Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2

Prader-Willi syndrome due to paternal deletion of 15q11-q13 type 2 (PWS type 2 deletion) is a specific genetic subtype of Prader-Willi syndrome (PWS) caused by a larger deletion on the paternally inherited chromosome 15, spanning from breakpoint BP1 to breakpoint BP3 in the 15q11.2-q13 region. This type 2 deletion (also called class I deletion) encompasses approximately 6 Mb and includes four additional genes (NIPA1, NIPA2, CYFIP1, and TUBGCP5) located between BP1 and BP2 that are not deleted in the smaller type 1 (class II) deletion. PWS is an imprinted disorder, meaning only the paternal copy of genes in this region is active; loss of these paternally expressed genes leads to the characteristic clinical features. The syndrome affects multiple body systems. In the neonatal period, affected infants typically present with severe hypotonia (low muscle tone), feeding difficulties, and failure to thrive. During early childhood, an insatiable appetite (hyperphagia) develops, which, if unmanaged, leads to severe obesity. Other key features include short stature, hypogonadism with incomplete pubertal development, intellectual disability (usually mild to moderate), behavioral problems such as temper tantrums and obsessive-compulsive tendencies, and characteristic facial features including a narrow forehead, almond-shaped eyes, and a thin upper lip. Some studies suggest that individuals with the larger type 2 deletion may have slightly more pronounced cognitive and behavioral difficulties compared to those with the smaller type 1 deletion, though clinical overlap is substantial. There is no cure for Prader-Willi syndrome, but management is multidisciplinary. Growth hormone therapy is a standard treatment that improves height, body composition, and muscle tone. Strict dietary supervision and caloric restriction are essential to prevent life-threatening obesity. Behavioral interventions, speech therapy, physical therapy, and educational support are important components of care. Sex hormone replacement may be considered for hypogonadism. Early diagnosis and intervention significantly improve outcomes and quality of life.

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