Oculopharyngeal muscular dystrophy explained

Oculopharyngeal muscular dystrophy
Synonyms:Muscular dystrophy, oculopharyngeal
Symptoms:Dysphagia
Causes:Mutations on the PABPN1 gene
Diagnosis:Muscle biopsy
Treatment:Orthopedic devices for management [1]

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.[2]

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 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 mutation contains a GCG trinucleotide repeat [3] at the 5' end of the coding region, and expansion of this repeat which then leads to autosomal dominant oculopharyngeal muscular dystrophy (OPMD) disease.[4] [5]

Signs and symptoms

File:Lateral orbit nerves.jpg|thumb|left|400px|Extraocular muscles are shown in this image of the left eye (lateral view). Click on the structures for more information.default Picture: left eye from the side; Click to view informationpoly 1191 533 1187 447 1254 444 1279 490 1263 529 1191 533 Lateral rectuspoly 421 124 459 129 484 145 524 134 500 97 421 124 Trochlea of superior obliquepoly 470 198 456 180 450 153 452 137 459 130 483 145 483 155 501 170 530 183 519 184 470 198 Superior obliquepoly 524 134 557 136 657 156 770 191 856 222 927 248 981 273 1045 309 1101 341 1216 409 1208 374 1006 261 891 207 780 161 670 130 567 111 507 108 524 134 Superior obliquepoly 669 252 690 249 672 243 680 238 664 224 684 225 736 255 810 275 792 240 758 228 689 217 599 216 548 224 501 239 466 259 519 311 554 281 577 269 627 259 676 258 669 252 Superior rectuspoly 828 281 812 245 912 281 905 286 920 293 904 294 910 299 934 302 943 312 945 320 868 294 828 281 Superior rectuspoly 961 327 1054 369 1154 409 1228 438 1221 428 1091 366 992 315 952 298 961 327 Superior rectuspoly 1196 424 1238 441 1208 440 1172 434 1049 393 1015 368 968 346 859 311 813 294 740 265 705 256 676 258 669 252 689 249 672 243 679 238 665 224 685 226 737 255 810 275 792 240 770 219 732 213 727 197 770 211 798 232 804 219 812 246 828 281 834 293 860 304 908 318 954 333 945 320 943 312 933 302 910 299 904 294 920 292 905 287 912 281 929 287 920 276 898 271 902 261 896 250 909 254 939 276 937 263 953 270 951 297 953 298 962 327 965 335 1016 359 1054 382 1146 417 1196 424 1196 424 Oculomotor nervepoly 1608 418 1615 416 1619 421 1618 426 1580 443 1523 462 1466 474 1382 497 1382 487 1434 472 1394 467 1409 457 1452 461 1483 461 1567 437 1608 418 Oculomotor nervepoly 1564 449 1523 462 1466 474 1382 497 1379 512 1485 496 1539 484 1566 455 1564 449 Optic nervepoly 1383 475 1382 487 1434 472 1395 466 1383 475 Optic nervepoly 1559 439 1554 429 1521 425 1483 436 1462 438 1416 451 1409 457 1452 461 1483 461 1559 439 Optic nervepoly 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 Zinnpoly 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 obliquepoly 570 744 604 717 540 696 522 679 535 725 532 747 570 744 Inferior rectuspoly 659 759 814 735 962 682 1136 623 1236 589 1217 559 1178 580 1011 635 983 659 966 653 922 687 887 688 912 675 955 651 849 678 803 709 776 735 767 733 781 715 761 715 761 710 802 698 828 682 747 699 717 711 675 752 659 759 Inferior rectuspoly 1187 453 1028 454 954 461 864 451 849 444 856 502 888 516 942 525 1016 523 1051 518 1018 496 978 507 969 518 965 516 973 498 985 494 924 487 898 489 896 481 931 476 907 469 912 465 955 474 1025 487 1054 503 1046 485 1024 479 1030 466 1049 475 1062 495 1068 514 1083 509 1189 475 1187 453 Medial rectuspoly 1193 533 1124 557 1068 514 1187 475 1193 533 Optic nervepoly 1111 563 1051 518 1011 523 1004 555 985 579 995 582 1027 588 1111 563 Optic nervepoly 944 525 951 561 924 579 897 569 853 541 856 502 890 517 944 525 Optic nervepoly 964 574 988 558 988 524 955 525 962 553 964 574 Optic nervepoly 1052 581 1111 563 1123 568 1052 581 Medial rectuspoly 1126 556 1138 562 1233 530 1191 533 1126 556 Medial rectuspoly 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 ganglionpoly 912 465 908 469 931 476 896 481 898 489 924 487 985 494 973 499 965 516 969 517 978 507 1018 496 1051 518 1111 563 1123 568 1142 576 1058 606 1027 616 1005 616 1004 616 1004 616 971 626 945 632 945 634 926 644 802 675 739 694 725 702 721 708 746 699 772 689 841 674 827 683 802 698 761 710 761 715 781 715 767 733 776 735 802 710 849 678 859 672 939 649 998 631 954 651 888 687 922 687 966 653 983 659 1012 635 1033 624 1159 581 1216 559 1244 541 1240 537 1156 569 1139 562 1126 556 1124 556 1068 514 1062 495 1048 475 1030 466 1024 478 1046 485 1054 503 1025 488 912 465 Oculomotor nervepoly 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)poly 355 602 365 593 373 547 374 492 370 389 355 376 341 452 351 459 350 498 348 521 340 525 355 602 Irispoly 341 452 351 459 350 498 348 521 340 525 338 486 341 452 Pupilpoly 355 376 341 452 339 482 340 525 355 602 323 540 316 510 315 466 321 438 355 376 355 376 Anterior chamberpoly 630 396 634 439 630 569 565 574 529 593 511 494 540 414 634 439 630 396 Lateral rectuspoly 812 246 871 266 929 287 920 276 898 271 903 261 896 250 910 254 939 276 937 263 953 270 951 298 991 314 1093 367 1221 428 1216 409 1101 341 984 275 936 257 809 209 761 193 709 181 605 174 519 184 433 209 336 251 363 304 376 286 420 254 494 221 549 211 624 205 697 211 758 226 792 240 770 219 732 213 728 197 769 211 798 232 804 219 812 246 812 246 Levator palpebrae superioris musclepoly 676 258 628 260 577 269 554 281 588 307 627 355 692 363 762 343 720 288 676 258 Superior obliquepoly 599 216 586 208 551 211 494 221 488 224 501 239 548 224 599 216 599 216 Superior obliquepoly 851 546 846 572 852 573 866 576 918 596 922 594 915 587 856 552 851 546 Optic nervepoly 839 579 841 579 827 612 853 606 906 602 901 598 882 596 857 586 878 587 852 579 839 579 Medial rectuspoly 962 327 965 335 1016 359 1054 382 1146 417 1190 423 1154 409 1054 369 962 327 Orbitpoly 945 320 868 294 828 281 834 293 860 304 908 318 954 333 945 320 Orbitpoly 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 Orbitdesc bottom-rightIn terms of the signs (and symptoms) of oculopharyngeal muscular dystrophy would be consistent with the following:[2] [6]

