UNDERSTANDING PRADER-WILLI SYNDROME: FROM MOLECULAR DIAGNOSIS TO THERAPEUTIC INNOVATIONS
Abstract
Prader-Willi syndrome (PWS) is a rare, multisystem genetic disorder with an epigenetic basis, caused by a lack of paternal gene expression in the region of chromosome 15q11-q13. Key clinical manifestations include severe hypotonia early in life, hyperphagia leading to obesity, short stature, hypogonadism, cognitive impairment, and multiple endocrine disorders such as growth hormone deficiency, hypothyroidism, and central adrenal insufficiency. Hypothalamic dysfunction plays a central role in the pathogenesis of PWS, responsible for many somatic and behavioral symptoms, including disorders of satiety, temperature regulation, sleep, and emotion. Obesity and its complications - including type 2 diabetes and cardiovascular disease - are a major cause of morbidity and mortality in this group of patients. Molecular diagnosis is mainly based on DNA methylation analysis, which allows detection of all types of genetic alterations in PWS. Currently, there is no causal treatment for the syndrome, and effective management requires a multidisciplinary approach including hormonal treatment, strict dietary control, behavioral interventions, rehabilitation, and possibly pharmacotherapy and new therapeutic options such as GLP-1 agonists, topiramate, oxytocin, naltrexone-bupropion, and matfromin.
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