Duane retraction syndrome is characterized by globe retraction and palpebral fissure narrowing on adduction, with restriction of abduction, adduction, or both. Usher syndrome type 2 consists of congenital bilateral sensorineural hearing loss that is mild to moderate in low frequencies and severe to profound in higher frequencies, intact vestibular responses, and retinitis pigmentosa. Retinitis pigmentosa is progressive, bilateral, symmetric retinal degeneration that begins with night blindness and constricted visual fields and eventually includes decreased central visual acuity.
Duane retraction syndrome has earlier been reported with various conditions such as retinitis pigmentosa, Bardet Biedl syndrome with atypical retinitis pigmentosa, pseudoretinitis pigmentosa, oculocutaneous albinism, cone rod dystrophy, and optic nerve hypoplasia. The case reported here is the first to depict a rare association between Duane retraction syndrome and Usher syndrome type 2.
A 21-year-old man presented to us with a history of inward deviation of the left eye noticed by his parents since birth, along with inability to move the same eye outward beyond midline. He gave a history of progressive difficulty in seeing clearly at night. Further, he had a history of deafness noticed by his parents since birth. He was the first born child of a non-consanguineous marriage. He was delivered spontaneously and at term after an uneventful antenatal period. There was no history of previous ocular surgery or trauma. Ophthalmological examination of family members was within normal limits.
Ocular examination revealed best-corrected visual acuity of 20/20 in both eyes, with no significant refractive error and near vision of N6 in both eyes. Slit-lamp evaluation of the anterior segment was normal. He had an anomalous head posture in the form of a compensatory face turn toward the left. Orthoptic examination revealed left esotropia of 30 prism diopters. Alternate cover test showed alternate esotropia. Secondary deviation was greater than primary deviation. Ocular motility examination revealed complete limitation of abduction of the left eye. On adduction of the left eye, there was narrowing of the palpebral fissure and globe retraction. These findings were suggestive of left Duane retraction syndrome type 1 (as per Huber’s classification) (Figure 1). There was no binocularity on Worth 4-dot test and absence of gross stereopsis on Titmus fly test.
Left esotropia with complete lack of abduction in the left eye, palpebral fissure narrowing, and globe retraction on adduction suggestive of type 1 Duane retraction syndrome.
Indirect ophthalmoscopy revealed bilateral attenuation of retinal vessels, waxy pallor of the optic nerve head, and perivascular clumps of pigment deposition in the mid peripheral retina. The pigmentation displayed a characteristic “bone spicule appearance” suggestive of typical retinitis pigmentosa (Figure 2).
Attenuation of retinal vessles, bone spicules in midperiphery, and waxy pallor of optic nerve head.
Full-field electroretinogram waveforms were extinguished for both rods and cones and were suggestive of retinitis pigmentosa.
Otolaryngological opinion was sought in view of his complaint of impaired hearing since birth. Extensive audiovestibular examination was done. Pure tone audiometry showed moderate hearing loss for lower frequencies and profound hearing loss for higher frequencies with a typical sloping configuration, which is characteristic of Usher syndrome type 2 (Figure 3). The patient was also noted to have a mild to moderate speech impediment, which is consistent with the congenital nature of the hearing loss. Vestibular function tests were within normal limits, which helped to further categorize the patient as a case of Usher syndrome type 2 because vestibular function is severely compromised in type 1 and moderately compromised in type 2 Usher syndrome.
Pure tone audiogram shows typical sloping configuration suggestive of Usher syndrome type 2.
Duane retraction syndrome is said to occur in 1% of patients with strabismus.1 The anatomic and histologic pathology lies in absent or partial development of the sixth nerve and nucleus. Branches from the third nerve are redirected to the lateral rectus muscle, which may exhibit a wide spectrum of mixed anomlous innervation from third nerve and (sub) normal sixth nerve innervation. The fact that literature points to Duane retraction syndrome as having frequently associated congenital malformations may link the disorder to an event at a critical point in embryogenic development (ie, the 4th to 10th week of gestation).2 Approximately 10% to 20% of patients with Duane retraction syndrome are known to be associated with congenital ocular and systemic conditions.3
Usher syndrome is a group of autosomal recessive disorders characterized by retinitis pigmentosa, bilateral congenital sensorineural hearing loss, and, in some cases, vestibular dysfunction. The prevalence of Usher syndrome is 3.0 to 6.2 per 100,000 population. Usher syndrome has been subcategorized into three distinct clinical types based on audiovestibular examination and has been linked to 10 distinct chromosomal regions. To date, eight different Usher syndrome genes have been identified.4 Usher syndrome type 1 is characterized by profound congenital deafness, retinitis pigmentosa, and bilateral vestibular areflexia. Patients with Usher syndrome type 2 display congenital moderate to severe hearing loss, retinitis pigmentosa, and normal vestibular function. Usher syndrome type 3 is characterized by progressive hearing loss, retinitis pigmentosa, and progressive vestibular deficiency.
