Abstract
Idiopathic superior oblique muscle palsy presents, as quantitative phenotypes, vertical deviation and cyclodeviation in eye alignment on clinical testing, and superior oblique muscle hypoplasia on imaging. We determined ARIX and PHOX2B polymorphisms as genotypes, and analyzed phenotype–phenotype and genotype–phenotype correlations in 37 patients with idiopathic superior oblique muscle palsy. Vertical deviations were measured at upright position of the head and head tilt for 30° to either side, and angles of objective excyclodeviations were determined by image analysis on fundus photographs. Cross-sectional areas of the superior oblique muscle near the eye globe-optic nerve junction were measured by image analysis on coronal sections of magnetic resonance imaging to calculate the paretic-side/normal-side ratios. Among the phenotypes, the increase in vertical deviations elicited by head tilt to the paretic side, the decrease in vertical deviations elicited by head tilt to the normal side and the difference of angles of objective excyclodeviations between the paretic side and normal side were significantly correlated inversely with the paretic-side/normal-side ratios of the cross-sectional areas of the muscle (r=−0.43 with P=0.0084, r=−0.34 with P=0.038, and r=−0.43 with P=0.009, respectively, n=37, Pearson's correlation test). Fifteen patients with ARIX and/or PHOX2B polymorphisms had significantly greater paretic-side/normal-side ratios of the muscle compared with 20 patients without the polymorphisms (P=0.017, n=35, Mann–Whitney U-test). The patients with ARIX and/or PHOX2B polymorphisms had less hypoplastic superior oblique muscles.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Bhola, R. M., Horne, G. V., Squirrell, D. M., Chan, T. K. & Kumar, D. Autosomal dominant congenital superior oblique palsy. Eye 15, 479–484 (2001).
Botelho, P. J. & Giangiacomo, J. G. Autosomal-dominant inheritance of congenital superior oblique palsy. Ophthalmology 103, 1508–1511 (1996).
Harris Jr, D. J., Memmen, J. E., Katz, N. N. & Parks, M. M. Familial congenital superior oblique palsy. Ophthalmology 93, 88–90 (1986).
Astle, W. F. & Rosenbaum, A. L. Familial congenital fourth cranial nerve palsy. Arch. Ophthalmol. 103, 532–535 (1985).
Imai, S., Matsuo, T., Itoshima, E. & Ohtsuki, H. Clinical features, ARIX and PHOX2B nucleotide changes in three families with congenital superior oblique muscle palsy. Acta Med. Okayama 62, 45–53 (2008).
Sawa, M. Absence of the right superior oblique muscle: a case report. Jpn. J. Ophthalmol. 22, 178–183 (1978).
Matsuo, T., Ohtsuki, H., Sogabe, Y., Konishi, H., Takenawa, K. & Watanabe, Y. Vertical abnormal retinal correspondence in three patients with congenital absence of the superior oblique muscle. Am. J. Ophthalmol. 106, 341–345 (1988).
Helveston, E. M., Krach, D., Plager, D. A. & Ellis, F. D. A new classification of superior oblique palsy based on congenital variations in the tendon. Ophthalmology 99, 1609–1615 (1992).
Plager, D. A. Tendon laxity in superior oblique palsy. Ophthalmology 99, 1032–1038 (1992).
Demer, J. L. & Miller, J. M. Magnetic resonance imaging of the functional anatomy of the superior oblique muscle. Invest. Ophthalmol. Vis. Sci. 36, 906–913 (1995).
Sato, M. Magnetic resonance imaging and tendon anomaly associated with congenital superior oblique palsy. Am. J. Ophthalmol. 127, 379–387 (1999).
Chan, T. K. & Demer, J. L. Clinical features of congenital absence of the superior oblique muscle as demonstrated by orbital imaging. J. AAPOS 3, 143–150 (1999).
Sato, M., Iwata, E. A., Takai, Y., Hikoya, A. & Koide, Y. M. Superior oblique palsy with class III tendon anomaly. Am. J. Ophthalmol. 146, 385–394 (2008).
Uchiyama, E., Matsuo, T., Imai, S. & Itoshima, E. Paretic side/normal side ratios of cross-sectional areas of the superior oblique muscle vary largely in idiopathic superior oblique palsy. Am. J. Ophthalmol. 149, 508–512 (2010).
Engle, E. C. Genetic basis of congenital strabismus. Arch. Ophthalmol. 125, 189–195 (2007).
