155:
Ultimately, the tumorigenesis of schwannomas is not solely dependent on one gene locus alone. In regards to the SMARCB1 and NF2 genes, it is important to understand constitutional mutations and somatic mutations. Constitutional mutations are the first inactivation events that are often small mutations, such as point mutations and deletion/insertion of single base pairs. Somatic mutations are the second mutations that occur and may also be another small mutation or the loss of the remaining allele of the gene. Schwannomas from one patient share the same constitutional mutations but have distinct somatic mutations. In addition, the constitutional mutation may be present in non-tumor.
43:
67:
114:. When Schwann cells proliferate out of control in an encapsulation it is called a schwannoma. Although schwannomas are benign they become detrimental when the growing tumor compresses the nerve. Schwannomas on sensory nerve axons cause chronic severe pain. Treatment options for schwannomas are to surgically remove them, have radiation, cyberknife or intracapsular enucleation. Previous designations for schwannomas include neurinoma and neurilemmoma.
1667:
1697:
1707:
1687:
1677:
348:). An acoustic neuroma is a schwannoma on the vestibular nerve in the brain. This nerve is involved in hearing and patients with vestibular schwannomas experience hearing loss. However, bilateral vestibular schwannomas (vestibular schwannomas on both sides of the brain) do not occur in schwannomatosis. Juvenile vestibular tumors do not occur either.
149:
A mechanism involving both the SMARCB1 and NF2 genes may be responsible for the development of the disease because tumor analysis of schwannomas indicates the presence of inactivating mutations in both the SMARCB1 and NF2 genes. However, there is speculation about the involvement of an unidentified
292:
Gamma knife radiosurgery can be performed on head tumors to help stop growth of a tumor, although there is no guarantee that it will work. The
University of Pittsburgh published their experience with over 829 cases and reported 97% of patients had long term tumor control (defined as requiring no
154:
in patients with familial schwannomatosis. Some schwannomatosis patients do not have SMARCB1 or NF2 mutations. Furthermore, many patients exhibit somatic mosaicism for mutations in the NF2 or SMARCB1 gene, which means that some somatic cells have the mutation and some do not in the same patient.
166:
for mutations in the SMARCB1 gene have an increased risk to develop a malignant kidney tumor in early childhood but if they survive to adulthood, they may be predisposed to the development of schwannomas. One schwannomatosis patient had a mutation in exon 2 of the SMARCB1 gene. Another patient
307:
As most schwannomas are benign, many doctors will take the "watch and wait" approach and leave the tumors alone until they start causing harmful side effects. Schwannomatosis patients have multiple tumors and the risks of having so many surgeries outweigh the
95:, central nervous system tumors, and other neurological complications, excluding hallmark signs of NF. The exact frequency of schwannomatosis cases is unknown, although some populations have noted frequencies as few as 1 case per 1.7 million people.
828:
275:
In isolated regions of the body schwannomas are small and difficult to locate. Intraoperative sonography offers invaluable assistance in such cases by localizing small schwannomas and decreasing operative time and extent of the surgical
175:. In this patient genetic analysis from different schwannomas indicated inactivation of both the SMARCB1 and NF2 genes. Schwannomatosis is known to be a genetic disorder. However, familial occurrence is inexplicably rare.
771:
MacCollin M, Chiocca EA, Evans DG, Friedman JM, Horvitz R, Jaramillo D, Lev M, Mautner VF, Niimura M, Plotkin SR, Sang CN, Stemmer-Rachamimov A, Roach ES (June 2005). "Diagnostic criteria for schwannomatosis".
279:
If feasible, the schwannomas can be surgically removed. Any tumor-associated pain usually subsides after tumor removal. Damaged nerves and scar tissue can be a result of surgery and pain can be an ongoing
142:. However, molecular analysis of the NF2 gene in schwannomatosis patients has shown the presence of inactivating mutations in the tumor cells, but no evidence of the germline mutations that are found in
607:
Westhout FD, Mathews M, Paré LS, Armstrong WB, Tully P, Linskey ME (June 2007). "Recognizing schwannomatosis and distinguishing it from neurofibromatosis type 1 or 2".
341:
About 1/3 of patients have segmental schwannomatosis, which means that the schwannomas are limited to a single part of the body, such as an arm, a leg or the spine.
