Autosomal-dominant Inheritance of Congenital Superior Oblique Palsy

Autosomal--dominant Inheritance of Congenital Superior Oblique Palsy Paul]. Botelho, MD, Joseph G. Giangiacomo, MD Purpose: A pedigree comprised of five affected members is presented to demonstrate the genetic transmission of congenital superior oblique palsy. Methods: A 2-year-old boy referred for strabismus was found to have bilateral congenital superior oblique palsy. The authors subsequently performed a complete ophthalmologic examination on all available family members to determine the inheritance pattern. The diagnosis of congenital superior oblique palsy was based on results of prism cover testing, ductions, and the Bielschowsky head tilt test, in addition to a history of early onset of symptoms and absence of preceding head trauma. Results: The father, paternal grandfather, and a brother of the 2-year-old boy were found to have bilateral congenital superior oblique palsy. Evaluation of the paternal aunt showed right congenital superior oblique palsy. Bilateral absence of the superior oblique tendon was noted at the time of surgery in the 2-year-old boy. Conclusion: The occurrence of genetic transmission by an autosomal-dominant mode should be considered in patients with congenital superior oblique palsy. Ophthalmology 1996; 103: 1508-1511

Superior oblique palsy is the most common isolated cranial nerve weakness encountered in ophthalmology. I Congenital superior oblique palsy accounts for a large percentage of all patients with isolated cranial nerve weakness, ranging from 29% to 67%.2-4 The occurrence of congenital superior oblique palsy usually is sporadic. In fact, a paucity of case reports of familial congenital superior oblique palsy exists in the literature. 5 - 7 A pedigree, the first reported with involvement by examination of three successive generations, is presented to illustrate the genetic transmission of congenital superior oblique palsy. Moreover, the site of pathology responsible for weakness of the superior oblique is known in an affected member of the family. The findings of this pedigree Originally received: October 2, 1995. Revision accepted: May 22, 1996. From the Mason Institute of Ophthalmology, University of MissouriColumbia, Columbia. Presented in part as a poster at the American Academy of Ophthalmology Annual Meeting, Atlanta, Georgia, Oct/Nov, 1995. Supported in part by an unrestricted grant from Research to Prevent ~ Blindness, Inc, New York, New York. Reprint requests to Joseph G. Giangiacomo, MD, Mason Institute of Ophthalmology, University of Missouri-Columbia, One Hospital Dr, Columbia, MO 65212.

1508

are compared with those of prior familial case reports. The pathophysiology and management of congenital superior oblique palsy also are discussed.

Methods We reviewed the records of a 2-year-old boy with bilateral congenital superior oblique palsy. The child's family history was remarkable for strabismus or head tilt, involving several relatives (Fig 1). All available members of the family were evaluated over a 6-month period to establish the inheritance pattern of congenital superior oblique palsy. We performed a complete ophthalmologic examination on six additional family members. Sensory testing included the Worth four-dot test and the Titmus stereo acuity. The diagnosis of superior oblique palsy was based on the results of prism cover testing, ductions, versions, double Maddox rod test, and the three-step test. Typical findings include hypertropia of the involved eye in primary gaze which increases with adduction and a positive three-step test with tilting toward the affected eye. The palsy is presumed to be congenital when given a history of early onset of symptoms and absence of an inciting event.

Botelho and Giangiacomo . Congenital Superior Oblique I Case 5

:II

1II Case 3

Case 1

Figure 1. Ped igree. Closed squares = males with congenital bilateral superior oblique palsy; half-filled circles = females with congenital right superior oblique palsy; hatched squares = males with left head tilt by history only; rings = females who underwent ophthalmologic examination, no strabismus found.

