Prader Willi syndrome in infants symptoms causes and treatment methods

Prader-Willi syndrome is a rare genetic condition that appears from birth and affects a child’s growth and overall health. Early recognition of its symptoms and understanding the causes can help parents support their child in the right way and improve their quality of life. In this Dalily Medical article, we’ll explore the causes of Prader-Willi syndrome in infants, its symptoms, different stages, and the most important treatment and daily care strategies, so every parent can be prepared to support their child with love and awareness.

What is Prader-Willi Syndrome in children?

Prader-Willi Syndrome (PWS) is a rare genetic disorder that affects a child’s body, brain, and behavior. One of its most striking features is excessive appetite, where the child constantly feels hungry, usually starting around the age of two, and has difficulty feeling full.

But appetite isn’t the only sign — there are other symptoms parents should be aware of:

Symptoms of Prader-Willi Syndrome in Infants

1️⃣ Weak muscles (Hypotonia)

The baby has very weak muscles, appearing like a floppy doll.
Difficulty controlling arm and leg movements.
Trouble feeding due to weak sucking, which may lead to poor weight gain.

2️⃣ Distinct facial features

Almond-shaped eyes.
Thin upper lip with a downturned mouth.
Narrow temples.

3️⃣ Weak response

The baby may not respond easily to external stimuli.
Difficulty staying awake, paying attention, or even crying.

4️⃣ Underdeveloped genitals

Boys: small penis and scrotum, sometimes undescended testicles (cryptorchidism).
Girls: small labia and clitoris.

Symptoms After Weaning and During Childhood

1️⃣ Excessive appetite & obesity

Children eat compulsively and cannot control hunger.
Rapid weight gain due to slow metabolism.
Food-related behaviors, such as:
- Hiding or hoarding food in strange places.
- Eating frozen food without waiting.
- Eating food from the trash.

2️⃣ Hypogonadism (underactive sex glands)

Low production of sex hormones.
Delayed puberty signs, such as:
- Delayed or absent menstruation in girls without treatment.
- Lack of facial hair in boys and a childlike voice.

3️⃣ Thyroid dysfunction

Affects metabolism and growth.
Children may be short, with weak muscles and high body fat.

4️⃣ Developmental delays

Intellectual disabilities, difficulties with problem-solving and reasoning.
Delayed motor skills such as crawling and walking.

Additional Behavioral & Neurological Symptoms

Speech delay and difficulty pronouncing words: Children may struggle with expressing themselves clearly.
Temper tantrums and aggressive behavior: Often triggered when food is restricted or routines are changed.
Sleep disorders: Some children experience sleep apnea (temporary breathing pauses), affecting sleep quality.

Why does this happen to my child?

Dear parent, it’s completely normal to feel worried and overwhelmed with all these symptoms. But the scientific explanation is fairly clear:

???? Prader-Willi Syndrome is caused by an abnormality in chromosome 15 inherited from the father.

This genetic defect affects the hypothalamus in the brain — a region responsible for regulating many vital functions such as:

Hunger and satiety
Growth rate
Sleep cycles
Mood regulation
Body temperature

Causes of Prader-Willi Syndrome in Children

Prader-Willi Syndrome occurs due to the loss of function of certain genes located on chromosome 15.

When a baby is conceived, they inherit one copy of chromosome 15 from each parent. However, only the father’s copy is active, while the mother’s copy is “switched off.”
If there’s any problem in this process (called genomic imprinting), the syndrome develops.

The main genetic causes are:

1️⃣ Chromosomal Deletion

The most common cause (about 70% of cases).
Happens when part of the father’s chromosome 15 is missing, leaving only the inactive maternal copy.

2️⃣ Maternal Uniparental Disomy (UPD)

Accounts for about 25% of cases.
The child inherits two copies of chromosome 15 from the mother, instead of one from each parent — meaning both are inactive.

3️⃣ Imprinting Defect

The genes are present, but there is a problem in the way they are activated.
As a result, the father’s chromosome 15 doesn’t function as it should.

4️⃣ Rare Cases: Chromosomal Translocation or Rearrangement

Less than 1% of cases.
A piece of chromosome 15 moves to another chromosome, preventing the genes from working properly because they are out of place.

Types of Prader-Willi Syndrome in Children

Prader-Willi Syndrome results from genetic changes in chromosome 15. The specific type of change determines the subtype of the syndrome. The main types include:

1️⃣ Genetic Deletion

The most common type (about 70% of cases).
A section of chromosome 15 from the father’s side is missing.
This section contains important genes, and its loss leads to the syndrome’s symptoms.

2️⃣ Imprinting Defect

Chromosome 15 is present, but the paternal genes are not active.
Accounts for about 1–3% of cases.

3️⃣ Maternal Uniparental Disomy (UPD)

The child inherits two copies of chromosome 15 from the mother and none from the father.
Represents about 25% of cases.

Diagnosis of Prader-Willi Syndrome in Children

Diagnosis relies on clinical evaluation and matching symptoms to the National Institutes of Health (NIH) diagnostic criteria.

1. Criteria for children under 3 years

At least 4 major criteria + 1 minor criterion.

2. Criteria for children over 3 years

At least 5 major criteria + 3 minor criteria.

Major Clinical Criteria

Hypotonia (low muscle tone).
Weak suck reflex in infancy, which may improve after the first months.
Feeding difficulties or failure to thrive during the first year of life.
Rapid weight gain between ages 1–6 years, leading to obesity.
Uncontrollable hyperphagia (excessive eating).
Characteristic facial features: narrow forehead, downturned mouth, almond-shaped eyes.
Hypogonadism (underdeveloped genitals), leading to delayed puberty or infertility.
Global developmental delay before age 6 (e.g., sitting after 12 months, walking after 24 months).
Learning difficulties in older children, with an average IQ between 50–70.

