<p class="first" id="d3941674e69">Prader-Willi syndrome is a rare genetic neurodevelopmental
disorder resulting from
the loss of expression of maternally imprinted genes located in the paternal chromosomal
region, 15q11-13. Impaired hypothalamic development and function is the cause of most
of the phenotypes comprising the developmental trajectory of Prader-Willi syndrome:
from anorexia at birth to excessive weight gain preceding hyperphagia, and early severe
obesity with hormonal deficiencies, behavioural problems, and dysautonomia. Growth
hormone deficiency, hypogonadism, hypothyroidism, premature adrenarche, corticotropin
deficiency, precocious puberty, and glucose metabolism disorders are the main endocrine
dysfunctions observed. Additionally, as a result of hypothalamic dysfunction, oxytocin
and ghrelin systems are impaired in most patients. Standard pituitary and gonadal
hormone replacement therapies are required. In this Review, we discuss Prader-Willi
syndrome as a model of hypothalamic dysfunction, and provide a comprehensive description
of the accumulated knowledge on genetics, pathophysiology, and treatment approaches
of this rare disorder.
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