Case Reports Case 1. A 2-year-old white boy was examined for right hyperdeviation noted since birth. The parents reported that the right hypertropia was constant, worse in left gaze, and not accompanied by a head tilt or turn. His birth weight was 4.176 g. The full-term gestation, C-section delivery (mother had had prior C-sections), and postpartum course of the patient all were uncomplicated. His medical history included macrocephaly and developmental delay. A prior computed tomography scan of the head was normal. There was no history of trauma, hydrocephalus, or craniosynostosis. On examination, cycloplegic retinoscopy showed significant with-the-rule astigmatism (refractive error of +.50+ 1.50 axis 085 in the right eye and plano +2.50 axis 100 in the left eye). The results of the sensory and motor examination are summarized in Tables 1 and 2, respectively . Four months after the initial examination, the patient underwent surgical correction of the bilateral superior oblique palsy. The patient had no prior extraocular muscle surgery. On

attempted bilateral superior oblique tuck using a fornix-based incision, the superior oblique tendon could not be identified on either side. Both the nasal and temporal aspects of the superior recti were explored. The inspection did not include disinsertion of the superior recti or dissection beyond the Tenon capsule toward the trochlea. A right inferior oblique recession and left inferior oblique myectomy were performed. Postoperatively, right hypertropia and new-onset left head tilt were found. There was improvement in the " V" pattern horizontal strabismus, but significant overaction of the right inferior oblique persisted. The right inferior oblique muscle subsequently was re-explored. A subtotal extirpation of the right inferior oblique was performed which corrected the right hypertropia and left head tilt. Case 2. The father of the propositus had a 15-year history of intermittent diplopia and longstanding left head tilt. His refractive errors were -1.75 diopters in the right eye and -3 .00 diopters in the left. On examination, best-corrected visual acuities were 20/30 in the right eye and 20/20 in the left. There was no evidence of intraocular or optic nerve pathology. The patient underwent a non contrast computed tomography scan of the orbits. The superior oblique muscle belly was identified and of normal size bilaterally. The status of the trochlea or the superior oblique tendons could not be determined from the scan, however.

Results All affected members of the pedigree are presented (Tables 1 and 2). The brother, father, and paternal grandfather of the propositus were found to have bilateral congenital superior oblique palsy. The paternal aunt of the propositus, however, had right congenital superior oblique palsy on examination. The mother and paternal grandmother of cases 1 and 3, both asymptomatic, had no evidence of strabismus on examination. All patients were noted to have reduced stereo visual acuity, whereas three patients were found to have suppression on Worth four-dot testing. Only case 2 had evidence of anisometropic amblyopia of the right eye.

Table 1. Results of the Sensory Examination and History of all Patients Case No.

2 Age (yrs)/sex Symptoms Age onset (yrs) Head tum Head tilt History of head trauma Medical history

2/M

No No No Macrocephaly

Visual acuity OO(OS)

CSM (CSM)

Excyclotorsion Worth 4-dot test (6 m) Stereo acuity (seconds of arc) CY A

= cardiovascular accident; 0

0

33/M Occasional diplopia Teens No Left No None 20/30 (20/20) 2° Suppression, 00 400

= right eye; OS = left eye;

CSM

4

3

5

50/F 8/M 77/M Occasional diplopia Occasional diplopia None Teens 6 No No No Right Left No No No No None None Atrial fibrillation HTN (no CVA) 20/20 20/20 20/20 (20/20) (20/20) (20/20) 0° 0° r Suppression, OS Fusion Suppression, 00 200 200 60

= central steady and

maintained.

1509

Volume 103, Number 9, September 1996

Ophthalmology

Table 2. Results of the 2-step Test and Motor Examination for all Patients Case No.

Hypertropia in primary (PD) Hypertropia on right gaze (PD) Hypertropia on left gaze (PD) Right head tilt (PD) 3-step test Left head tilt (PD) Underacting superior Oblique OD (OS) Overacting inferior Oblique OD (OS) "V" pattern esotropia Surgery

PO

5

15 right

8 right

Ortho

25 right

8 left

15 left

4 left

14 left

10 right

16 left

10 right

20 right

4 right

45 right

Ortho

10 right

8 right

4 right

30 right

6 right

6 left Yes (yes)

4 left Yes (yes)

8 left Yes (yes)

15 right Yes (no)

12 left Yes (yes)

+4(+2)

+2(+1)

+1 (+3)

+3 (no)

+1 (+1)

Yes

No

Yes

Yes RIO recess LIO Myecto Subtotal RIO extirpation

= prism diopters; OD = right eye;

