Advanced searches left 3/3
Search only database of 8 mil and more summaries

Oculopharyngeal muscular dystrophy

Summarized by PlexPage
Last Updated: 02 July 2021

* If you want to update the article please login/register

General | Latest Info

Oculopharyngeal muscular dystrophy

Other namesMuscular dystrophy, oculopharyngeal
SpecialtyNeurology
SymptomsDysphagia
CausesMutations on the PABPN1 gene
Diagnostic methodMuscle biopsy
TreatmentOrthopedic devices for management

Oculopharyngeal muscular dystrophy is a genetic condition characterized by muscle weakness that begins in adulthood, typically after age 40. The term Oculopharyngeal refers to the eyes and part of the throat called the pharynx. Affected individuals usually first experience weakness of muscles in both eyelids that causes droopy eyelids. Ptosis can worsen over time, causing eyelid to impair vision, and in some cases, limit eye movement. Along with ptosis, affected individuals develop weakness of throat muscles that cause difficulty swallowing. Dysphagia begins with dry food, but over time, liquids can also become difficult to swallow. Dysphagia can cause saliva to accumulate and wet-sounding voice. Many people with Oculopharyngeal muscular dystrophy also have weakness and wasting of tongue. These problems with food intake may cause malnutrition, choking, or bacterial lung infection called aspiration pneumonia. Individuals with Oculopharyngeal muscular dystrophy frequently have weakness in muscles near the center of the body, particularly muscles in the shoulders, upper legs, and hips. Weakness slowly gets worse, and people may need the aid of a cane or walker. Rarely, affected individuals need wheelchair assistance. Rarely, individuals have a severe form of Oculopharyngeal muscular dystrophy with muscle weakness that begins before age 45, and have trouble walking independently by age 60. These individuals often also have disturbances in nerve function, gradual loss of intellectual functioning, and psychiatric symptoms such as depression or strongly held false beliefs. Mutations in the PABPN1 gene cause Oculopharyngeal muscular dystrophy. The PABPN1 gene provides instructions for making protein that is found throughout the body. The PABPN1 protein plays an important role in processing molecules called messenger RNAs, which serve as genetic blueprints for making proteins. PABPN1 alters a region at the end of mRNA molecules that protects mRNA from being break down. The PABPN1 protein is also involved in transporting mRNA within cell. The PABPN1 protein contains an area where 10 copies of protein building block alanine occur in a row. This stretch of alanines is know as the polyalanine tract. The role of polyalanine tract in normal PABPN1 protein function is unknown. Mutations in the PABPN1 gene that cause Oculopharyngeal muscular dystrophy result in PABPN1 protein with an abnormally long polyalanine tract that includes between 11 and 18 alanines. Typically, affect Individuals with shorter polyalanine tracts tend to have milder signs and symptoms that develop later in life compared to those with longer polyalanine tracts. Extra alanines cause PABPN1 protein to form nonfunctional clumps within muscle cells. These clumps accumulate and are thought to impair normal functioning of muscle cells, eventually causing cell death. The resulting loss of muscle cells over time most likely causes muscle weakness seen in people with Oculopharyngeal muscular dystrophy. In severe cases, it is likely that intranuclear inclusions affect nerve cells as well as muscle cells.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Signs and symptoms

Symptoms of oculopharyngeal muscular Dystrophy usually do not begin until mid-40s or 50s but can occur earlier. A person with OPMD may first notice drooping eyelids, which gradually lead to tipping head backward to see properly. Besides droopy eyelids, patients might first notice that they tend to choke frequently and may have difficulty swallowing. In the autosomal dominant form of OPMD, initial symptoms typically occur between 43 to 60 years of age. In the recessive form of OPMD, initial symptoms typically occur after age 60. 1 Other symptoms associated with OPMD include tongue weakness, proximal lower extremity weakness, wet voice due to pooling saliva, limitation of upward gaze, facial muscle weakness, and proximal upper extremity weakness.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Diagnosis