222:
Age <30 and ≥2 nonintradermal schwannomas, at least one with histologic confirmation and no evidence of vestibular tumor on MRI scan and no known NF mutation, or
693:
Lunsford LD, Niranjan A, Flickinger JC, Maitz A, Kondziolka D (January 2005). "Radiosurgery of vestibular schwannomas: summary of experience in 829 cases".
1196:
1537:
650:
Senchenkov A, Kriegel A, Staren ED, Allison DC (September 2005). "Use of intraoperative ultrasound in excision of multiple schwannomas of the thigh".
138:
1 of the tumor suppressor gene SMARCB1 has been reported in patients with schwannomatosis. It is located on chromosome 22 a short distance from the
1136:
289:
Other than surgery and pain management, there are no other medical treatments available. There are no drugs available to treat schwannomatosis.
225:
Age >45 and ≥2 nonintradermal schwannomas, at least one with histologic confirmation and no symptoms of 8th nerve dysfunction and no NF2, or
286:
If surgery is unfeasible, then pain management will have to be used. Schwannomatosis can sometimes cause severe, untreatable pain over time.
1436:
840:
1572:
914:
442:
Hanemann CO, Evans DG (December 2006). "News on the genetics, epidemiology, medical care and translational research of
Schwannomas".
1731:
162:, hSNF5, or BAF47. SMARCB1 is mutated in additional tumors including malignant brain & kidney tumors in children. It seems that
1690:
536:
Kluwe, L. (2008). Molecular studies on schwannomatosis. In D. Kaufmann (Ed.), Monographs in Human
Genetics (pp. 177-188): Karger.
1562:
996:
1542:
1186:
98:
Schwannomas are mostly benign tumors that commonly occur in individuals with NF2 and schwannomatosis (sometimes called
1166:
594:
Ferner, Rosalie E., Susan M. Huson, and D. Gareth R. Evans. Neurofibromatoses in clinical practice. Springer, 2011.
42:
1595:
205:
Age >30 years and ≥2 nonintradermal schwannomas, at least one with histologic confirmation and no evidence of
143:
262:
One pathologically confirmed nonvestibular schwannoma plus a first degree relative who meets the above criteria.
1387:
1309:
1304:
1224:
984:
851:
272:
Schwannomatosis patients represent 2.4% to 5% of patients undergoing surgical resection of their schwannomas.
1367:
1341:
728:
MacCollin M, Woodfin W, Kronn D, Short MP (April 1996). "Schwannomatosis: a clinical and pathologic study".
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127:
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cells that myelinate the axons of nerve cells. Myelin is a lipid covering that speeds the conduction of
548:"Evidence of a four-hit mechanism involving SMARCB1 and NF2 in schwannomatosis-associated schwannomas"
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There are several cases where people with schwannomatosis have developed a vestibular schwannoma (
1600:
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1001:
979:
797:
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675:
632:
577:
467:
396:
236:. Diagnosed as definite or possible but limited to one limb or ≤5 contiguous segments of spine.
304:. Success rates, although limited in data, appear to be in the low to mid ninety percent range.
1670:
1552:
1522:
1501:
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1447:
1362:
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1316:
1211:
1131:
1075:
1038:
1023:
964:
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667:
624:
569:
516:
459:
388:
151:
131:
111:
99:
84:
55:
1372:
1357:
1234:
1109:
1065:
781:
737:
702:
659:
616:
559:
506:
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451:
380:
345:
206:
139:
80:
706:
485:
Hulsebos TJ, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P (April 2007).
1700:
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1491:
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1414:
1409:
1353:
1331:
1028:
974:
954:
159:
88:
351:
Patients with schwannomatosis do not have learning disabilities related to the disease.
17:
1532:
1486:
1299:
1229:
1048:
785:
511:
486:
296:
Recently, many advances are being made in the treatment of schwannomas. Of interest is
168:
167:
exhibited a novel germline deletion of the SMARCB1, because most SMARCB1 mutations are
1725:
1615:
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1201:
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Symptoms are sometimes brought on by hormonal changes such as puberty and pregnancy.
163:
103:
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400:
1680:
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636:
322:
150:
schwannomatosis gene(s) in most cases. This is because one study found no SMARCB1
856:
620:
1479:
1424:
1321:
1176:
1151:
969:
92:
1567:
1452:
1419:
1191:
1141:
1126:
1121:
1114:
1099:
1089:
455:
212:
One nonvestibular schwannoma plus a first-degree relative with schwannomatosis
1640:
1382:
1377:
1241:
1219:
1094:
1058:
245:
793:
714:
671:
628:
573:
520:
463:
392:
196:
749:
741:
384:
1146:
923:
875:
371:
Ruggieri M, Huson SM (April 1999). "The neurofibromatoses. An overview".
