Derek K Ho1, Alex V Levin2, William V Anninger3, David A Piccoli3, Ralph C Eagle2. 1. Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pa., USA. 2. Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pa., USA; Wills Eye Hospital, Philadelphia, Pa., USA. 3. Children's Hospital of Philadelphia, Philadelphia, Pa., USA.
Abstract
BACKGROUND: Alagille syndrome is an autosomal dominant disorder characterized by neonatal cholestasis, characteristic facies, and cardiac abnormalities. Ocular abnormalities include posterior embryotoxon, mosaic pattern of iris stromal hypoplasia, microcornea, optic disc drusen, and pigmentary retinopathy. We present the second report of ocular pathology in two cases of Alagille syndrome. METHODS: Gross and histologic preparations of four eyes of two patients. RESULTS: Posterior embryotoxon is seen in both cases, with iris processes extending to the embryotoxon in case 1. Case 1 exhibited distinctly abnormal iris stroma with a prominent cleft separating the anterior and posterior stroma. Lacy vacuolization of the iris pigment epithelium was seen in case 2. CONCLUSIONS: Alagille syndrome is primarily a hepatic disorder but presents with several distinct ocular pathologic features, most specifically posterior embryotoxon. This and the unusual iris stroma may be caused by improper migration of neural crest cells due to mutation in the Jagged 1 gene that causes Alagille syndrome. Patients with Alagille syndrome rarely present to ocular autopsy. Pathology findings may help us better understand the pathophysiology of the ocular abnormalities in this disorder.
BACKGROUND:Alagille syndrome is an autosomal dominant disorder characterized by neonatal cholestasis, characteristic facies, and cardiac abnormalities. Ocular abnormalities include posterior embryotoxon, mosaic pattern of iris stromal hypoplasia, microcornea, optic disc drusen, and pigmentary retinopathy. We present the second report of ocular pathology in two cases of Alagille syndrome. METHODS: Gross and histologic preparations of four eyes of two patients. RESULTS: Posterior embryotoxon is seen in both cases, with iris processes extending to the embryotoxon in case 1. Case 1 exhibited distinctly abnormal iris stroma with a prominent cleft separating the anterior and posterior stroma. Lacy vacuolization of the iris pigment epithelium was seen in case 2. CONCLUSIONS:Alagille syndrome is primarily a hepatic disorder but presents with several distinct ocular pathologic features, most specifically posterior embryotoxon. This and the unusual iris stroma may be caused by improper migration of neural crest cells due to mutation in the Jagged 1 gene that causes Alagille syndrome. Patients with Alagille syndrome rarely present to ocular autopsy. Pathology findings may help us better understand the pathophysiology of the ocular abnormalities in this disorder.
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