Oculopharyngeal muscular dystrophy - Rare Dermatology News

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Disease Profile

Oculopharyngeal muscular dystrophy

1-9 / 100 000

US Estimated

Europe Estimated

Age of onset

Adult

ICD-10

G71.0

Inheritance

Most cases of OPMD are inherited in an autosomal dominant manner, which means one copy of the altered (mutated) gene in each cell is sufficient to cause the condition.^[2]^[4] Individuals have two copies of each gene; one copy having been inherited from each parent. An individual with the autosomal dominant form of OPMD may have inherited the condition from an affected parent, or less commonly, the condition may occur for the first time in the affected individual. Each child of an affected individual with this form of OPMD has a 50% (1 in 2) chance to be affected and a 50% chance to be unaffected.

Less commonly, OPMD is inherited in an autosomal recessive manner, which means that both copies of the disease-causing gene in each cell must have a mutation for an individual to be affected. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene (and are referred to as carriers), but they typically do not show signs and symptoms of the condition.^[2] When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) chance to be affected, a 50% (1 in 2) chance to be a carrier like each of the parents, and a 25% chance to be unaffected and not be a carrier. The children of an individual with autosomal recessive OPMD will always be carriers (obligate heterozygotes) for the disease-causing mutation. The risk of a child being affected if his/her parent has autosomal recessive OPMD is less than 1%.^[4]

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

OPMD; Muscular dystrophy, oculopharyngeal

Summary

Oculopharyngeal muscular dystrophy (OPMD) is a genetic disorder characterized by slowly progressing muscle disease (myopathy) affecting the muscles of the upper eyelids and the throat. Onset is typically during adulthood, most often between 40 and 60 years of age. Symptoms may include: eyelid drooping (ptosis), arm and leg weakness, and difficulty swallowing (dysphagia).^[1] There are two types of OPMD, distinguished by their patterns of inheritance. They are known as the autosomal dominant and autosomal recessive types.^[2] Both types are caused by mutations in the PABPN1 gene.^[1]^[2]Treatment depends on the signs and symptoms present in each individual. Ptosis and dysphagia can be managed with surgery; however, recurrence of symptoms commonly occurs 5-15 years after intervention.^[1]^[3]

Symptoms

OPMD is characterized by muscle weakness that begins in adulthood, typically after age 40. The first symptom in people with this disorder is usually droopy eyelids (ptosis), followed by difficulty swallowing (dysphagia). The swallowing difficulties begin with food, but as the condition progresses, liquids can be difficult to swallow as well. Many people with this condition have weakness and wasting (atrophy) of the tongue. These problems with food intake may cause malnutrition. Some affected individuals also have weakness in other facial muscles.^[1]^[2]^[3]^[4]

Individuals with OPMD may also have double vision (diplopia) and frequently have weakness in the muscles near the center of the body (proximal muscles), particularly muscles in the upper legs and hips. The weakness progresses slowly over time, and people may need the aid of a cane or a walker. Rarely, affected individuals need wheelchair assistance.^[1]^[2]^[3]^[4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormality of the pharynx		0000600
Elevated serum creatine kinase	Elevated blood creatine phosphokinase Elevated circulating creatine phosphokinase Elevated creatine kinase Elevated serum CPK Elevated serum creatine phosphokinase High serum creatine kinase Increased CPK Increased creatine kinase Increased creatine phosphokinase Increased serum CK Increased serum creatine kinase Increased serum creatine phosphokinase [ more ]	0003236
Myopathy	Muscle tissue disease	0003198
Ophthalmoplegia	Eye muscle paralysis	0000602
Ptosis	Drooping upper eyelid	0000508
Ragged-red muscle fibers		0003200
Rimmed vacuoles		0003805
Spondylolisthesis	Displacement of one backbone compared to another Slipped backbone [ more ]	0003302
5%-29% of people have these symptoms
Mask-like facies	Expressionless face Lack of facial expression Mask-like facial appearance [ more ]	0000298
Percent of people who have these symptoms is not available through HPO
Adult onset	Symptoms begin in adulthood	0003581
Autosomal dominant inheritance		0000006
Distal muscle weakness	Weakness of outermost muscles	0002460
Dysarthria	Difficulty articulating speech	0001260
Dysphagia	Poor swallowing Swallowing difficulties Swallowing difficulty [ more ]	0002015
Facial palsy	Bell's palsy	0010628
Gait disturbance	Abnormal gait Abnormal walk Impaired gait [ more ]	0001288
Limb muscle weakness	Limb weakness	0003690
Neck muscle weakness	Floppy neck	0000467
Progressive	Worsens with time	0003676
Progressive ptosis	Progressive drooping of upper eyelid	0007838
Proximal muscle weakness	Weakness in muscles of upper arms and upper legs	0003701