OS

Yes

= left eye; RIO = right

Discussion Superior oblique palsy is a common cause of vertical strabismus with torticollis. The etiology of congenital superior oblique palsy remains speculative, however. Possible causes include hypoplasia of the trochlear nucleus, trochlear fascicle or nerve injury, and anatomic defects of the superior oblique tendon or the trochlea. 8 Birth trauma with resultant trochlear nerve paresis or palsy has been the prevailing theory.9 Recently, this mechanism has been challenged. 1O Several patients with anatomic abnormalities of the superior oblique tendon or the trochlea as the defect responsible for congenital superior oblique palsy have been reported. 11,12 A series of patients with superior oblique palsy who underwent surgery on the superior oblique tendon showed that in 33 of 36 congenital cases the tendon was found to be anomalous. 10 The authors concluded that the defect responsible for congenital superior oblique palsy is usually anatomic and less often the result of a neurologic event. The cause of the anatomic anomalies found with relative frequency in patients with congenital superior oblique palsy is not clear. Environmental insults responsible for the occurrence of isolated abnormalities of the superior oblique tendon have not been identified. Structural abnormalities of the superior oblique tendon or trochlea or both . have been reported in association with craniosynostosis and Down syndrome.12 ,13 However, the role of genetic defects in the pathogenesis of isolated congenital superior oblique palsy has not been established. Affected members of this pedigree manifest features of congenital superior oblique palsy, including t!arly onset of symptoms and absence of preceding head trauma. Although the paternal grandfather of the propositus was

1510

4

3

2

inferior oblique; LIO

= left

inferior oblique.

asymptomatic, the presence of suppression on visual sensory testing suggests an early onset of the bilateral superior oblique palsy.14 With the exception of case 4, all affected members of the family had bilateral involvement with varying severity. In fact, cases 2, 3, and 5 had subtle findings of bilateral involvement. Findings suggestive of bilateral superior oblique palsy include a positive Bielschowsky head tilt test to both sides and' 'V" pattern esotropia. 15 These findings, in addition to the ductions, helped to establish bilateral involvement in these patients with subtle findings. In the 2-year-old boy, the superior oblique tendons were not found at the time of surgery. Preoperative findings that suggest the absence of the superior oblique tendon include large horizontal strabismus, significant underaction of the superior oblique tendon, amblyopia, and vertical anomalous retinal correspondence. 11 , 16 Case 1 was found to have significant bilateral superior oblique underaction and horizontal strabismus. Helveston and associates 10 believed that the absence of the superior oblique tendon represented the most severe manifestation along a spectrum of anomalies of the tendon in patients with congenital superior oblique palsy. Anatomic abnormalities, ranging from long, floppy tendons to missing tendons, may be the cause of the bilateral congenital superior oblique palsies with variable severity shown by other members of this family. With involvement of three successive generations, including the presence of male-to-male transmission, the pedigree demonstrates the autosomal-dominant pattern of inheritance of congenital superior oblique palsy. There appears to be high penetrance of the causative genetic mutation, because approximately 50% of offspring of the last two generations of the pedigree express the trait (Fig

Botelho and Giangiacomo . Congenital Superior Oblique 1). Sevel's17 study of the development of the extraocular muscles showed that mesenchymal tissue of the superomedial aspect of the orbit gives rise to the superior oblique tendon and the trochlea. Moreover, the extraocular muscle belly, origin, and insertion were found to develop simultaneously. The genetic defect responsible for the superior oblique palsy may code for an unidentified structural protein involved in the induction or the development of this mesenchymal tissue into the superior oblique tendon. The majority of prior case reports of familial congenital superior oblique palsy also support the autosomaldominant inheritance of the trait. 5-7 All prior case reports had involvement of two family members by examination. These reports did not definitively demonstrate the genetic transmission of congenital superior oblique palsy, however. Unlike this pedigree, all affected family members of previous reports had unilateral involvement. The cause of the congenital superior oblique palsy and the status of the superior oblique tendon were not known in any patients of previous familial reports. Visual sensory testing of prior case reports showed normal stereo acuity and fusion in most patients. 6 The affected family members of this report, however, all had reduced stereo acuity, with suppression noted in two members. The etiology of the congenital superior oblique palsy of prior familial case reports may have been the same or a new genetic mutation with resultant anatomic defects oflesser severity. Alternatively, these pedigrees may represent coincidental familial occurrence of sporadic cases or the genetic transmission of the trait by another mechanism, perhaps neurologic. The superior oblique traction test performed at the time of surgery can assist in detecting a markedly lax or absent superior oblique tendon. 18,19 In patients with superior oblique palsy, the traction test may direct surgery to the superior oblique tendon and help avoid the development of iatrogenic Brown syndrome. 1O,18 Superior oblique strengthening procedures, such as a tuck or resection of the tendon, have provided excellent results in patients with marked laxity of the tendon. 20 Absence of the superior oblique tendon precludes tucking and may necessitate other management options, such as extirpation of the inferior oblique, weakening of the contralateral yoke muscle, or the transposition of the vertical recti. 21 In conclusion, this family shows the autosomal-dominant inheritance of congenital superior oblique palsy. The occurrence of genetic transmission and the presence of anatomic anomalies of the superior oblique tendon should be considered in patients with congenital superior oblique palsy.

