Ho-ho-ho! Gather ’round, my little elves, for a tale of scientific wonder, not from the North Pole, but from the realm of medicine, where the mysteries of acquired early-onset bilateral cataracts in youngsters are being unwrapped like presents on Christmas morn!

In a workshop not of toys, but of high-tech sequencing gadgets, a group of merry researchers embarked on an observational study, much like I check my list twice, to analyze the genetic secrets of individuals from 18 months to a sprightly 35 years with these frosty eye lenses.

With a sleigh full of 347 patients, 313 of whom were as young as the children eagerly awaiting my visit on Christmas Eve, the scientists used a magical next-generation sequencing panel of 66 genes to seek out the mischievous genetic variants causing this visual blizzard.

And what did they find in their stocking? A total of 74 pathogenic or likely pathogenic variants in 69 patients, much like finding a variety of cookies left for me under the tree. Among these, 64 were single nucleotide variants (SNVs) dancing on 24 genes, and 10 were copy number variants (CNVs) of varying sizes, prancing across the genomic landscape.

The crystallin genes, much like the star atop the Christmas tree, shone the brightest, accounting for 27.0% of all variants. Some variants were as recurrent as the classic carols we sing each year, with CRYBA1 c.215+1G>A appearing thrice, and others like CRYBA1 c.272_274delGAG, CRYBB2 c.463C>T and c.562C>T, and CRYAA c.62G>A each making a double appearance.

In a twist as surprising as a reindeer with a red nose, CNV deletions associated with 1q21.1 microdeletion syndrome were found in five patients, their sizes ranging from 1.32-2.41 Mb, like varying sizes of snowflakes.

And in a heartwarming turn of events, akin to discovering a long-lost toy-making manual, biallelic variants in CYP27A1 led to the diagnosis of cerebrotendinous xanthomatosis in two siblings, a rare but treatable condition often heralded by these cataracts.

This study, my dear friends, is like a beacon in the wintry night, showing the utility of genetic testing in clarifying the cause of these cataracts. It’s a gift that keeps on giving, informing patient management and offering genetic counseling to families, ensuring that the risk of recurrence is known, much like I keep track of who’s naughty or nice.

So let’s jingle our bells for science, for it brings tidings of comfort and joy to those with acquired early-onset bilateral cataracts, lighting the way like Rudolph’s red nose on a foggy Christmas Eve! 🎅🔬👀