Alagille syndrome is an uncommon autosomal dominant disorder associated with mutations in the genes coding for the Notch signaling pathway ligand Jagged 1 (JAG1) and the Notch2 receptor (NOTCH2).1,2 The syndrome manifests clinically as intrahepatic bile duct hypoplasia, skeletal abnormalities, cardiovascular defects, and a characteristic facial appearance.3 Individuals with Alagille syndrome have various ocular abnormalities, including posterior embryotoxon, optic disc anomalies, diffuse fundus hypopigmentation, abnormalities of the iris, speckling of the retinal pigment epithelium, and strabismus.4 To our knowledge, there has been no report of asymmetric lateral rectus muscle insertion with recurrent esotropia in a patient with Alagille syndrome.
We describe a patient with Alagille syndrome concurrent with asymmetric lateral rectus muscle insertion who developed recurrent esotropia 1 month after strabismus surgery.
A 2-year-old boy with Alagille syndrome was referred to the Department of Pediatric Ophthalmology of Keimyung University's Dongsan Medical Center for evaluation of esotropia predominantly observed in the right eye. We could not determine the patient's visual acuity due to his developmental delay. Manifest refraction was +1.00 +0.50 × 90° in both eyes. Examination of the patient's anterior segment revealed no posterior embryotoxon or abnormalities of the iris, and a dilated fundus examination revealed no anomalies of the optic disc or fundus. The patient's fixation and smooth pursuit were intact, and movement in both eyes was normal. The deviation angle in the primary position was measured with the prism cover test and was found to be 35 prism diopters (PD) of esotropia for both distance and near.
In May 2016, we performed a bilateral medial rectus muscle recession. The angle of esodeviation was maintained within 10 PD for both distance and near until 1 month postoperatively. Thereafter, the angle of esodeviation gradually increased, reaching 30 PD of esotropia for both distance and near in May 2018. Given the dominance of the left eye, we decided to perform unilateral lateral rectus muscle resection in the right eye.
After inferotemporal conjunctival fornix incisions were made during surgery, we found that the lateral rectus muscle was absent anterior to the equator of the right eye (Figure 1). Notably, we assumed that the patient had congenital unilateral aplasia of the right lateral rectus muscle; thus, we performed left lateral rectus muscle resection. Fortunately, the left lateral rectus muscle was easily detected and we could perform the operation successfully. Unexpectedly, postoperative magnetic resonance imaging revealed a right lateral rectus muscle that inserted considerably posterior to the equator in the right eye (Figure 2), such that we could not locate the insertion of his right lateral rectus muscle intraoperatively.
An intraoperative photograph demonstrating the absence of the lateral rectus muscle anterior to the equator in the right eye.
Postoperative magnetic resonance image showing that the right lateral rectus muscle was inserted considerably posterior to the equator, whereas the left lateral rectus muscle was inserted anterior to the equator. The two white arrows indicate the insertion sites of the lateral rectus muscles.
This is the first case report of asymmetric lateral rectus muscle insertion with recurrent esotropia in a patient with Alagille syndrome. In the largest case series of Alagille syndrome,4 the frequency of strabismus (5%) was low compared with more common findings (eg, posterior embryotoxon [95%]). Although Puklin et al.5 reported that two of the five patients with Alagille syndrome in their case series had esotropia, they did not mention asymmetric lateral rectus muscle insertion. Few studies6,7 have reported an asymmetric insertional shape of the rectus muscle in patients without Alagille syndrome. The case presented here is unique due to the significant difference in the distance from the corneoscleral limbus to the lateral rectus muscle insertion between the right and left eyes. Given that the prevalence rates of asymmetric lateral rectus muscle insertion and Alagille syndrome are low, it might be expected that the number of patients with both abnormalities would be extremely low. We cannot be certain whether the presence of these two conditions in this patient was a coincidental finding or whether asymmetric lateral rectus muscle insertion is an abnormality associated with Alagille syndrome. Further cases are needed to clarify this issue.
Alagille syndrome has characteristics of autosomal dominant inheritance with variable expression and reduced penetrance, and mutations in the JAG1 gene have been recognized.8 The JAG1 gene encodes a ligand for Notch-related receptors.9 The Notch/Jagged signaling pathway is essential for cellular differentiation/proliferation and may contribute to ocular development. Asymmetric lateral rectus muscle insertion might constitute a portion of the abnormal ocular development caused by the JAG1 gene mutation.
Due to the rarity of Alagille syndrome, meticulous preoperative imaging work-up, including magnetic resonance imaging, is indispensable for patients with Alagille syndrome who have strabismus. It is especially important for those who must undergo surgery to facilitate early detection of a possible abnormal extraocular muscle insertion.
- Warthen DM, Moore EC, Kamath BM, et al. Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat. 2006;27:436–443. doi:10.1002/humu.20310 [CrossRef]
- McDaniell R, Warthen DM, Sanchez-Lara PA, et al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet. 2006;79:169–173. doi:10.1086/505332 [CrossRef]
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- Puklin JE, Riely CA, Simon RM, Cotlier E. Anterior segment and retinal pigmentary abnormalities in arteriohepatic dysplasia. Ophthalmology. 1981;88:337–347. doi:10.1016/S0161-6420(81)35026-X [CrossRef]
- Kushner BJ, Morton GV. A randomized comparison of surgical procedures for infantile esotropia. Am J Ophthalmol. 1984;98:50–61. doi:10.1016/0002-9394(84)90188-0 [CrossRef]
- Cho HK, Shin SY. Is the insertional anatomy of rectus extraocular muscles binocularly symmetrical?Ophthalmic Res. 2010;43:179–184. doi:10.1159/000272021 [CrossRef]
- Li L, Krantz ID, Deng Y, et al. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet. 1997;16:243–251. doi:10.1038/ng0797-243 [CrossRef]
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