Abstract
Werner Syndrome (WS) is a rare autosomal recessive disorder characterized by accelerated aging and a broad spectrum of clinical manifestations. This case report presents a unique instance of WS from Pakistan, featuring a novel mutation in the WRN gene. Known as progeria adultorum, WS typically manifests post-pubertally due to mutations in the WRN gene, which plays a key role in DNA repair and genomic maintenance.
A 28-year-old woman presented with non-healing bilateral leg ulcers, dry skin, and photopsia. She exhibited multiple signs of premature aging, including short stature, early hair graying, and bilateral cataracts. Her medical history included hypothyroidism, cataract surgery, and recurrent gastrointestinal infections. Genetic testing confirmed a homozygous pathogenic variant in the WRN gene, thereby establishing the diagnosis of WS.
This case highlights the diagnostic challenges associated with rare genetic syndromes. The patient's diverse clinical signs—such as persistent ulcers, cataracts, and failure to experience a pubertal growth spurt—were consistent with diagnostic criteria for WS. The report explores the pathophysiology of WS, particularly the role of WRN mutations in impaired DNA repair and increased genomic instability, which significantly elevates cancer risk.
There is currently no specific treatment for WS; management remains supportive, focusing mainly on symptomatic relief. This case emphasizes the importance of early recognition, targeted genetic testing, and multidisciplinary care. Greater awareness and understanding of WS are essential for timely diagnosis and intervention. Furthermore, ongoing genetic research may offer valuable insights into disease mechanisms and potential therapeutic strategies, ultimately aiming to improve patient outcomes.
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