Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1

Prader-Willi syndrome due to paternal deletion of 15q11-q13 type 1 (PWS del type 1) is a specific genetic subtype of Prader-Willi syndrome caused by a larger class of deletion on the paternally inherited chromosome 15. In this subtype, the deletion extends from breakpoint 1 (BP1) to breakpoint 3 (BP3), encompassing approximately 6 Mb of genomic material in the 15q11.2-q13 region. This is in contrast to the type 2 deletion, which spans from BP2 to BP3 and is slightly smaller. Because the genes in this region are subject to genomic imprinting and are normally expressed only from the paternal allele, loss of the paternal copy results in absence of critical gene products, including SNRPN, MAGEL2, NDN, and the SNORD116 snoRNA cluster, among others. The type 1 deletion additionally removes four non-imprinted genes between BP1 and BP2 (NIPA1, NIPA2, CYFIP1, and TUBGCP5), which may contribute to a somewhat more severe neurobehavioral phenotype compared to type 2 deletions. Clinically, affected individuals present in the neonatal period with severe hypotonia, feeding difficulties, and failure to thrive. During early childhood, the phenotype shifts to include hyperphagia (an insatiable appetite) and progressive obesity if caloric intake is not strictly managed. Other key features include short stature due to growth hormone deficiency, hypogonadism, intellectual disability (typically 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. Multiple body systems are affected, including the endocrine, neurological, musculoskeletal, and reproductive systems. Treatment is multidisciplinary and symptomatic. Growth hormone therapy is a cornerstone of management, improving height, body composition, and muscle tone. Strict dietary supervision is 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. There is currently no cure, but early diagnosis and comprehensive management significantly improve quality of life and outcomes.

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