References 1. Ellis FD, Helveston EM, Superior oblique palsy: diagnosis and classification. Int Ophthalmol Clin 1976; 16(3): 12735.

2. Harley RD. Paralytic strabismus in children. Etiologic incidence and management of the third, fourth, and sixth nerve palsies. Ophthalmology 1980;87:24-43. 3. von Noorden GK, Murray E, Wong SY. Superior oblique paralysis. A review of 270 cases. Arch Ophthalmol 1986; 104: 1771-6. 4. Younge BR, Sutula F. Analysis of trochlear nerve palsies. Diagnosis, etiology, and treatment. Mayo Clin Proc 1977; 52:11-8. 5. Harris DJ Jr, Memmen JE, Katz NNK, Parks MM. Familial congenital superior oblique palsy. Ophthalmology 1986; 93:88-90. 6. Astle WF, Rosenbaum AL. Familial congenital fourth cranial nerve palsy. Arch Ophthalmol 1985; 103:532-5. 7. Franceschetti A. Uber doppelseitige, kongenitale (familiare) Trochlearislahmung und ihre Beziehung zur altemierenden Hyperphorie. Z Augenheilkd 1926; 59: 17 - 34. 8. Mansour AM, Reinecke RD. Central trochlear palsy. Surv Ophthalmol 1986;30:279-97 9. Duke-Elder S. System of Ophthalmology: VI. Ocular Motility and Strabismus. St Louis, CV Mosby Co, 1973;70030. 10. Helveston EM, Krach D, Plager DA, Ellis FD. A new classification of superior oblique palsy based on congenital variations in the tendon. Ophthalmology 1992;99:160915. 11. Helveston EM, Giangiacomo JG, Ellis FD. Congenital absence of the superior oblique tendon. Trans Am Ophthalmol Soc 1981;79:123-35. 12. Diamond GR, Katowitz JA, Whitaker LA et al. Variations in extraocular muscle number and structure in craniofacial dysostosis. Am J Ophthalmol 1980;90:416-8. 13. Lo CY, Nakamura K. Congenital absence of the superior oblique in Down's syndrome. Jpn Rev Clin Ophthalmol 1987;81:1312. 14. Pratt-Johnson JA. The development of vision, fusion and stereopsis. In: Pratt-Johnson JA, Tillson G, eds. Management of Strabismus and Amblyopia: A Practical Guide. New York: Thieme Medical Publishers, Inc, 1994; 1-6. 15. Hermann JS. Masked bilateral superior oblique paresis. J Pediatr Ophthalmol Strabismus 1981; 18:43-8. 16. Matsuo T, Ohtsuki H, Sogabe Y, et al. Vertical abnormal retinal correspondence in three patients with congenital absence of the superior oblique muscle. Am J Ophthalmol 1988; 106:341-5. 17. Sevel D. A reappraisal of the origin of human extraocular muscles. Ophthalmology 1981;88:1330-8. 18. Plager DA. Traction testing in superior oblique palsy. J Pediatr Ophthalmol Strabismus 1990;27:136-40. 19. Guyton DL. Exaggerated traction test for the oblique muscles. Ophthalmology 1981;88:1035-40. 20. Helveston EM. A new classification of superior oblique palsy. In: Kaufmann H, ed. Trans European Strabismological Assoc. Krakow, Poland, 1989;25-31. 21. Wallace DK, von Noorden GK. Clinical characteristics and surgical management of congenital absence of the superior oblique tendon. Am J Ophthalmol 1994; 118:63-9.

1511