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DOI: 10.1055/s-0041-100772
Kongenitale kraniale Dysinnervationssyndrome (CCDD)
Congenital Cranial Dysinnervation Disorders (CCDD)Publikationsverlauf
eingereicht 02. Januar 2015
akzeptiert 05. Februar 2015
Publikationsdatum:
24. März 2015 (online)
![](https://www.thieme-connect.de/media/klimo/201503/lookinside/thumbnails/10.1055-s-0041-100772-1.jpg)
Zusammenfassung
Genetische Untersuchungen in der Augenheilkunde haben in den vergangenen Jahren das Wissen über hereditäre Augenerkrankungen wesentlich erweitert und zu einer auf genetischen Befunden basierenden Neueinteilung einer Reihe von Krankheitsbildern geführt. Die früher als „kongenitale Fibrosesyndrome“ bezeichneten Schielsyndrome, welche durch eine nicht progrediente restriktive Störung der Okulomotorik mit oder ohne zusätzliche Oberlidptosis gekennzeichnet sind, werden nun unter dem Begriff „Congenital Cranial Dysinnervation Disorders“ (CCDDs) zusammengefasst. Die ursächliche Störung liegt in einer fehlerhaften Innervation der Muskeln aufgrund einer Fehlentwicklung der Kerngebiete der entsprechenden Hirnnerven im Hirnstamm und Pons, und nicht – wie früher angenommen – in einer primären Fibrose der extraokularen Muskeln. In dieser Arbeit werden die kongenitale Fibrose der äußeren Augenmuskeln (CFEOM), das Duane-Syndrom, die horizontale Blickparese mit progredienter Skoliose, die kongenitale Ptosis und das Möbius-Syndrom vorgestellt sowie Grundzüge intrazellulärer Transportmechanismen und der Kinesine erläutert.
Abstract
Knowledge about hereditary eye diseases has been substantially increased by means of genetic testing during the last decade. This has resulted in a new classification of a number of disease patterns, which are characterised by non-progressive restrictive disorders of the oculomotor system, formerly classified as “congenital fibrosis syndromes”. Based on the results of genetic testing, these ocular motility disorders are now referred to as “congenital cranial dysinnervation disorders” (CCDDs). They are caused by an impaired innervation of extraocular muscles because of a dysgenesis of the nuclei of the affected cranial nerves in the brainstem and pons and not by primary fibrosis of the extraocular muscles. In this review, congenital fibrosis of the extraocular muscles (CFEOM), Duane syndrome, horizontal gaze palsy with progressive scoliosis, congenital ptosis and Moebius syndrome are presented and basic principles of intracellular transport mechanisms and kinesins are discussed.
Schlüsselwörter
Genetik - Strabologie - kongenitale kraniale Dysinnervationssyndrome - CFEOM - Duane-Syndrom - KinesineKey words
genetics - strabism - congenital cranial dysinnervation disorders - CFEOM - Duane syndrome - kinesins* Dr. M. M. Nentwich und Dr. M. F. Nentwich haben in gleicher Weise zu dieser Arbeit beigetragen.
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Literatur
- 1 Engle EC. Applications of molecular genetics to the understanding of congenital ocular motility disorders. Ann N Y Acad Sci 2002; 956: 55-63
- 2 Flaherty MP, Grattan-Smith P, Steinberg A et al. Congenital fibrosis of the extraocular muscles associated with cortical dysplasia and maldevelopment of the basal ganglia. Ophthalmology 2001; 108: 1313-1322
- 3 Gutowski NJ, Bosley TM, Engle EC. 110th ENMC International Workshop: the congenital cranial dysinnervation disorders (CCDDs). Naarden, The Netherlands, 25–27 October, 2002. Neuromuscul Disord 2003; 13: 573-578
- 4 Ellis FJ, Jeffery AR, Seidman DJ et al. Possible association of congenital Brown syndrome with congenital cranial dysinnervation disorders. J AAPOS 2012; 16: 558-564
- 5 Traboulsi EI. Congenital cranial dysinnervation disorders and more. J AAPOS 2007; 11: 215-217
- 6 Rudolph G, Nentwich M, Hellebrand H et al. KIF21A variant R954 W in familial or sporadic cases of CFEOM1. Eur J Ophthalmol 2009; 19: 667-674
- 7 Roggenkaemper P. General fibrosis syndrome. Proceedings of the International Symposium on Strabismus and Amblyopia. Tel Aviv, Israel: Acta Strabologica; 1985: 241-246
- 8 Graeber CP, Hunter DG, Engle EC. The genetic basis of incomitant strabismus: consolidation of the current knowledge of the genetic foundations of disease. Semin Ophthalmol 2013; 28: 427-437
- 9 Parsa CF, Grant PE, Dillon jr. WP et al. Absence of the abducens nerve in Duane syndrome verified by magnetic resonance imaging. Am J Ophthalmol 1998; 125: 399-401
- 10 DeRespinis PA, Caputo AR, Wagner RS et al. Duaneʼs retraction syndrome. Surv Ophthalmol 1993; 38: 257-288
- 11 Nentwich MF. Molekulargenetische Untersuchungen zur kongenitalen Fibrose der extraokulären Muskeln Typ 1 (CFEOM1) [Dissertation]. München: Medizinische Fakultät der Ludwig-Maximilians-Universität; 2009
- 12 Barry JS, Reddy MA. The association of an epibulbar dermoid and Duane syndrome in a patient with a SALL1 mutation (Townes-Brocks Syndrome). Ophthalmic Genet 2008; 29: 177-180
