'''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.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gtr/conditions/C0410179/|title=Ullrich congenital muscular dystrophy - Conditions - GTR - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-05-11}}</ref><ref name="nih">[https://www.ncbi.nlm.nih.gov/books/NBK1503/ GeneReviews/NCBI/NIH/UW entry on Collagen Type VI-Related Disorders]</ref> It is named after Otto Ullrich, who is also known for the [[Turner syndrome|Ullrich-Turner syndrome]].<ref>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]].</ref>
{{Short description|A form of congenital muscular dystrophy}}
'''Ullrich congenital muscular dystrophy''' (UCMD) is a rare genetic disorder characterized by muscle weakness and joint abnormalities. It is one of the forms of [[congenital muscular dystrophy]], a group of muscle diseases that are present at birth or in early infancy.
==Signs and symptoms==
==Etiology==
The presentation of Ullrich congenital muscular dystrophy in an affected individual is as follows:<ref name="web">{{Cite web|url=https://ghr.nlm.nih.gov/condition/collagen-vi-related-myopathy#genes|title=collagen VI-related myopathy|last=Reference|first=Genetics Home|website=Genetics Home Reference|access-date=2016-05-11}}</ref><ref>{{cite book |last1=Bönnemann |first1=Carsten G. |title=Handbook of Clinical Neurology |date=2011 |publisher=Elsevier |pages=81–96 |url=https://www.sciencedirect.com/science/article/pii/B9780080450315000050 |accessdate=16 September 2020 |language=en |chapter=Chapter 5 - The collagen VI-related myopathies: Ullrich congenital muscular dystrophy and Bethlem myopathy}}</ref>
UCMD is caused by mutations in the genes that encode for [[collagen]] VI, a protein that is essential for the structural integrity of muscle tissue. The specific genes involved are [[COL6A1]], [[COL6A2]], and [[COL6A3]]. These mutations lead to defects in the collagen VI protein, resulting in muscle weakness and other symptoms associated with the disorder.
* [[Muscle]] weakness
==Clinical Features==
* Difficulty walking
Individuals with UCMD typically present with muscle weakness that is evident at birth or in early childhood. The muscle weakness is often accompanied by joint contractures, which are limitations in the range of motion of the joints. Other common features include:
* [[Contractures]] (predominantly in proximal muscles, e.g. neck)
* [[Hypotonia]] (decreased muscle tone)
* Joint looseness (predominantly in distal joints)
* [[Hyperlaxity]] (increased flexibility) of distal joints
* [[Kyphoscoliosis]] (curvature of the spine)
==Genetics==
* Respiratory difficulties due to weakness of the respiratory muscles
* Skin changes such as [[keratosis pilaris]]
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.<ref name="orpha">{{Cite web|url=http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=75840|title=Orphanet: Congenital muscular dystrophy, Ullrich type|last=RESERVED|first=INSERM US14 -- ALL RIGHTS|website=www.orpha.net|access-date=2016-05-11}}</ref><ref>{{Cite journal|last=Bönnemann|first=Carsten G.|date=2011-01-01|title=The collagen VI-related myopathies Ullrich congenital muscular dystrophy and Bethlem myopathy|journal=Handbook of Clinical Neurology|volume=101|pages=81–96|doi=10.1016/B978-0-08-045031-5.00005-0|issn=0072-9752|pmid=21496625|pmc=5207779}}{{Subscription or libraries|sentence|via=[[ScienceDirect]]}}</ref>
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.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1291|title=COL6A1 collagen type VI alpha 1 [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2016-05-11}}</ref>
The diagnosis of UCMD is based on clinical examination, family history, and genetic testing. Muscle biopsy may show characteristic changes, and immunohistochemical staining can reveal abnormalities in collagen VI. Genetic testing can confirm mutations in the COL6A1, COL6A2, or COL6A3 genes.
==Management==
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.<ref name=nih/> Other exams/methods to ascertain if the individual has Ullrich congenital muscular dystrophy are:{{medical citation needed|date=May 2016}}
There is currently no cure for UCMD, and treatment is primarily supportive. Management strategies include:
* [[MRI]]
* Physical therapy to maintain mobility and prevent contractures
* [[Biopsy]] muscle
* Orthopedic interventions for joint deformities
* Genetic testing
* Respiratory support, such as non-invasive ventilation, for individuals with respiratory muscle weakness
* Regular monitoring by a multidisciplinary team including neurologists, pulmonologists, and orthopedic specialists
===Differential diagnosis===
==Prognosis==
The prognosis for individuals with UCMD varies depending on the severity of the condition. Some individuals may have a relatively stable course, while others may experience progressive muscle weakness and respiratory complications. Early intervention and supportive care can improve quality of life and functional outcomes.