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 fibers

In homozygous 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 PABPN1 gene. This gene suffers mutations that cause the PABPN1 protein to have extra alanine (amino acids), this manifests itself physically in the symptoms of this MD.[5]

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 autosomal dominance.[7]

The alleles, which are a variant form of a gene[8] involved in this form of MD are: PABPN1, (GCG)n EXPANSION, (GCG)8-13, PABPN1, (GCG)n EXPANSION, (GCG)7 and PABPN1, GLY12ALA.[3]

Diagnosis

The diagnosis of oculopharyngeal muscular dystrophy can be done via two methods, a muscle biopsy or a blood draw with genetic testing for GCG trinucleotide expansions in the PABPN1 gene. The genetic blood testing is more common. Additionally, a distinction between OPMD and myasthenia gravis or mitochondrial myopathy must be made, in regards to the differential diagnosis of this condition.[2]

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 along with exercises taught by a speech therapist 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, 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.[9] [10] 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.[11]

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), Jewish Ashkenazi, and Spanish Americans.[12]

See also

Further reading

Notes and References

  1. Web site: Oculopharyngeal muscular dystrophy Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. rarediseases.info.nih.gov. 3 January 2018. en.
  2. Book: Oculopharyngeal Muscular Dystrophy. Trollet. Capucine. Gidaro. Teresa. Klein. Pierre. Périé. Sophie. Butler-Browne. Gillian. Lacau St Guily. Jean. 1993-01-01. University of Washington, Seattle. Pagon. Roberta A.. Seattle (WA). 20301305. Adam. Margaret P.. Ardinger. Holly H.. Wallace. Stephanie E.. Amemiya. Anne. Bean. Lora J.H.. Bird. Thomas D.. Fong. Chin-To. Mefford. Heather C.. update 2014
  3. Web site: OMIM Entry - * 602279 - POLYADENYLATE-BINDING PROTEIN, NUCLEAR, 1; PABPN1. www.omim.org. 2016-05-29.
  4. https://www.ncbi.nlm.nih.gov/gene/8106 "PABPN1 poly(A) binding protein, nuclear 1 [Homo sapiens (human) ]"
  5. Web site: oculopharyngeal muscular dystrophy. Reference. Genetics Home. Genetics Home Reference. 2016-05-28.
  6. Web site: Oculopharyngeal muscular dystrophy. 28 May 2016.
  7. Web site: OMIM Entry - # 164300 - OCULOPHARYNGEAL MUSCULAR DYSTROPHY; OPMD. www.omim.org. 2016-05-29.
  8. Web site: What is a gene?. Reference. Genetics Home. Genetics Home Reference. 2016-05-29.
  9. Davies . Janet E. . Berger . Zdenek . Rubinsztein . David C. . Oculopharyngeal muscular dystrophy: Potential therapies for an aggregate-associated disorder . The International Journal of Biochemistry & Cell Biology . January 2006 . 38 . 9 . 1457–1462 . 10.1016/j.biocel.2006.01.016 . 16530457 .
  10. Abu-Baker . Aida . Rouleau . Guy A. . Oculopharyngeal muscular dystrophy: Recent advances in the understanding of the molecular pathogenic mechanisms and treatment strategies . Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease . February 2007 . 1772 . 2 . 173–185 . 10.1016/j.bbadis.2006.10.003 . 17110089 . 20281205 .
  11. Malerba . A. . Klein . P. . Bachtarzi . H. . Jarmin . S. A. . Cordova . G. . Ferry . A. . Strings . V. . Espinoza . M. Polay . Mamchaoui . K. . Blumen . S. C. . St Guily . J. Lacau . Mouly . V. . Graham . M. . Butler-Browne . G. . Suhy . D. A. . Trollet . C. . Dickson . G. . PABPN1 gene therapy for oculopharyngeal muscular dystrophy . Nature Communications . 31 March 2017 . 8 . 14848 . 10.1038/ncomms14848 . 28361972 . 5380963 . 2017NatCo...814848M .
  12. Web site: Oculopharyngeal muscular dystrophy Disease Your Questions Answered Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. rarediseases.info.nih.gov. 2016-05-29. 2016-08-03. https://web.archive.org/web/20160803161028/https://rarediseases.info.nih.gov/gard/7245/oculopharyngeal-muscular-dystrophy/case/34996/case-questions. dead.

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