332:
Multiple schwannomas manifest throughout the body or in isolated regions.
60:
820:
130:
that regulates cell cycle, growth and differentiation. An inactivating
1625:
1085:
1053:
946:
564:
547:
301:
228:
Nonvestibular schwannoma and first-degree relative with schwannomatosis
123:
663:
546:
Sestini R, Bacci C, Provenzano A, Genuardi M, Papi L (February 2008).
832:
502:
107:
416:"Your Guide to Understanding Genetic Conditions: Schwannomatosis"
335:
The schwannomas develop on cranial, spinal and peripheral nerves.
845:
283:
Sometimes, a tumor will reappear at the same site after surgery.
135:
896:
487:"Germline mutation of INI1/SMARCB1 in familial schwannomatosis"
338:
Chronic pain, and sometimes numbness, tingling and weakness.
892:
317:
Many of the symptoms of schwannomatosis overlap with NF2.
188:
Schwannomatosis can be tested prenatally on the NHS.
810:
1583:
1521:
1282:
1210:
1165:
1074:
945:
930:
866:
814:
54:
35:
293:further treatment) with gamma knife radiosurgery.
325:that are hallmarks of neurofibromatosis Type 1 (
602:
600:
437:
435:
908:
8:
91:patients, it consists of multiple cutaneous
83:closely related to the more-common disorder
1197:Reproductive endocrinology and infertility
942:
915:
901:
893:
811:
122:The candidate schwannomatosis gene, named
65:
41:
32:
1538:Bachelor of Medicine, Bachelor of Surgery
563:
510:
209:on MRI scan and no known NF mutation, or
532:
530:
363:
707:10.3171/jns.2005.102.s_supplement.0195
7:
1676:
1437:Physical medicine and rehabilitation
1686:
1573:Medical Scientist Training Program
786:10.1212/01.WNL.0000163982.78900.AD
25:
321:Schwannomas occur instead of the
1705:
1695:
1685:
1675:
1666:
1665:
414:NIH, Genetics Home Reference -.
1706:
251:No evidence of vestibular tumor
87:(NF). Originally described in
1563:Doctor of Osteopathic Medicine
997:Oral and maxillofacial surgery
1:
240:Another set of criteria are:
1543:Bachelor of Medical Sciences
1310:Neurosurgical anesthesiology
621:10.1097/BSD.0b013e318033ee0f
244:Two or more nonintradermal (
1748:
50:Micrograph of a schwannoma
1661:
456:10.1007/s00415-006-0347-0
158:SMARCB1 is also known as
49:
40:
1732:Nervous system neoplasia
1497:Transplantation medicine
1388:Clinical neurophysiology
1305:Obstetric anesthesiology
1225:Interventional radiology
985:Digestive system surgery
18:Neurofibromatosis type 3
1368:Intensive care medicine
1342:Mass gathering medicine
1187:Maternal–fetal medicine
420:Genetics Home Reference
960:Cardiothoracic surgery
254:No known NF-2 mutation
1611:Personalized medicine
1470:Reproductive medicine
1395:Occupational medicine
1349:Evolutionary medicine
742:10.1212/wnl.46.4.1072
385:10.1007/s100720050017
128:tumor suppressor gene
79:is an extremely rare
27:Rare genetic disorder
1631:Traditional medicine
1591:Alternative medicine
1458:Addiction psychiatry
1272:Transfusion medicine
1267:Medical microbiology
1182:Gynecologic oncology
1034:Reproductive surgery
609:J Spinal Disord Tech
1653:History of medicine
1636:Veterinary medicine
1443:Preventive medicine
1295:Adolescent medicine
1137:Infectious diseases
1601:Molecular oncology
1558:Doctor of Medicine
1548:Master of Medicine
1465:Radiation oncology
1337:Emergency medicine
1290:Addiction medicine
1257:Clinical chemistry
1252:Clinical pathology
1044:Transplant surgery
1002:Orthopedic surgery
980:Colorectal surgery
867:External resources
565:10.1002/humu.20679
300:, manufactured by
152:germinal mutations
1719:
1718:
1553:Master of Surgery
1517:
1516:
1502:Tropical medicine
1448:Prison healthcare
1363:Hospital medicine
1327:Disaster medicine
1317:Aviation medicine
1132:Hospital medicine
1039:Surgical oncology
1024:Pediatric surgery
1018:
965:Endocrine surgery
890:
889:
664:10.1002/jcu.20161
652:J Clin Ultrasound
491:Am. J. Hum. Genet
373:Ital J Neurol Sci
132:germline mutation
112:action potentials
100:neurofibromatosis
85:neurofibromatosis
74:
73:
30:Medical condition
16:(Redirected from
1739:
1709:
1708:
1699:
1689:
1688:
1679:
1678:
1669:
1668:
1373:Medical genetics
1358:General practice
1235:Nuclear medicine
1110:Gastroenterology
1066:Vascular surgery
1016:
943:
917:
910:
903:
894:
812:
806:
805:
768:
762:
761:
725:
719:
718:
701:(Suppl): 195–9.