Oculopharyngeal muscular Dystrophy is a rare form of muscular Dystrophy that causes progressive muscle weakness predominantly in eye and throat muscles. Patients usually appear healthy before the onset of disease symptoms, typically between the ages of 40 to 60. OPMD is a genetic condition that is most commonly inherited in autosomal dominant manner, although more rareA autosomal recessive inheritance is know. People with autosomal recessive form of OPMD often have a milder form of disease that starts much later in life. Genetic mutations responsible for both inherited forms of OPMD are on the PABPN1 gene. They cause production of abnormal protein clumps in certain groups of muscles their impair their function.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Treatment

Research in Cambridge co-fund by Muscular Dystrophy Campaign and Wellcome Trust has found that a chemical called cystamine reduces symptoms of oculopharyngeal Muscular Dystrophy in cells grow in laboratory and mouse model of the condition. Human muscle cells grow in the laboratory and treated with cystamine had fewer protein clumps that are characteristic of condition and less muscle cell death. In mice, cystamine delays onset of muscle weakness and improves muscle strength. Drugs based on the action of cystamine may now be target for development to treat OPMD. OPMD is a rare inherited condition that typically appears between the ages of 40 and 50 years. One of the first signs is drooping of eyelids and there can also be swallowing difficulties. Many years later, muscle weakness progresses to hip and shoulder muscles. OPMD is caused by changes in gene that carry information for protein called PABPN1. In unaffected individuals, gene has a piece of code repeated ten times, but in most OPMD patients this piece of code is repeated between 12 and 17 times. These extra repeats cause protein to form clumps inside muscle cells, where it is toxic. Other diseases such as Huntington disease have similar types of change of genetic code in different genes which cause protein clumping in the brain. Researchers working on Huntingtons disease have found that a chemical called cystamine is able to reduce formation of these protein clumps, so Prof. Rubinszteins laboratory in Cambridge decided to test if it could also be of value for OPMD.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Systemic management

Clinical characteristics: Oculopharyngeal muscular dystrophy is characterized by ptosis and dysphagia due to selective involvement of muscles of the eyelids and pharynx, respectively. For the vast majority of individuals with typical OPMD, mean age of onset of ptosis is usually 48 years and of dysphagia 50 years; in 5 %-10 % of individuals with severe OPMD, onset of ptosis and dysphagia occur before age 45 years and are associated with lower limb girdle weakness starting around age 60 years. Swallowing difficulties, which determine prognosis, increases the risk for potentially life-threatening aspirations pneumonia and poor nutrition. Other manifestations as disease progress can include limitation of upward gaze, tongue atrophy and weakness, chewing difficulties, wet voice, facial muscle weakness, axial muscle weakness, and proximal limb girdle weakness predominantly in lower limbs. Some individuals with severe involvement will eventually need a wheelchair. Neuropsychological tests have show altered scores in executive functions in some. Genetic counseling: OPMD is inherited in autosomal dominant manner. Risk to sibs of proband depends on the genetic status of parents of proband: if one parent of proband is heterozygous for GCN repeat expansion in PABPN1 and the other parent has two normal alleles, risk to sibs of inheriting GCN repeat expansion is 50 %. If both parents of proband are heterozygous for GCN repeat expansion, sibs have a 25 % risk of inheriting two GCN repeat expansions and 50 % risk of inheriting one GCN repeat expansion. If one parent of proband has biallelic GCN repeat expansions and the other parent has two normal alleles, all sibs will inherit GCN repeat expansion. If one parent of proband has biallelic GCN repeat expansions and the other parent is heterozygous for GCN repeat expansion, sibs of proband have a 50 % risk of inheriting biallelic GCN repeat expansions and 50 % risk of inheriting one GCN repeat expansion. Sibs who inherit either one or two GCN repeat expansions will be affect.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Causes

