sub-type of muscular dystrophy is autosomal recessive in nature. [1] [8]

COL6A1 plays an important part in maintaining the human body's integrity of various tissues. Alpha 1 subunit of type VI collagen is the encoded protein. [9]

Diagnosis

Micrograph hyperkeratosis Lichen simplex chronicus - low mag.jpg
Micrograph hyperkeratosis

In terms of the diagnosis of Ullrich congenital muscular dystrophy upon inspection follicular hyperkeratosis, may be a dermatological indicator, additionally also serum creatine kinase may be mildly above normal. [5] Other exams/methods to ascertain if the individual has Ullrich congenital muscular dystrophy are:[ medical citation needed ]

Differential diagnosis

This includes [10]

Treatment

Scoliosis X-ray Wiki pre-op.jpg
Scoliosis X-ray

Treatment for Ullrich congenital muscular dystrophy can consist of physical therapy and regular stretching to prevent and reduce contractures. Respiratory support may be needed at some point by the affected individual. [3]

Though cardiac complications are not a concern in this type of CMD, in regards to respiratory issues ventilation via a tracheostomy is a possibility in some cases. [5] [11]

Prognosis

The prognosis of this sub-type of MD indicates that the affected individual may eventually have feeding difficulties. Surgery, at some point, might be an option for scoliosis. [3]

Scoliosis, which is a sideways curve of the persons vertebrate, is determined by a variety of factors, including the degree (mild or severe), in which case if possible a brace might be used by the individual. [12]

Research

Cyclosporin-A Ciclosporin-A-neutron-3D-sticks.png
Cyclosporin-A

In terms of possible research for Ullrich congenital muscular dystrophy one source indicates that cyclosporine A might be of benefit to individuals with this CMD type. [13]

According to a review by Bernardi, et al., cyclosporin A (CsA) used to treat collagen VI muscular dystrophies demonstrates a normalization of mitochondrial reaction to rotenone. [14]

See also

Related Research Articles

Muscular dystrophy Genetic disorder

Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affected, the degree of weakness, how fast they worsen, and when symptoms begin. Some types are also associated with problems in other organs.

Oculopharyngeal muscular dystrophy Medical condition

Oculopharyngeal muscular dystrophy (OPMD) is a rare form of muscular dystrophy with symptoms generally starting when an individual is 40 to 50 years old. It can be autosomal dominant neuromuscular disease or autosomal recessive. The most common inheritance of OPMD is autosomal dominant, which means only one copy of the mutated gene needs to be present in each cell. Children of an affected parent have a 50% chance of inheriting the mutant gene.

Muscle biopsy Procedure in which a piece of muscle tissue is removed from an organism and examined microscopically

In medicine, a muscle biopsy is a procedure in which a piece of muscle tissue is removed from an organism and examined microscopically. A muscle biopsy can lead to the discovery of problems with the nervous system, connective tissue, vascular system, or musculoskeletal system.

Fukuyama congenital muscular dystrophy Medical condition

Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal recessive form of muscular dystrophy mainly described in Japan but also identified in Turkish and Ashkenazi Jewish patients; fifteen cases were first described on 1960 by Dr. Yukio Fukuyama.

In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. Myopathy means muscle disease. This meaning implies that the primary defect is within the muscle, as opposed to the nerves or elsewhere. Muscle cramps, stiffness, and spasm can also be associated with myopathy.

Nemaline myopathy is a congenital, often hereditary neuromuscular disorder with many symptoms that can occur such as muscle weakness, hypoventilation, swallowing dysfunction, and impaired speech ability. The severity of these symptoms varies and can change throughout one's life to some extent. The prevalence is estimated at 1 in 50,000 live births. It is the most common non-dystrophic myopathy.

Hereditary inclusion body myopathies (HIBM) are a group of rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles.

Congenital muscular dystrophy Medical condition

Congenital muscular dystrophies are autosomal recessively-inherited muscle diseases. They are a group of heterogeneous disorders characterized by muscle weakness which is present at birth and the different changes on muscle biopsy that ranges from myopathic to overtly dystrophic due to the age at which the biopsy takes place.

Emery–Dreifuss muscular dystrophy Medical condition

Emery–Dreifuss muscular dystrophy (EDMD) is a type of muscular dystrophy, a group of heritable diseases that cause progressive impairment of muscles. EDMD affects muscles used for movement, causing atrophy, weakness and contractures. It almost always affects the heart, causing abnormal rhythms, heart failure, or sudden cardiac death. It is rare, affecting 0.39 per 100,000 people. It is named after Alan Eglin H. Emery and Fritz E. Dreifuss.

Congenital myopathy is a very broad term for any muscle disorder present at birth. This defect primarily affects skeletal muscle fibres and causes muscular weakness and/or hypotonia. Congenital myopathies account for one of the top neuromuscular disorders in the world today, comprising approximately 6 in 100,000 live births every year. As a whole, congenital myopathies can be broadly classified as follows:

Bethlem myopathy Medical condition

Bethlem myopathy is an autosomal dominant myopathy, classified as a congenital form of muscular dystrophy, that is caused by a mutation in one of the three genes coding for type VI collagen. These include COL6A1, COL6A2, and COL6A3. Gower's sign, tiptoe-walking and contractures of the joints are typical signs and symptoms of the disease. Bethlem myopathy could be diagnosed based on clinical examinations and laboratory tests may be recommended. Currently there is no cure for the disease and symptomatic treatment is used to relieve symptoms and improve quality of life. Bethlem myopathy affects about 1 in 200,000 people.