690:
684:
683:
647:
641:
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604:
595:
592:
586:
585:
567:
543:
537:
534:
525:
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476:
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411:
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346:acoustic neuroma
207:vestibular tumor
81:genetic disorder
70:
69:
45:
33:
21:
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1746:
1742:
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1722:
1721:
1720:
1715:
1657:
1646:Chief physician
1579:
1524:
1513:
1507:Travel medicine
1492:Sports medicine
1475:Sexual medicine
1415:Palliative care
1410:Pain management
1354:Family medicine
1332:Diving medicine
1278:
1206:
1168:
1161:
1077:
1070:
1029:Plastic surgery
975:General surgery
955:Cardiac surgery
936:
934:
926:
921:
891:
886:
885:
862:
861:
823:
809:
780:(11): 1838–45.
770:
769:
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692:
691:
687:
649:
648:
644:
606:
605:
598:
593:
589:
545:
544:
540:
535:
528:
484:
483:
479:
450:(12): 1533–41.
441:
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433:
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422:
413:
412:
408:
370:
369:
365:
361:
315:
269:
194:
186:
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77:Schwannomatosis
64:
36:Schwannomatosis
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28:
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15:
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1584:Related topics
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1230:Neuroradiology
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1167:Obstetrics and
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1049:Trauma surgery
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1036:
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1021:
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1019:
1012:Otolaryngology
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987:
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938:subspecialties
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1616:Public health
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1599:
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1596:Allied health
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1408:
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1405:Oral medicine
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1400:Ophthalmology
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1262:Cytopathology
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1209:
1203:
1202:Urogynecology
1200:
1198:
1195:
1193:
1190:
1188:
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1180:
1178:
1175:
1174:
1172:
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1158:
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1130:
1128:
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1105:Endocrinology
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1101:
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1091:
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1083:
1081:
1079:
1073:
1067:
1064:
1060:
1057:
1056:
1055:
1052:
1050:
1047:
1045:
1042:
1040:
1037:
1035:
1032:
1030:
1027:
1025:
1022:
1015:
1014:
1013:
1010:
1008:
1005:
1003:
1000:
998:
995:
993:
990:
986:
983:
981:
978:
977:
976:
973:
971:
968:
966:
963:
961:
958:
956:
953:
952:
950:
948:
944:
941:
939:
933:
929:
925:
918:
913:
911:
906:
904:
899:
898:
895:
882:
878:
877:
873:
872:
869:
865:
858:
854:
853:
849:
847:
843:
842:
838:
835:
834:
830:
826:
825:
822:
817:
813:
803:
799:
795:
791:
787:
783:
779:
775:
767:
764:
759:
755:
751:
747:
743:
739:
736:(4): 1072–9.
735:
731:
724:
721:
716:
712:
708:
704:
700:
696:
689:
686:
681:
677:
673:
669:
665:
661:
657:
653:
646:
643:
638:
634:
630:
626:
622:
618:
615:(4): 329–32.
614:
610:
603:
601:
597:
591:
588:
583:
579:
575:
571:
566:
561:
558:(2): 227–31.
557:
553:
549:
542:
539:
533:
531:
527:
522:
518:
513:
508:
504:
500:
497:(4): 805–10.
