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 An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosom ...

dominant

neuromuscular disease A neuromuscular disease is any disease affecting the peripheral nervous system (PNS), the neuromuscular junction, or skeletal muscle, all of which are components of the motor unit. Damage to any of these structures can cause muscle atrophy and wea ...

recessive In genetics, dominance is the phenomenon of one variant ( allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant an ...

. 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.update 2014 Autosomal dominant inheritance is the most common form of inheritance. Less commonly, OPMD can be inherited in an autosomal recessive pattern, which means that two copies of the mutated

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

need to be present in each cell, both parents need to be carriers of the mutated gene, and usually show no signs or symptoms. The

PABPN1 Polyadenylate-binding protein 2 (PABP-2) also known as polyadenylate-binding nuclear protein 1 (PABPN1) is a protein that in humans is encoded by the ''PABPN1'' gene. PABN1 is a member of a larger family of poly(A)-binding proteins in the human ge ...

mutation contains a GCG tri

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecu ...

repeat at the 5' end of the coding region, and expansion of this repeat which then leads to autosomal dominant oculopharyngeal muscular dystrophy (OPMD) disease.https://www.ncbi.nlm.nih.gov/gene/8106 "PABPN1 poly(A) binding protein, nuclear 1 Homo sapiens (human) ]11 OCT 2014.

Signs and symptoms

File:Lateral orbit nerves.jpg, left, 400px, Extraocular muscles are shown in this image of the left eye (lateral view). Click on the structures for more information. default Human eye, Picture: left eye from the side; Click to view information poly 1191 533 1187 447 1254 444 1279 490 1263 529 1191 533

Lateral rectus Lateral is a geometric term of location which may refer to: Healthcare * Lateral (anatomy), an anatomical direction * Lateral cricoarytenoid muscle * Lateral release (surgery), a surgical procedure on the side of a kneecap Phonetics * Lateral ...

poly 421 124 459 129 484 145 524 134 500 97 421 124

Trochlea of superior oblique The trochlea of superior oblique is a pulley-like structure in the eye. The tendon of the superior oblique muscle passes through it. Situated on the superior nasal aspect of the frontal bone, it is the only cartilage found in the normal orbit. Th ...

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Superior rectus The superior rectus muscle is a muscle in the orbit. It is one of the extraocular muscles. It is innervated by the superior division of the oculomotor nerve (III). In the primary position (looking straight ahead), its primary function is elevation ...

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poly 961 327 1054 369 1154 409 1228 438 1221 428 1091 366 992 315 952 298 961 327

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Oculomotor nerve The oculomotor nerve, also known as the third cranial nerve, cranial nerve III, or simply CN III, is a cranial nerve that enters the orbit through the superior orbital fissure and innervates extraocular muscles that enable most movements of ...

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poly 1564 449 1523 462 1466 474 1382 497 1379 512 1485 496 1539 484 1566 455 1564 449

Optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual information from the retina to the brain. In humans, the optic nerve is derived fro ...

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poly 1262 529 1216 559 1236 589 1332 562 1453 552 1402 538 1379 512 1382 497 1382 497 1382 487 1383 475 1394 467 1409 457 1416 452 1463 438 1422 433 1387 419 1370 385 1367 356 1350 362 1280 351 1269 364 1238 377 1208 374 1216 409 1221 428 1228 437 1238 441 1254 444 1279 490 1262 529

Annulus of Zinn The common tendinous ring, also known as the annulus of Zinn, or annular tendon, is a ring of fibrous tissue surrounding the optic nerve at its entrance at the apex of the orbit. It is the common origin of the four recti muscles of the group of e ...

poly 460 728 518 748 570 745 604 717 659 643 695 564 756 557 803 589 723 706 675 752 609 781 543 785 494 765 460 728

Inferior oblique The inferior oblique muscle or obliquus oculi inferior is a thin, narrow muscle placed near the anterior margin of the floor of the orbit. The inferior oblique is one of the extraocular muscles, and is attached to the maxillary bone (origin) and ...

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Inferior rectus Inferior may refer to: * Inferiority complex * An anatomical term of location * Inferior angle of the scapula, in the human skeleton * ''Inferior'' (book), by Angela Saini * ''The Inferior'', a 2007 novel by Peadar Ó Guilín See also *Junior (di ...

