Alagille syndrome linked to glaucoma risk in study of 2 brothers
Findings suggest monitoring of these patients for the serious eye disease
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Two adult brothers with impaired vision due to glaucoma, a serious eye condition that may lead to irreversible vision loss, were found to have Alagille syndrome, a study showed.
These cases expand the spectrum of eye abnormalities that may occur in people with Alagille and suggest that clinicians should monitor these patients for glaucoma, researchers noted.
“Early detection and intervention are crucial for vision preservation, underscoring the clinical importance of proactive glaucoma screening in this population,” they wrote.
The study, “Ocular Findings in Siblings With Alagille Syndrome: A Report of Two Cases,” was published in Cureus.
Alagille syndrome mainly caused by mutations in copy of JAG1 gene
Alagille syndrome is mainly caused by mutations in one copy of the JAG1 gene, which is involved in embryonic development. The disease can lead to a wide range of symptoms, including liver, heart, and bone problems, as well as characteristic facial features and eye abnormalities.
Eye issues typically include posterior embryotoxon, a white ring that lines the transparent membrane covering the eyeballs, and optic disc anomalies. The optic disc is the circular spot at the back of the eye where the retina, the light-sensitive tissue lining the back of the eye, connects with the optic nerve, which relays signals between the eye and the brain.
In this study, researchers from the University of Puerto Rico reported the case of two Latino brothers with glaucoma that was likely caused by Alagille syndrome. Glaucoma is a group of conditions typically linked to elevated pressure inside the eyes, known as intraocular pressure, that damages the optic nerve and can lead to vision loss.
One of the brothers, a 32-year-old man with a history of mild cognitive impairment, hearing loss, and epilepsy, was referred to the researchers’ genetic clinic due to the detection of damage to the light-sensing cells in the retina on a previous eye exam.
The physical examination revealed certain facial features, including an abnormally small jaw, and the man reported experiencing difficulty seeing in low light or darkness since childhood. His medical history also included a shortage of tubes that transport the digestive fluid bile from the liver to the intestines — a hallmark of Alagille — as well as chronic cholestasis, or slowed bile flow, and heart problems.
Eye evaluation revealed moderate vision loss in the right eye and severe vision loss in the left eye, abnormal eye movements, posterior embryotoxon, high intraocular pressure, optic nerve abnormalities, and thinning of the nerve fiber layer in the retina.
This ultimately led to a diagnosis of glaucoma, which was initially treated with brimonidine, sold under the brand name Alphagan P, among others. This treatment was later switched to dorzolamide, another glaucoma medication, due to adverse reactions.
At the last follow-up, about one year later, his intraocular pressure had decreased, with no progression of vision loss. Genetic testing revealed the presence of a previously described JAG1 mutation, c.925G>C, whose disease-causing effects remain unclear.
JAG1 mutation also detected in men’s father
After the man’s Alagille diagnosis, his 38-year-old brother presented to the researchers’ clinic. He had developmental delay, undescended testicles, and iris coloboma — when part of the iris is missing — in both eyes.
He also showed some facial features, heart problems, and a history of seizures. Moreover, he had motor neuron disease, which is marked by progressive degeneration of the nerves that control voluntary movements.
Comprehensive eye evaluation detected vision problems in both eyes, increased intraocular pressure, and other eye alterations that also resulted in a glaucoma diagnosis. He was treated with brimonidine, which effectively reduced his intraocular pressure. His condition remained stable over the course of one year.
These cases broaden the recognized spectrum of [Alagille syndrome presentations] and underscore the importance of targeted glaucoma screening and longitudinal follow-up, particularly in underrepresented populations.
Genetic testing revealed the same mutation found in his brother, which was also detected in their father.
“Previous studies … have shown that most patients with the syndrome have good visual acuity despite structural ocular anomalies,” the researchers wrote. “In our case, both patients had significant visual impairment in both eyes,” which “may be due to glaucoma, leading to optic [nerve damage] and visual field loss.”
The team noted that observed eye abnormalities, including posterior embryotoxon and iris coloboma, may contribute to impaired drainage of the water-like fluid that fills the front part of the eye and increased intraocular pressure.
“These cases broaden the recognized spectrum of [Alagille syndrome presentations] and underscore the importance of targeted glaucoma screening and longitudinal follow-up, particularly in underrepresented populations,” the researchers wrote.
They noted, however, that larger studies are needed to confirm the connection between Alagille and glaucoma.