Accurate diagnosis of Usher syndrome requires careful genetic, ophthalmological, and audiovestibular diagnostic procedures. Molecular genetics studies have shown the existence of USH1 and USH2 proteins, which are integrated in a protein network known as Usher interactome. Many of the USH proteins also interact with other proteins present in the inner ear and retina. These additional interacting proteins may cause Usher syndrome, hearing loss, or retinal dystrophies. The localization of the Usher proteins in the hair cells of the organ of Corti and in the photoreceptor cells suggests that they play an important role in the neurosensory function of both the inner ear and the retina.
As far as rehabilitation of retinitis pigmentosa seen in patients with Usher syndrome is concerned, recent advances have been made in the field of gene therapy wherein the specific genes involved are targeted. Slowing or stopping photoreceptor degeneration or apoptosis by development and application of growth factors or calcium blocker applications, vitamin supplementation, and endogenous cone viability factors has been attempted. In addition, replacement of lost cells by transplantation and use of stem or precursor cells has also been tried.5 Recent creation of a specific microchip for this disease has been a revolutionary development because it permits the identification of mutations in 30% to 50% of the affected patients and requires only a small DNA sample.
This case highlights the importance of a meticulous history and examination in cases of Duane retraction syndrome, including detailed fundus examination by indirect ophthalmoscopy. Presence of retinitis pigmentosa in such cases should prompt the ophthalmologist to inquire about hearing impairment and warrants a complete otolaryngological examination including pure tone audiometry. Prompt diagnosis is of public health importance because it can provide opportunity for genetic counselling and family planning for the affected person, improve habilitation potentials by choosing optimal communication strategies, and facilitate education and career decisions for those diagnosed as having Usher syndrome. Importantly, it can also help to provide a cohort for the development of treatment protocols for Usher syndrome.
Guirgis et al. reported a case of Duane retraction syndrome with cone rod dystrophy.6 McCullah and Cummings described a patient with unilateral Duane retraction syndrome and pseudo retinitis pigmentosa.7 Pelit et al. reported a case of a middle-aged woman with Duane retraction syndrome type 1 associated with retinitis pigmentosa.8 Unlike our patient, she did not complain of hearing loss, which rules out the possibility of Usher syndrome. To our knowledge, the patient described here is the first reported case of Duane retraction syndrome accompanying Usher syndrome type 2.
- Gurwood AS, Terrigno CA. Duane’s retraction syndrome: literature review. Optometry. 2000;71:722–726.
- Blodi FC, van Allen MW, Yarbrough JC. Duane’s syndrome: a brain stem lesion: an electromyographic study. Arch Ophthalmol. 1964;72:171–177. doi:10.1001/archopht.1964.00970020171007 [CrossRef]
- Pfaffenbach DD, Cross HE, Kearns TP. Congenital anomalies in Duane’s retraction syndrome. Arch Ophthalmol. 1972;88:635–639. doi:10.1001/archopht.1972.01000030637013 [CrossRef]
- Moller CG, Kimberling WJ, Davenport SL, et al. Usher syndrome: an otoneurologic study. Laryngoscope. 1989;99:73–79.
- Ayuso C, Millan JM. Retinitis pigmentosa and allied conditions today: a paradigm of translational research. Genome Medicine. 2010;2:34. doi:10.1186/gm155 [CrossRef]
- Guirgis MF, Thornton SS, Tychsen L, Lueder GT. Cone rod retinal dystrophy and Duane retraction syndrome in a patient with achondroplasia. J AAPOS. 2002;6:400–401. doi:10.1067/mpa.2002.129561 [CrossRef]
- McCullah D, Cumnings RW. Pseudoretinitis pigmentosa. Am J Optom Physiot Opt. 1987;61:56–60. doi:10.1097/00006324-198401000-00011 [CrossRef]
- Pelit A, Aydogan N, Oto S, Haciyakupoglu G, Yilmaz Z, Akova YA. Duane’s retraction syndrome in association with retinitis pigmentosa. J AAPOS. 2003;7:423–424. doi:10.1016/S1091-8531(03)00215-5 [CrossRef]