496:
492:
488:
481:
478:
473:
469:
465:
461:
457:
453:
449:
445:
438:
436:
432:
421:
417:
410:
407:
402:
398:
394:
390:
386:
382:
379:(2): 89–108.
378:
374:
367:
364:
358:
353:
350:
347:
343:
340:
337:
334:
331:
328:
324:
323:neurofibromas
320:
319:
318:
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306:
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299:
295:
291:
288:
285:
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278:
274:
271:
270:
266:
261:
260:
259:
253:
250:
248:) schwannomas
247:
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227:
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199:
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183:
178:
176:
174:
170:
165:
164:heterozygotes
161:
156:
153:
147:
145:
141:
137:
133:
129:
125:
117:
115:
113:
109:
105:
104:Schwann cells
101:
96:
94:
90:
86:
82:
78:
68:
62:
59:
57:
53:
48:
44:
39:
34:
19:
1621:Rural health
1606:Nanomedicine
1157:Rheumatology
1088: /
1007:Hand surgery
992:Neurosurgery
874:
850:
839:
827:
777:
773:
766:
733:
729:
723:
698:
695:J. Neurosurg
694:
688:
658:(7): 360–3.
655:
651:
645:
612:
608:
590:
555:
551:
541:
494:
490:
480:
447:
443:
423:. Retrieved
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148:
121:
97:
76:
75:
1691:Wikiproject
1480:Venereology
1425:Neonatology
1322:Dermatology
1177:Gynaecology
1169:gynaecology
1152:Pulmonology
970:Eye surgery
932:Specialties
102:type III).
93:schwannomas
1453:Psychiatry
1439:(PM&R)
1432:Phlebology
1420:Pediatrics
1247:Anatomical
1212:Diagnostic
1192:Obstetrics
1142:Nephrology
1127:Hematology
1122:Geriatrics
1115:Hepatology
1100:Cardiology
1090:Immunology
552:Hum. Mutat
425:2019-01-03
359:References
298:CyberKnife
173:frameshift
146:patients.
1641:Physician
1525:education
1383:Neurology
1378:Narcology
1242:Pathology
1220:Radiology
1095:Angiology
1059:Andrology
774:Neurology
730:Neurology
444:J. Neurol
313:Prognosis
308:benefits.
276:incision.
267:Treatment
246:cutaneous
234:Segmental
192:Postnatal
179:Diagnosis
56:Specialty
1726:Category
1671:Category
1147:Oncology
1078:medicine
1076:Internal
924:Medicine
876:Orphanet
802:10502093
794:15955931
758:20500367
715:15662809
680:32230328
672:16196005
629:17538359
582:26081790
574:18072270
521:17357086
472:11854280
464:17219030
401:11471989
393:10933430
280:problem.
218:Possible
201:Definite
184:Prenatal
140:NF2 gene
89:Japanese
61:Oncology
1711:Outline
1681:Commons
1626:Therapy
1523:Medical
1086:Allergy
1054:Urology
947:Surgery
857:C536641
836:: Q85.0
750:8780094
637:8221625
512:1852715
302:Accuray
126:, is a
124:SMARCB1
1701:Portal
1568:MD–PhD
846:162091
800:
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756:
748:
713:
678:
670:
635:
627:
580:
572:
519:
509:
470:
462:
399:
391:
63:
1283:Other
881:93921
798:S2CID
754:S2CID
676:S2CID
633:S2CID
578:S2CID
468:S2CID
397:S2CID
169:point
118:Cause
108:glial
852:MeSH
841:OMIM
790:PMID
746:PMID
711:PMID
668:PMID
625:PMID
570:PMID
517:PMID
460:PMID
389:PMID
160:INI1
136:exon
106:are
1017:ENT
935:and
829:ICD
782:doi
738:doi
703:doi
699:102
660:doi
617:doi
560:doi
507:PMC
499:doi
452:doi
448:253
381:doi
327:NF1
258:or
171:or
144:NF2
134:in
1728::
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879::
855::
844::
833:10
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788:.
778:64
776:.
752:.
744:.
734:46
732:.
709:.
697:.
674:.
666:.
656:33
654:.
631:.
623:.
613:20
611:.
599:^
576:.
568:.
556:29
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550:.
529:^
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505:.
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489:.
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395:.
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740::
717:.
705::
682:.
662::
639:.
619::
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562::
523:.
501::
474:.
454::
428:.
403:.
383::
20:)
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