While no cure for OPMD currently exist, symptoms can be managed with surgery to correct ptosis as well as speech and occupational therapy to overcome muscle weakness in the throat and limbs. Life expectancy with such symptom management is generally close to normal for people with OPMD. Muscular Dystrophy News is strictly news and information website about disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek advice of your physician or other qualified health provider with any questions you may have regarding medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Standard Therapies

Oculopharyngeal muscular dystrophy is late onset rare autosomal dominant muscular dystrophy. It affects 1: 100000 people in Europe but it is more common in population groups such as Bukharan Jews and in Quebec, likely due to founder effects. OPMD is characterized by progressive eyelid drooping, swallowing difficulties and proximal limb weakness. It is caused by mutation in poly binding protein nuclear 1 gene that introduces abnormal expansion of alanine-encoding N trinucleotide repeat in the coding region of exon 1 with 11-18 repeats leading to a mutant protein with an expanded number of alanines in the N terminal domain. PABPN1 is involved in several steps of mRNA and non-coding RNA biogenesis: PABPN1 controls mRNA poly tail length and regulates use of alternative polyadenylation sites with direct effect on mRNA levels and stability. It is involved in splicing regulation and in long non-coding RNA and small nucleolar RNA processing. It also has an important role in poly-mediate RNA decay or export from nucleus as well as in RNA hyperadenylation. Finally, PABPN1 has been shown to be required for paraspeckle formation as well as for RNA editing. PABPN1 expression level varies across mouse and human tissues, and is exceptionally low in skeletal muscle. Mutate expPABPN1 is prone to forming intranuclear aggregates but only in skeletal muscle. To date, exact consequences of the presence of these aggregates in muscle still remain poorly understood, but recent studies have suggested that expPABPN1 aggregates that also sequester wild-type PABPN1 in heterozygous patients could itself contribute to phenotypes associated with OPMD by loss of function mechanism. This pathological function of PABPN1 aggregates is supported by the fact that higher frequency of aggregates is observed in severe homozygous patients. In addition, reducing PABPN1 aggregation by supplementing drugs such as trehalose or other suppose chaperones has consistently demonstrated enhanced cell survival in cell models of OPMD and improved muscle weakness in both mouse and Drosophila models. Apoptosis and deregulation of ubiquitin-proteasome system have also been proposed as potential downstream pathological events triggered by aggregates. There is currently no cure for OPMD and one of the only options for patients is surgical cricopharyngeal myotomy to improve swallowing and surgical treatment of ptosis. Some innovative therapies are under development, including phase I / IIa cell therapy trial involving autologous myoblast transplantation that has shown improvement in swallowing capacity of OPMD patients with cell dose effect. Several studies have shown promising results in animal models of disease, mainly in Drosophila and in the A17 mouse model, where expPABPN1 is overexpressed under control of human skeletal muscle actin promoter. A Gene therapy approach test in A17 mice showed strong recovery from the disease. As mentioned above, anti-aggregation pharmacological strategies have shown positive results both in vitro and in vivo in the same A17 mouse model of OPMD and intravenous injection of trehalose is currently being used in a phase II clinical trial.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

Sources

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions.

* Please keep in mind that all text is machine-generated, we do not bear any responsibility, and you should always get advice from professionals before taking any actions

logo

Plex.page is an Online Knowledge, where all the summaries are written by a machine. We aim to collect all the knowledge the World Wide Web has to offer.

Partners:
Nvidia inception logo

© All rights reserved
2021 made by Algoritmi Vision Inc.

If you believe that any of the summaries on our website lead to misinformation, don't hesitate to contact us. We will immediately review it and remove the summaries if necessary.

If your domain is listed as one of the sources on any summary, you can consider participating in the "Online Knowledge" program, if you want to proceed, please follow these instructions to apply.
However, if you still want us to remove all links leading to your domain from Plex.page and never use your website as a source, please follow these instructions.