Ocular Characteristics and Genotype-Oriented Disease Spectrum of Alström Syndrome in Taiwan.

Purpose: This study aimed to describe the ophthalmological features of Alström syndrome, a rare syndromic ciliopathy, and to delineate the genotype-associated disease spectrum.

Methods: Eight Taiwanese patients were recruited for this study. Pathogenic variants were identified using next-generation sequencing, and medical records were reviewed for systemic involvement. Best-corrected visual acuity, cycloplegic refraction, blue light fundus autofluorescence imaging, International Society for Clinical Electrophysiology of Vision-standard full-field flash electroretinography, optical coherence tomography, and visual field testing were obtained and studied retrospectively.

Results: Common ocular manifestations included hyperopia, nystagmus, photophobia, and visual impairment. Most patients also exhibited obesity, sensorineural hearing loss, and developmental delays. Phenotype variability was observed in age of onset (0-8 years), severity of visual impairment, and extent of extraocular involvement. Electroretinography results reflected varying degrees of retinal degeneration. We identified c.11110_11128del as a genotype frequently occurring in Asian populations that demonstrated a more severe phenotype within our cohort. In addition, we discovered three novel variants, including a LINE-1 insertion in exon 8 (c.3565insL1), c.6166_6167insAT, and 8077del.

Conclusions: Alström syndrome may manifest with early-onset ocular and syndromic features, or demonstrate a later onset with limited extraocular involvement. This is the first report of a LINE-1 insertion in ALMS1, with affected patients exhibiting comparatively mild phenotypes.

Translational Relevance: Combined ophthalmological and extraocular phenotypes combined may aid in diagnosing this rare disease and differentiating it from other possible causes.