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poly 1111 563 1051 518 1011 523 1004 555 985 579 995 582 1027 588 1111 563

poly 944 525 951 561 924 579 897 569 853 541 856 502 890 517 944 525

poly 964 574 988 558 988 524 955 525 962 553 964 574

poly 1052 581 1111 563 1123 568 1052 581 Medial rectus poly 1126 556 1138 562 1233 530 1191 533 1126 556 Medial rectus poly 945 632 971 626 1004 616 1004 616 993 607 997 593 1034 596 1049 593 1043 584 1027 588 995 582 986 579 1004 556 1011 523 988 524 988 558 964 574 961 553 954 525 944 525 950 561 924 579 896 568 853 541 839 520 835 524 856 552 915 587 922 594 918 596 866 576 852 573 824 572 825 578 852 579 878 587 857 586 882 596 901 598 906 602 853 606 826 612 805 621 808 626 841 615 868 612 920 610 939 612 945 632

Ciliary ganglion The ciliary ganglion is a bundle of nerve parasympathetic ganglion located just behind the eye in the posterior orbit. It is 1–2 mm in diameter and in humans contains approximately 2,500 neurons. The ganglion contains postganglionic parasympath ...

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poly 460 728 518 748 531 747 535 727 522 679 541 696 604 717 659 643 696 564 756 558 803 590 727 700 741 694 774 683 819 623 808 626 805 621 827 612 841 579 825 578 824 572 846 572 851 546 835 524 839 521 853 541 856 502 849 444 841 406 815 350 778 303 729 263 701 257 676 258 719 288 761 343 691 363 626 355 634 439 630 569 565 574 529 593 511 494 540 414 634 439 626 354 587 307 554 281 519 311 466 259 420 290 386 330 355 376 370 389 374 487 373 547 365 593 355 602 395 668 460 728

Globe (human eye) The globe of the eye, or bulbus oculi, is the eyeball apart from its appendages. A hollow structure, the bulbus oculi is composed of a wall enclosing a cavity filled with fluid with three coats: the sclera, choroid, and the retina. Normally, the b ...

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Iris Iris most often refers to: *Iris (anatomy), part of the eye *Iris (mythology), a Greek goddess * ''Iris'' (plant), a genus of flowering plants * Iris (color), an ambiguous color term Iris or IRIS may also refer to: Arts and media Fictional ent ...

poly 341 452 351 459 350 498 348 521 340 525 338 486 341 452

Pupil The pupil is a black hole located in the center of the Iris (anatomy), iris of the Human eye, eye that allows light to strike the retina.Cassin, B. and Solomon, S. (1990) ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing ...

poly 355 376 341 452 339 482 340 525 355 602 323 540 316 510 315 466 321 438 355 376 355 376

Anterior chamber The anterior chamber ( AC) is the aqueous humor-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. Hyphema, anterior uveitis and glaucoma are three main pathologies in this area. In hyphema, blood f ...

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Levator palpebrae superioris muscle The levator palpebrae superioris ( la, elevating muscle of upper eyelid) is the muscle in the orbit that elevates the upper eyelid. Structure The levator palpebrae superioris originates from inferior surface of the lesser wing of the sphenoid bon ...

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poly 839 579 841 579 827 612 853 606 906 602 901 598 882 596 857 586 878 587 852 579 839 579 Medial rectus poly 962 327 965 335 1016 359 1054 382 1146 417 1190 423 1154 409 1054 369 962 327

Orbit In celestial mechanics, an orbit is the curved trajectory of an object such as the trajectory of a planet around a star, or of a natural satellite around a planet, or of an artificial satellite around an object or position in space such as ...

poly 945 320 868 294 828 281 834 293 860 304 908 318 954 333 945 320

poly 1238 441 1208 440 1172 434 1049 393 1015 368 968 346 859 311 813 294 740 265 729 263 778 303 815 350 841 406 849 444 864 451 954 461 1028 454 1187 453 1189 475 1187 447 1254 444 1238 441

desc bottom-right In terms of the signs (and symptoms) of oculopharyngeal muscular dystrophy would be consistent with the following: :::::::::::::::::::* Ptosis :::::::::::::::::::*Weakness of the

extraocular muscles The extraocular muscles (extrinsic ocular muscles), are the seven extrinsic muscles of the human eye. Six of the extraocular muscles, the four recti muscles, and the superior and inferior oblique muscles, control movement of the eye and the oth ...