NIM811 Chemical compound

NIM811 is a mitochondrial permeability transition inhibitor. Also known as N-methyl-4-isoleucine cyclosporin, it is a four-substituted cyclosporine analogue that binds to cyclophilin, however this binary complex cannot bind to calcineurin, and therefore lacks immunosuppressive activity.

Collagen, type VI, alpha 1 Mammalian protein found in Homo sapiens

Collagen alpha-1(VI) chain is a protein that in humans is encoded by the COL6A1 gene.

Collagen, type VI, alpha 2 Mammalian protein found in Homo sapiens

Collagen alpha-2(VI) chain is a protein that in humans is encoded by the COL6A2 gene.

Collagen, type VI, alpha 3

Collagen alpha-3(VI) chain is a protein that in humans is encoded by the COL6A3 gene. This protein is an alpha chain of type VI collagen that aids in microfibril formation. As part of type VI collagen, this protein has been implicated in Bethlem myopathy, Ullrich congenital muscular dystrophy (UCMD), and other diseases related to muscle and connective tissue.

SEPN1

Selenoprotein N is a protein that in humans is encoded by the SEPN1 gene.

Collagen VI (ColVI) is a type of collagen primarily associated with the extracellular matrix of skeletal muscle. ColVI maintains regularity in muscle function and stabilizes the cell membrane. It is synthesized by a complex, multistep pathway that leads to the formation of a unique network of linked microfilaments located in the extracellular matrix (ECM). ColVI plays a vital role in numerous cell types, including chondrocytes, neurons, myocytes, fibroblasts, and cardiomyocytes. ColVI molecules are made up of three alpha chains: α1(VI), α2(VI), and α3(VI). It is encoded by 6 genes: COL6A1, COL6A2, COL6A3, COL6A4, COL6A5, and COL6A6. The chain lengths of α1(VI) and α2(VI) are about 1,000 amino acids. The chain length of α3(VI) is roughly a third larger than those of α1(VI) and α2(VI), and it consists of several spliced variants within the range of 2,500 to 3,100 amino acids.

Muscle–eye–brain disease Medical condition

Muscle–eye–brain (MEB) disease, also known as muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A3 (MDDGA3), is a kind of rare congenital muscular dystrophy (CMD), largely characterized by hypotonia at birth. Patients have muscular dystrophy, central nervous system abnormalities and ocular abnormalities. The condition is degenerative.

References

  1. 1 2 RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Congenital muscular dystrophy, Ullrich type". www.orpha.net. Retrieved 2016-05-11.
  2. 1 2 Reference, Genetics Home. "collagen VI-related myopathy". Genetics Home Reference. Retrieved 2016-05-11.
  3. 1 2 3 4 5 "Ullrich congenital muscular dystrophy | Disease | Treatment | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2016-05-11.
  4. "Ullrich congenital muscular dystrophy - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-11.
  5. 1 2 3 Foley, A. Reghan; Mohassel, Payam; Donkervoort, Sandra; Bolduc, Véronique; Bönnemann, Carsten G. (January 31, 1993). Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E.; Bean, Lora JH; Gripp, Karen W.; Mirzaa, Ghayda M.; Amemiya, Anne (eds.). GeneReviews®. University of Washington, Seattle. PMID   20301676 via PubMed.
  6. O. Ullrich: Kongenitale, atonisch-sklerotische Muskeldystrophie, ein weiterer Typus der heredodegenerativen Erkrankungen des neuromuskulären Systems. In: Zeitschrift für die gesamte Neurologie und Psychiatrie. 126, 1930, p. 171, doi:10.1007/BF02864097.
  7. Bönnemann, Carsten G. (2011). "Chapter 5 - The collagen VI-related myopathies: Ullrich congenital muscular dystrophy and Bethlem myopathy". Handbook of Clinical Neurology. Elsevier. pp. 81–96. Retrieved 16 September 2020.
  8. Bönnemann, Carsten G. (2011-01-01). "The collagen VI-related myopathies Ullrich congenital muscular dystrophy and Bethlem myopathy". Handbook of Clinical Neurology. 101: 81–96. doi:10.1016/B978-0-08-045031-5.00005-0. ISSN   0072-9752. PMC   5207779 . PMID   21496625.  via ScienceDirect  (Subscription may be required or content may be available in libraries.)
  9. "COL6A1 collagen type VI alpha 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-05-11.
  10. Bushby KM, Collins J, Hicks D (2014) Collagen type VI myopathies. Adv Exp Med Biol 802:185-199
  11. "Congenital Muscular Dystrophy Treatment & Management: Medical Care, Surgical Care, Consultations". 2019-09-04.{{cite journal}}: Cite journal requires |journal= (help)
  12. "Scoliosis: MedlinePlus". www.nlm.nih.gov. Retrieved 2016-05-12.
  13. "OMIM Entry - # 254090 - ULLRICH CONGENITAL MUSCULAR DYSTROPHY 1; UCMD1". omim.org. Retrieved 2016-05-12.
  14. Bernardi, Paolo; Bonaldo, Paolo (2013-05-01). "Mitochondrial Dysfunction and Defective Autophagy in the Pathogenesis of Collagen VI Muscular Dystrophies". Cold Spring Harbor Perspectives in Biology. 5 (5): a011387. doi:10.1101/cshperspect.a011387. ISSN   1943-0264. PMC   3632061 . PMID   23580791.

Further reading