Cause

OPMD is caused by mutations in the PABPN1 gene. The PABPN1 gene provides instructions for making the PABPN1 protein that is active (expressed) throughout the body. In cells, the PABPN1 protein plays an important role in processing molecules called messenger RNAs (mRNAs), which serve as genetic blueprints for making proteins. The protein acts to protect the mRNA from being broken down and allows it to move within the cell.^[2]^[4]

The PABPN1 gene contains a section of DNA called a GCN repeat, which normally repeats around 10 times. In cases of OPMD, this section of DNA is repeated 11-17 times. This results in the protein having too many of an amino acid called alanine. The extra alanine causes the PABPN1 protein to form clumps within muscle cells that cannot be broken down. These clumps are thought to impair the normal function of muscle cells and eventually cause cells to die. The progressive loss of muscle cells most likely causes the muscle weakness seen in people with OPMD. It is not known why abnormal PABPN1 proteins seem to affect muscle cells in only certain parts of the body.^[2]^[4]

Diagnosis

Genetic testing is available for oculopharyngeal muscular dystrophy (OPMD). GeneTests lists the names of laboratories that are performing genetic testing for this condition. To view the contact information for the clinical laboratories conducting testing click here. Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, individuals that are interested in learning more will need to work with a health care provider or a genetics professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment

Treatment of oculopharyngeal muscular dystrophy (OPMD) mainly focuses on the specific signs and symptoms present in each individual. Severe drooping of the eyelid (ptosis) may be treated with plastic surgery on the eyelid (blepharoplasty). The goal of this surgery is to raise the eyelid so that the affected individual can see. Individuals with severe difficulty swallowing (dysphagia) may have a surgical procedure known as cricopharyngeal myotomy. In this procedure, the cricopharyngeal muscle of the throat is cut so that when swallowing occurs, the muscle remains relaxed allowing the passage of food or liquid. Orthopedic devices such as canes, leg braces, or walkers can assist individuals who have difficulty walking. Other treatment is symptomatic and supportive.^[1]^[4]

Related diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include oculopharyngodistal myopathy, myasthenia gravis, Steinert myotonic dystrophy, proximal myotonic myopathy, congenital fibrosis of extraocular muscles, blepharophimosis-epicanthus inversus-ptosis syndrome (see these terms), autosomal dominant distal myopathy, and mitochondrial myopathy. Visit the Orphanet disease page for more information.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

European Alliance of Neuromuscular Disorders Associations
MDG Malta 4
Gzira Road
Gzira, Intl GAR 04
Malta
Telephone: 003-56 -21 346688
E-mail: [email protected]
Website: https://www.eamda.eu/

Organizations Providing General Support

Muscular Dystrophy Association (MDA)
222 S Riverside Plaza
Suite 1500
Chicago, IL 60606
Toll-free: 1-833-275-6321 (Helpline)
E-mail: [email protected]
Website: https://www.mda.org
Muscular Dystrophy UK
61A Great Suffolk Street
London, SE1 0BU United Kingdom
Toll-free: 0800 652 6352 (Helpline)
Telephone: (+44) 0 020 7803 4800
E-mail: [email protected]
Website: https://www.musculardystrophyuk.org/

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The Muscular Dystrophy Association (MDA) provides additional information about oculopharyngeal muscular dystrophy in their publication entitled, Oculopharyngeal Muscular Dystrophy (OPMD)
MedlinePlus Genetics contains information on Oculopharyngeal muscular dystrophy. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
Orphanet
Orphanet
PubMed is a searchable database of medical literature and lists journal articles that discuss Oculopharyngeal muscular dystrophy. Click on the link to view a sample search on this topic.

References

Lee M. Oculopharyngeal Muscular Dystrophy. National Organization for Rare Disorders (NORD). 2012; https://rarediseases.org/rare-diseases/oculopharyngeal-muscular-dystrophy/.
Oculopharyngeal muscular dystrophy. Genetics Home Reference (GHR). December 2008; https://ghr.nlm.nih.gov/condition/oculopharyngeal-muscular-dystrophy.
Nissing J. Oculopharyngeal muscular dystrophy. Orphanet. May 2016; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=270.
Trollet C, Gidaro T, Klein P, et al. Oculopharyngeal muscular dystrophy. GeneReviews. Februaru 20, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1126/.

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Adult

G71.0

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Testing Resources

Treatment

Related diseases

Organizations

Organizations Supporting this Disease

Organizations Providing General Support

Learn more

Where to Start

In-Depth Information

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.