Question:

A 4-year-old boy is brought to the physician for evaluation of binge-eating. He complains constantly of hunger and has temper tantrums when his parents refuse to give him additional snacks. Past medical history is significant for hospitalization during the first month of life for nasogastric feeding due to weak suck and hypotonia. The patient is status post orchiopexy for bilateral cryptorchidism at age 1 year. He also receives physical and speech therapies twice a week. His height is <5th percentile and weight is >99th percentile. On examination, he has a narrow forehead, a down-turned mouth, almond-shaped eyes, and small hands and feet. He has low muscle tone and a microphallus.

Which of the following is the most likely cause of this patient's condition?

A. Disregulation of imprinted gene expression in chromosome 11p15

B. Loss of the maternal copy of 15q11-q13

C. Loss of the paternal copy of 15q11-q13

D. Nondisjunction resulting in an extra X chromosome

E. X-linked mutation of the fragile X mental retardation 1 gene

F. X-linked mutation of the hypoxanthine-guanine phosphoribosyl transferase gene

Answer: C. Loss of the paternal copy of 15q11-q13

This child presents with several signs suggestive of Prader-Willi syndrome (PWS).

• PWS is caused by the loss of the paternal copy of the 15q11-q13 region 

Loss of the paternal copy of 15q11-q13 region
⬇️
Absence of expression of key imprinted genes (e.g., SNRPN)
⬇️
Hypothalamic dysfunction
⬇️
🧠 Impaired regulation of hunger and satiety signals
⬇️
Constant hunger (hyperphagia)
⬇️
Binge eating and temper tantrums when denied food
⬇️
🧠 Decreased muscle tone (hypotonia)
⬇️
Poor motor development and coordination
⬇️
Short stature and small hands/feet
⬇️
🧠 Developmental delays and intellectual disability
⬇️
Difficulties in speech and motor function
⬇️
🧠 Endocrine dysfunction
⬇️
Hypogonadism (low sex hormone levels)
⬇️
Obesity due to metabolic dysfunction
⬇️
🧠 Facial features
⬇️
Narrow forehead, almond-shaped eyes, downturned mouth, microphallus

Behavioral Issues
⬇️
Temper tantrums, compulsive behaviors
⬇️
🧠 Uncontrolled eating behaviors and poor satiety regulation

Explanation of Other Answers

A. Loss of the maternal copy of 15q11-q13 (Angelman syndrome)
⬇️
🧠 Angelman syndrome features: Happy demeanor, developmental delay, seizures, no hyperphagia
⬇️
No hunger issues or temper tantrums seen in Angelman syndrome

B. Disregulation of imprinted genes in 11p15 (Beckwith-Wiedemann syndrome)
⬇️
🧠 Beckwith-Wiedemann syndrome features: Overgrowth, macroglossia, abdominal wall defects, not hyperphagia
⬇️
No obesity or hunger dysregulation in Beckwith-Wiedemann syndrome

D. Nondisjunction resulting in extra X chromosome (Klinefelter syndrome)
⬇️
🧠 Klinefelter syndrome features: Tall stature, hypogonadism, gynecomastia, no hyperphagia or hypothalamic dysfunction
⬇️
Not associated with the signs seen in this patient

E. X-linked mutation of fragile X gene
⬇️
🧠 Fragile X syndrome features: Intellectual disability, large ears, long face, no hyperphagia or hypotonia
⬇️
Not associated with overeating or hypotonia in the same way

F. X-linked mutation of hypoxanthine-guanine phosphoribosyl transferase gene (Lesch-Nyhan syndrome)
⬇️
🧠 Lesch-Nyhan syndrome features: Self-mutilation, uric acid overproduction, neurological issues
⬇️
No hyperphagia or obesity in Lesch-Nyhan syndrome

Flashcards

Stay Hungry, Stay Curious!

Your Brother In This Struggle,

Dr. Shoaib Ahmad