- 13 Appukuttan B, Gillanders E, Juo SH et al. Localization of a gene for Duane retraction syndrome to chromosome 2q31. Am J Hum Genet 1999; 65: 1639-1646
- 14 Reck AC, Manners R, Hatchwell E. Phenotypic heterogeneity may occur in congenital fibrosis of the extraocular muscles. Br J Ophthalmol 1998; 82: 676-679
- 15 Heuck G. Ueber angeborenen vererbten Beweglichkeitsdefect der Augen. Klin Monatsbl Augenheilkd 1879; 17: 253-278
- 16 Laughlin RC. Congenital fibrosis of the extraocular muscles; a report of six cases. Am J Ophthalmol 1956; 41: 432-438
- 17 Brown HW. Congenital Muscle Abnormalities. In: Allen JH, ed. Strabismus Ophthalmic Symposium. St. Louis: Mosby; 1950: 229-233
- 18 Harley RD, Rodrigues MM, Crawford JS. Congenital fibrosis of the extraocular muscles. J Pediatr Ophthalmol Strabismus 1978; 15: 346-358
- 19 Al-Mujaini A. Congenital fibrosis of the extraocular muscles. Oman J Ophthalmol 2010; 3: 160-161
- 20 Merino P, Gómez de Liaño P, Fukumitsu H et al. Congenital fibrosis of the extraocular muscles: magnetic resonance imaging findings and surgical treatment. Strabismus 2013; 21: 183-189
- 21 Yamada K, Andrews C, Chan WM et al. Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). Nat Genet 2003; 35: 318-321
- 22 Engle EC, Goumnerov BC, McKeown CA et al. Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles. Ann Neurol 1997; 41: 314-325
- 23 Rudolph G, Nentwich MF. Congenitale Fibrosesyndrome der extraokulären Muskeln. Der Augenspiegel 2010; 07–08: 38-39
- 24 Sener EC, Taylan Sekeroglu H, Ural O et al. Strabismus surgery in congenital fibrosis of the extraocular muscles: a paradigm. Ophthalmic Genet 2014; 35: 208-225
- 25 Khan AO, Almutlaq M, Oystreck DT et al. Retinal dysfunction in patients with congenital fibrosis of the extraocular muscles type 2. Ophthalmic Genet Epub ahead of print June 18, 2014
- 26 Nakano M, Yamada K, Fain J et al. Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of the extraocular muscles type 2. Nat Genet 2001; 29: 315-320
- 27 Tischfield MA, Baris HN, Wu C et al. Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell 2010; 140: 74-87
- 28 Dos Santos AV, Matias S, Saraiva P et al. MR imaging features of brain stem hypoplasia in familial horizontal gaze palsy and scoliosis. AJNR Am J Neuroradiol 2006; 27: 1382-1383
- 29 Jen JC, Chan WM, Bosley TM et al. Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis. Science 2004; 304: 1509-1513
- 30 Arlt EM, Keindl TK, Grabner G et al. Horizontale Blickparese mit progredienter Skoliose. Klin Monatsbl Augenheilkd 2015; 232: 281-282
- 31 Engle EC, Castro AE, Macy ME et al. A gene for isolated congenital ptosis maps to a 3-cM region within 1p32–p34.1. Am J Hum Genet 1997; 60: 1150-1157
- 32 McMullan TF, Collins AR, Tyers AG et al. A novel X-linked dominant condition: X-linked congenital isolated ptosis. Am J Hum Genet 2000; 66: 1455-1460
- 33 McMullan TW, Crolla JA, Gregory SG et al. A candidate gene for congenital bilateral isolated ptosis identified by molecular analysis of a de novo balanced translocation. Hum Genet 2002; 110: 244-250
- 34 Wu SQ, Man FY, Jiao YH et al. Magnetic resonance imaging findings in sporadic Möbius syndrome. Chin Med J (Engl ) 2013; 126: 2304-2307
- 35 Dumars S, Andrews C, Chan WM et al. Magnetic resonance imaging of the endophenotype of a novel familial Möbius-like syndrome. J AAPOS 2008; 12: 381-389
- 36 Tawfik HA, Rashad MA. Surgical management of hypotropia in congenital fibrosis of extraocular muscles (CFEOM) presented by pseudoptosis. Clin Ophthalmol 2013; 7: 1-6
- 37 Roggenkämper P, Mertz M. Range of variation of clinical forms of congenital familial motility disorders. Fortschr Ophthalmol 1984; 81: 385-387
- 38 Cooymans P, Al-Zuhaibi S, Al-Senawi R et al. Congenital fibrosis of the extraocular muscles. Oman J Ophthalmol 2010; 3: 70-74
- 39 Ebbing B. The molecular motor kinesin: From single-molecule mechanisms to joint action [Dissertation]. München: Fakultät für Biologie, Ludwig-Maximilians-Universität München; 2008
- 40 Hirokawa N, Noda Y. Intracellular transport and kinesin superfamily proteins, KIFs: structure, function, and dynamics. Physiol Rev 2008; 88: 1089-1118
- 41 Hirokawa N, Takemura R. Molecular motors in neuronal development, intracellular transport and diseases. Curr Opin Neurobiol 2004; 14: 564-573
- 42 Marszalek JR, Weiner JA, Farlow SJ et al. Novel dendritic kinesin sorting identified by different process targeting of two related kinesins: KIF21A and KIF21B. J Cell Biol 1999; 145: 469-479
- 43 Cheng L, Desai J, Miranda CJ et al. Human CFEOM1 mutations attenuate KIF21A autoinhibition and cause oculomotor axon stalling. Neuron 2014; 82: 334-349
- 44 Van der Vaart B, van Riel WE, Doodhi H et al. CFEOM1-associated kinesin KIF21A is a cortical microtubule growth inhibitor. Dev Cell 2013; 27: 145-160