Prader Willi Syndrome Flashcards
A 3-year-old boy is brought to the pediatrician due to concerns about his eating habits and weight gain. The child had significant hypotonia at birth and required feeding assistance during infancy. Over the past year, his parents report an insatiable appetite and increasing difficulty in managing his food intake, resulting in significant weight gain. On examination, he has short stature, hypogonadism, and almond-shaped eyes. Genetic testing is ordered. Which of the following is the most likely underlying genetic abnormality?
a. Trinucleotide repeat expansion in the FMR1 gene
b. Segmental deletion of the paternal allele on chromosome 15q11-q13
c. Segmental deletion of the maternal allele on chromosome 15q11-q13
d. Uniparental disomy with two paternal copies of chromosome 15
e. Mutation in the UBE3A gene
Answer:
b. Segmental deletion of the paternal allele on chromosome 15q11-q13
Explanation:
This child’s presentation of early hypotonia, feeding difficulties during infancy, followed by hyperphagia, obesity, hypotonia, short stature, hypogonadism, and characteristic facial features such as almond-shaped eyes is classic for Prader-Willi Syndrome (PWS). Hypotonia at birth is often the first sign of the condition. PWS is caused by the lack of expression of paternally inherited genes on chromosome 15q11-q13, which may result from a paternal deletion, maternal uniparental disomy (two maternal copies of chromosome 15), or an imprinting defect. In contrast, a maternal deletion or paternal uniparental disomy would cause Angelman Syndrome, which presents with a very different clinical picture.
What is the genetic mechanism behind Prader-Willi Syndrome?
Lack of expression of paternally inherited genes on chromosome 15q11-q13, typically due to a paternal deletion or maternal uniparental disomy.
What is often the first sign of Prader-Willi Syndrome on delivery?
Significant hypotonia during infancy.
What are the key neonatal features of Prader-Willi Syndrome?
Severe hypotonia, poor feeding, and failure to thrive.
What is the hallmark childhood feature of Prader-Willi Syndrome?
Hyperphagia (insatiable appetite) leading to obesity.
What are common physical findings in Prader-Willi Syndrome?
Almond-shaped eyes, small hands and feet, hypogonadism, and short stature.
What are the common behavioral features of Prader-Willi Syndrome?
Temper tantrums, stubbornness, compulsive behaviors, and cognitive delays.
What is the first-line treatment for Prader-Willi Syndrome?
Caloric restriction to prevent obesity.
Growth hormone (GH) therapy to improve growth and body composition.
How can Prader-Willi Syndrome be confirmed diagnostically?
Methylation analysis to detect the absence of the paternal allele at 15q11-q13.
What is the prognosis for individuals with Prader-Willi Syndrome?
The prognosis of Prader-Willi Syndrome varies.
With early diagnosis and intervention, individuals can achieve a better quality of life.
Growth hormone therapy, strict weight management, and tailored educational and behavioral support improve outcomes. However, without proper intervention, obesity-related complications, such as type 2 diabetes, hypertension, and cardiovascular diseases, are common and can significantly reduce life expectancy.