:::::::::::::::::::*

Dysphagia Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or liq ...

:::::::::::::::::::*Aspiration pneumonia (complication) :::::::::::::::::::*

Proximal Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position ...

limb weakness Though the aforementioned signs/symptoms are the most common, there have been cases though rare, where the peripheral nervous system has had involvement with significant reduction of

myelinated Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be l ...

fibers In

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

cases, this muscular dystrophy is severe and starts earlier in the affected individuals life.

Genetics

The genetics of this type of muscular dystrophy revolve around the

gene. This gene suffers mutations that cause the PABPN1 protein to have extra

alanine Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side ...

(

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

), this manifests itself physically in the symptoms of this MD. The expansion caused by the mutations on the PABPN1 gene ultimately interrupts the cellular mechanics of poly(A) RNA. In most cases oculopharyngeal muscular dystrophy is inherited via

dominance. The

alleles An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chrom ...

, which are a variant form of a gene involved in this form of MD are: PABPN1, (GCG)n EXPANSION, (GCG)8-13, PABPN1, (GCG)n EXPANSION, (GCG)7 and PABPN1, GLY12ALA.

Diagnosis

The diagnosis of oculopharyngeal muscular dystrophy can be done via two methods, a

muscle biopsy 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, vascula ...

or a blood draw with

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

for GCG trinucleotide expansions in the PABPN1 gene. The genetic blood testing is more common. Additionally, a distinction between OPMD and

myasthenia gravis Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, ...

mitochondrial myopathy Mitochondrial myopathies are types of myopathies associated with mitochondrial disease. On biopsy, the muscle tissue of patients with these diseases usually demonstrate "ragged red" muscle fibers. These ragged-red fibers contain mild accumulati ...

must be made, in regards to the differential diagnosis of this condition.

Treatment

Currently no cure or specific treatment exists to eliminate the symptoms or stop the disease progression. A consistent diet planned with the help of a

dietitian A dietitian, medical dietitian, or dietician is an expert in identifying and treating disease-related malnutrition and in conducting medical nutrition therapy, for example designing an enteral tube feeding regimen or mitigating the effects of ...

along with exercises taught by a

speech therapist Speech is a human vocal communication using language. Each language uses phonetic combinations of vowel and consonant sounds that form the sound of its words (that is, all English words sound different from all French words, even if they are th ...

can assist with mild symptoms of dysphagia. Surgical intervention can also help temporarily manage symptoms related to the ptosis and dysphagia. Cutting one of the throat muscles internally, an operation called

cricopharyngeal myotomy Cricopharyngeal myotomy is a surgical sectioning of the cricopharyngeus muscle, also known as the upper esophageal sphincter, that has been advocated for the treatment of cricopharyngeal spasm Cricopharyngeal spasms occur in the cricopharyngeus ...

, can be one way to ease symptoms in more severe cases. However, for a majority of people, the benefits from such treatments are only temporary. There is currently no treatment available to address the proximal limb weakness. Many of those affected with the proximal limb weakness will eventually require assistive devices such as canes, braces or a wheelchair. As with all surgical procedures, they come with many risk factors. As the dysphagia becomes more severe, patients become malnourished, lose significant weight, become dehydrated and suffer from repeated incidents of aspiration pneumonia. These last two are often the cause of death.

Epidemiology

The disease is found across 5 continents (30 countries) and is frequently seen in French Canadians, with a prevalence 1:1000. OPMD affects males and females equally, and affected individuals have been found in Europe (

France France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...

Jewish Jews ( he, יְהוּדִים, , ) or Jewish people are an ethnoreligious group and nation originating from the Israelites Israelite origins and kingdom: "The first act in the long drama of Jewish history is the age of the Israelites""The ...

Ashkenazi, and

Spanish Spanish might refer to: * Items from or related to Spain: **Spaniards are a nation and ethnic group indigenous to Spain **Spanish language, spoken in Spain and many Latin American countries **Spanish cuisine Other places * Spanish, Ontario, Can ...

Americans.

References

External links

{{Disorders of transcription and post transcriptional modification Muscular dystrophy Rare diseases Autosomal dominant disorders