Yamada, K., Andrews, C., Chan, W. M., McKeown, C. A., Magli, A., De Berardinis, T. et al. Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type1(CFEOM1). Nat. Genet. 35, 318–321 (2003).
Nakano, M., Yamada, K., Fain, J., Sener, E. C., Selleck, C. J., Awad, A. H. et al. Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of the extraocular muscles type 2. Nat. Genet. 29, 315–320 (2001).
Jiang, Y., Matsuo, T., Fujiwara, H., Hasebe, S., Ohtsuki, H. & Yasuda, T. ARIX gene polymorphisms in patients with congenital superior oblique muscle palsy. Br. J. Ophthalmol. 88, 263–267 (2004).
Jiang, Y., Matsuo, T., Fujiwara, H., Hasebe, S., Ohtsuki, H. & Yasuda, T. ARIX and PHOX2B polymorphisms in patients with congenital superior oblique muscle palsy. Acta Med. Okayama 59, 55–62 (2005).
Pattyn, A., Morin, X., Cremer, H., Goridis, C. & Brunet, J F. Expression and interactions of the two closely related homeobox genes Phox2a and Phox2b during neurogenesis. Development 124, 4065–4075 (1997).
Horikawa, A., Hirai, Y., Kono, R., Hasebe, S. & Ohtsuki, H. Evaluation of cyclodeviation by scanning laser ophthalmoscope. Comparison of subjective and objective cyclodeviation in vertical strabismus. (in Japanese). Rinsho Ganka (Jpn. J. Clin. Ophthalmol.) 54, 85–88 (2000).
Horikawa, A., Hirai, Y., Kono, R., Hasebe, S. & Ohtsuki, H. Sensory adaptation to cyclodeviations in superior oblique palsy. (in Japanese). Rinsho Ganka (Jpn. J. Clin. Ophthalmol.) 54, 1447–1450 (2000).
Bixenman, W. W. & von Noorden, G. K. Apparent foveal displacement in normal subjects and in cyclotropia. Ophthalmology 89, 58–62 (1982).
Demer, J. L., Miller, J. M., Koo, E. Y. & Rosenbaum, A. L. Quantitative magnetic resonance morphometry of extraocular muscles: a new diagnostic tool in paralytic strabismus. J. Pediatr. Ophthalmol. Strabismus 31, 177–188 (1994).
Kushner, B. J. Errors in the three-step test in the diagnosis of vertical strabismus. Ophthalmology 96, 127–132 (1989).
Hamasaki, I., Hasebe, S., Furuse, T. & Ohtsuki, H. Relationship between static ocular counterroll and Bielschowsky head tilt phenomenon. Invest. Ophthalmol. Vis. Sci. 51, 201–206 (2010).
Kono, R., Okanobu, H., Ohtsuki, H. & Demer, J. L. Absence of relationship between oblique muscle size and Bielschowsky head tilt phenomenon in clinically diagnosed superior oblique palsy. Invest. Ophthalmol. Vis. Sci. 50, 175–179 (2009).
Ohtsuki, H., Hasebe, S., Kono, R., Yamane, T., Fujiwara, H. & Shiraga, F. Large Bielschowsky head-tilt phenomenon and inconspicuous vertical deviation in the diagnostic positions in congenital superior oblique palsy. Am. J. Ophthalmol. 130, 854–856 (2000).
Kushner, B. J. The influence of head tilt on ocular torsion in patients with superior oblique muscle palsy. . J. AAPOS 13, 132–135 (2009).
Kono, R., Okanobu, H., Ohtsuki, H. & Demer, J. L. Displacement of the rectus muscle pulleys simulating superior oblique palsy. . Jpn. J. Ophthalmol. 52, 36–43 (2008).
Kushner, B. J. Incomitant strabismus. Does extraocular muscle form denote function? Arch. Ophthalmol. 128, 1604–1609 (2010).
Acknowledgements
This study was supported in part by a grant-in-aid for scientific research from the Ministry of Education, Science, Sports, Culture, and Technology of Japan (No. 22591964).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ohkubo, S., Matsuo, T., Hasebe, K. et al. Phenotype–phenotype and genotype–phenotype correlations in patients with idiopathic superior oblique muscle palsy. J Hum Genet 57, 122–129 (2012). https://doi.org/10.1038/jhg.2011.138
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/jhg.2011.138
Keywords
This article is cited by
-
Trochlear nerve agenesis in a patient with 18q22.2q23 deletion
Neurological Sciences (2024)
-
Clinical factors underlying a single surgery or repetitive surgeries to treat superior oblique muscle palsy
SpringerPlus (2015)
