Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is a complex genetic disorder caused by lack of expression of  genes on chromosome 15q11.2-q13. It presents with severe hypotonia and feeding difficulties in infancy, followed by hyperphagia and obesity in early childhood. Individuals typically show cognitive impairment, short stature, hypogonadism, and behavioral issues. The diagnosis is confirmed by DNA methylation testing, which detects abnormal imprinting or deletions. Early diagnosis and multidisciplinary care can improve outcomes and quality of life.

1. Neonatal Period

• Decreased fetal movement and low birth weight.
• Hypotonia, weak cry, poor sucking, excessive sleepiness.
• Small hands and feet (acromicria).
• Characteristic facial features: narrow forehead, almond-shaped eyes, downturned mouth, thin upper lip, small jaw.
• Delayed motor milestones and abnormal genitalia (cryptorchidism in males, hypoplastic labia in females).

2. Infantile Period

• Persistent hypotonia and feeding difficulties leading to poor weight gain.
• Gradual improvement in muscle tone by 12 months.
• Delayed developmental milestones, especially in speech due to oromotor dysfunction.

3. Childhood

• Onset of hyperphagia around age 2–3, often with food-seeking, hoarding, and pica.
• Behavioral issues: temper tantrums, skin picking, aggression, and compulsive behaviors.
• Intellectual disability common (IQ 20–105), with relative strengths in verbal comprehension but weaknesses in attention and abstract thinking.

4. Adulthood

• Ongoing obesity-related complications (e.g., sleep apnea).
• Continued behavioral and cognitive challenges.
• Hypothalamic dysfunction leads to osteoporosis, hypogonadism, delayed or absent puberty, and infertility.
• Short stature due to lack of pubertal growth spurt and delayed bone maturation.

PWS is a genetic disorder caused by the absence or dysfunction of genes in the 15q11–q13 region of chromosome 15.

1. Paternal deletion: ~70% of cases

• It is caused by a deletion of the paternal 15q11.2–q13 region.
• This is the most common subtype and shows typical clinical features of PWS.

2. Maternal uniparental disomy (UPD): ~25% of cases

• Both copies of chromosome 15 are inherited from the mother, with no paternal contribution.
• These individuals may have milder facial features, slightly better cognitive function, and a higher risk of autism spectrum traits.

3. Imprinting defect: 1–5% of cases

• The paternal chromosome is present but fails to express due to an imprinting error.
• This form is rare and may be familial, carrying a recurrence risk.                                                                                                             
• PWS typically occurs sporadically, and most cases are not inherited. However, advanced maternal age may be associated with a slightly increased risk of maternal UPD cases.