This includes<ref name=Bushby2014>Bushby KM, Collins J, Hicks D (2014) Collagen type VI myopathies. Adv Exp Med Biol 802:185-199</ref>
Treatment for Ullrich congenital muscular dystrophy can consist of physical therapy and regular stretching to prevent and reduce [[contracture]]s. Respiratory support may be needed at some point by the affected individual.<ref name="gar">{{Cite web|url=https://rarediseases.info.nih.gov/gard/4769/ullrich-congenital-muscular-dystrophy/resources/8|title=Ullrich congenital muscular dystrophy {{!}} Disease {{!}} Treatment {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|website=rarediseases.info.nih.gov|access-date=2016-05-11}}</ref>
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.<ref name=nih/><ref>{{Cite journal|title=Congenital Muscular Dystrophy Treatment & Management: Medical Care, Surgical Care, Consultations|url=http://emedicine.medscape.com/article/1180214-treatment|date=2019-09-04}}</ref>
===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]].<ref name=gar/>
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.<ref>{{Cite web|url=https://www.nlm.nih.gov/medlineplus/scoliosis.html|title=Scoliosis: MedlinePlus|website=www.nlm.nih.gov|access-date=2016-05-12}}</ref>
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.<ref>{{Cite web|url=https://omim.org/entry/254090|title=OMIM Entry - # 254090 - ULLRICH CONGENITAL MUSCULAR DYSTROPHY 1; UCMD1|website=omim.org|access-date=2016-05-12}}</ref>
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]].<ref>{{Cite journal|last=Bernardi|first=Paolo|last2=Bonaldo|first2=Paolo|date=2013-05-01|title=Mitochondrial Dysfunction and Defective Autophagy in the Pathogenesis of Collagen VI Muscular Dystrophies|journal=Cold Spring Harbor Perspectives in Biology|volume=5|issue=5|doi=10.1101/cshperspect.a011387|issn=1943-0264|pmc=3632061|pmid=23580791|pages=a011387}}</ref>
==See also==
==See also==
* [[Muscular dystrophy]]
* [[Congenital muscular dystrophy]]
* [[Congenital muscular dystrophy]]
* [[Collagen]]
==References==
* [[Genetic disorder]]
{{Reflist}}
* [[Muscle biopsy]]
[[Category:Congenital disorders]]
==Further reading==
[[Category:Muscular dystrophy]]
* {{Cite book|url=https://books.google.com/books?id=SjfKybobUIYC|title=Encyclopedia of Human Genetics and Disease [2 volumes]|last=Ph.D|first=Evelyn B. Kelly|date=2013-01-07|publisher=ABC-CLIO|isbn=9780313387142|language=en}}
* {{Cite web|url=http://www.guideline.gov/content.aspx?id=49881&search=Ullrich+congenital+muscular+dystrophy|title=National Guideline Clearinghouse {{!}} Evidence-based guideline summary: evaluation, diagnosis, and management of congenital muscular dystrophy: report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular and Electrodiagnostic Medicine.|website=www.guideline.gov|access-date=2016-05-12|archive-url=https://web.archive.org/web/20160408034807/http://www.guideline.gov/content.aspx?id=49881|archive-date=2016-04-08|url-status=dead}}
* {{cite journal|last1=Hicks|first1=D.|last2=Lampe|first2=A. K.|last3=Laval|first3=S. H.|last4=Allamand|first4=V.|last5=Jimenez-Mallebrera|first5=C.|last6=Walter|first6=M. C.|last7=Muntoni|first7=F.|last8=Quijano-Roy|first8=S.|last9=Richard|first9=P.|last10=Straub|first10=V.|last11=Lochmuller|first11=H.|last12=Bushby|first12=K. M. D.|title=Cyclosporine A treatment for Ullrich congenital muscular dystrophy: a cellular study of mitochondrial dysfunction and its rescue|journal=Brain|date=16 November 2008|volume=132|issue=1|pages=147–155|doi=10.1093/brain/awn289|url=http://brain.oxfordjournals.org/content/brain/132/1/147.full.pdf|accessdate=12 May 2016|pmid=19015158}}
== External links ==
{{Medical resources
| DiseasesDB = 33679
| ICD10 = G71.2
| ICD9 =
| ICDO =
| OMIM = 254090
| MedlinePlus =
| eMedicineSubj =
| eMedicineTopic =
| MeshID = C537521
| GeneReviewsNBK = NBK1503
| GeneReviewsName = Collagen Type VI-Related Disorders
| Orphanet = 75840
}}
{{Scholia|topic}}
{{Diseases of myoneural junction and muscle}}
{{Scleroprotein disease}}
[[Category:Myoneural junction and neuromuscular diseases]]
Ullrich congenital muscular dystrophy (UCMD) is a rare genetic disorder characterized by muscle weakness and joint abnormalities. It is one of the forms of congenital muscular dystrophy, a group of muscle diseases that are present at birth or in early infancy.
UCMD is caused by mutations in the genes that encode for collagen VI, a protein that is essential for the structural integrity of muscle tissue. The specific genes involved are COL6A1, COL6A2, and COL6A3. These mutations lead to defects in the collagen VI protein, resulting in muscle weakness and other symptoms associated with the disorder.
Individuals with UCMD typically present with muscle weakness that is evident at birth or in early childhood. The muscle weakness is often accompanied by joint contractures, which are limitations in the range of motion of the joints. Other common features include:
The diagnosis of UCMD is based on clinical examination, family history, and genetic testing. Muscle biopsy may show characteristic changes, and immunohistochemical staining can reveal abnormalities in collagen VI. Genetic testing can confirm mutations in the COL6A1, COL6A2, or COL6A3 genes.
The prognosis for individuals with UCMD varies depending on the severity of the condition. Some individuals may have a relatively stable course, while others may experience progressive muscle weakness and respiratory complications. Early intervention and supportive care can improve quality of life and functional outcomes.
