暂无摘要。

UNASSIGNED: : Alagille syndrome (AS) is a multisystem disorder associated with a range of ocular anomalies affecting the anterior and posterior segments. While chorioretinal abnormalities have been reported in Alagille Syndrome, identification of macular dystrophy and detailed clinical and electrophysiologic descriptions are scarce.
UNASSIGNED: : A retrospective review was conducted to identify patients with a diagnosis of AS and retinal disease who were evaluated in the Division of Pediatric Ophthalmology, Strabismus, and Adult Motility at UPMC Children\'s Hospital of Pittsburgh. Criteria of AS included biopsy-proven bile duct hypoplasia, presence of major clinical features of AS, and molecular confirmation of the JAG1 gene.
UNASSIGNED: : This cohort included three patients, two females and one male, diagnosed with JAG1-Alagille syndrome. The diagnosis was made before 2 years of life in all patients. The mean follow-up period in our center was 8 years. All patients were found to have retinal pigmentary changes, macular atrophy, choroidal thinning, optic disc anomalies, and progressive decrease in vision. Marked retinal and macular dysfunction were found in electrophysiological studies.
UNASSIGNED: : Three patients with molecularly confirmed Alagille syndrome demonstrated unusual retinal and macular findings, with two showing progressive vision loss. Due to the rarity of retinal findings in AS and the observed progression of disease in our patients, clinical genetic testing for retinal dystrophies could be completed in two cases. These investigations failed to reveal a separate molecular cause for the observed retinal dystrophy, helping to confirm the association with JAG1-related AS.

Alagille syndrome is an autosomal dominant disorder usually caused by pathogenic variants of the JAG1 gene. In the past, cholestasis was a condition sine qua non for diagnosis of the syndrome. However, recent advancements in genetic testing have revealed that clinical presentations vary from lack of symptoms, to multiorgan involvement. Tetralogy of Fallot, the most frequent complex congenital heart defect in Alagille Syndrome, very rarely leads to renal failure requiring dialysis - there are only single reports of such cases in the literature, with none of them in Alagille Syndrome.
A 41-year-old woman suffering from cyanosis, dyspnea and plethora was admitted to the hospital. The patient suffered from chronic kidney disease and tetralogy of Fallot and had been treated palliatively with Blalock-Taussig shunts in the past; at admission, only minimal flow through the left shunt was preserved. These symptoms, together with impaired mental status and dysmorphic facial features, led to extensive clinical and genetic testing including whole exome sequencing. A previously unknown missense variant c.587G > A within the JAG1 gene was identified. As there were no signs of cholestasis, and subclinical liver involvement was only suggested by elevated alkaline phosphatase levels, the patient was diagnosed with incomplete Alagille Syndrome. End-stage renal disease required introduction of renal replacement therapy. Continuous ambulatory peritoneal dialysis was chosen and the patient\'s quality of life significantly increased. However, after refusal of further treatment, the patient died at the age of 45.
Tetralogy of Fallot should always urge clinicians to evaluate for Alagille Syndrome and offer patients early nephrological care. Although tetralogy of Fallot rarely leads to end-stage renal disease requiring dialysis, if treated palliatively and combined with renal dysplasia (typical of Alagille Syndrome), it can result in severe renal failure as in the presented case. There is no standard treatment for such cases, but based on our experience, peritoneal dialysis is worth consideration. Finally, clinical criteria for the diagnosis of Alagille Syndrome require revision. Previously, diagnosis was based on cholestasis - however, cardiovascular anomalies are found to be more prevalent. Furthermore, the criteria do not include renal impairment, which is also common.