Minor Clinical Criteria

Reduced activity and lethargy in infancy.
Behavioral problems: temper tantrums, obsessive-compulsive traits, stubbornness.
Sleep disorders: sleep apnea, excessive daytime sleepiness.
Short stature and delayed growth spurt during puberty.
Unusually fair skin, hair, and eyes.
Small hands and feet.
Eye problems such as strabismus or difficulty focusing together.
Thick, sticky saliva and cracked corners of the mouth.
Speech difficulties and problems forming words.
Skin picking or recurrent scratching.

Tests and Examinations for Diagnosing Prader-Willi Syndrome in Children

After evaluating the clinical symptoms, doctors turn to genetic tests and detailed examinations to confirm the diagnosis:

1️⃣ Genetic Testing

Detects changes in chromosome 15, which is responsible for Prader-Willi Syndrome.
Can also be performed prenatally in families with a history of the syndrome to assess the risk.

2️⃣ DNA Methylation Testing

The main genetic tool for confirming the diagnosis.
Identifies whether the paternal copy of chromosome 15 is missing or inactive.
Especially useful in infants who may not yet show the classic symptoms.

3️⃣ Fluorescent In Situ Hybridization (FISH)

Uses labeled DNA probes to detect specific genetic sequences.
Helps identify deletions in chromosome 15.
Cannot detect maternal uniparental disomy (UPD).

4️⃣ High-Resolution Microarrays

Determine the size of deletions in chromosome 15.
Can detect maternal UPD with high accuracy.
Important for classifying the type of genetic change, which helps guide treatment and follow-up.

Complications of Prader-Willi Syndrome in Infants

Prader-Willi Syndrome affects different aspects of a child’s development and health. Early diagnosis and medical follow-up are essential to minimize complications.

1. Growth and Development Issues

Severe muscle weakness (hypotonia) delays crawling, walking, and sitting.
Motor and cognitive developmental delay, requiring more time to master skills.
Short stature due to growth hormone deficiency.

2. Health Problems

Feeding difficulties in the first months due to weak oral muscles and poor sucking.
Reduced neurological responses, with slow reactions to stimuli.
Sleep disturbances, including breathing difficulties during sleep.

3. Eating and Weight-Related Problems

Excessive appetite (hyperphagia), typically starting around age 2.
Early obesity if a strict diet is not followed.
Metabolic disorders such as diabetes or high blood pressure later in life.

4. Behavioral and Psychological Issues

Tantrums and stubbornness, especially when denied food.
Learning difficulties and intellectual disabilities, ranging from mild to moderate.
Obsessive-compulsive behaviors related to food or routines, such as hoarding food or repetitive actions.

Stages of Prader-Willi Syndrome in Infants and Children

The symptoms vary with age, and recognizing the stages helps parents provide appropriate support:

1️⃣ Newborn Stage (0–6 months)

Severe hypotonia: baby feels very floppy, struggles with sucking and feeding.
Difficulty swallowing: some require tube feeding.
Low activity: excessive sleep and limited movement.
Digestive problems: constipation or slow digestion.

2️⃣ Late Infancy (6–12 months)

Continued muscle weakness, but gradual attempts to crawl or sit with support.
Slow weight gain due to feeding challenges.
Delayed motor skill development compared to healthy infants.

3️⃣ Early Childhood (1–3 years)

Poor muscle control, leading to difficulty walking independently or using hands.
Gradual increase in appetite.
Mild learning or concentration difficulties, requiring extra support.

4️⃣ Preschool Stage (3–6 years)

Hyperphagia (excessive appetite), with risk of severe obesity if diet is not controlled.
Persistent muscle weakness, leading to balance and walking problems; some may need mobility aids.
Compulsive behaviors or tantrums, often linked to food or changes in routine.

Symptoms of Prader-Willi Syndrome in Children

Prader-Willi Syndrome is caused by dysfunction in the hypothalamus, the brain region controlling hormones such as growth hormone, thyroid hormones, and sex hormones. This leads to muscle weakness, feeding difficulties, slow growth, excessive appetite, intellectual and behavioral challenges, and various physical symptoms that change with age.

From Birth to 1 Year

Hypotonia (floppy baby syndrome): weak muscles, difficulty sucking, poor weight gain.
Facial features: almond-shaped eyes, downturned mouth, thin upper lip, narrow temples.
Weak responses: baby seems tired, difficult to wake, low reaction to stimuli.
Strabismus (crossed eyes): difficulty moving eyes together.
Underdeveloped genitals:
- Boys → small penis and/or undescended testes.
- Girls → small clitoris and labia.

From 1 Year to Puberty – Symptoms of Prader-Willi Syndrome

A. Increased Appetite and Obesity

Strong food cravings usually begin around age 2.
The child does not feel full and constantly seeks food, leading to early obesity.
Unusual eating behaviors may appear, such as eating frozen food or even food from the garbage.

B. Underdeveloped Genital Organs (Hypogonadism)

Caused by a deficiency or absence of sex hormones.
Delayed puberty or failure to reach puberty; infertility is common in both sexes.
Girls may have a very late onset of menstruation, while boys may lack facial hair and voice changes.

C. Poor Growth and Physical Development

Growth hormone deficiency → short stature, low muscle mass, increased body fat.

D. Endocrine Disorders

Reduced thyroid and adrenal gland function → poor response to stress or infections.

E. Intellectual Disabilities and Learning Difficulties

Range from mild to moderate.
Problems with thinking, reasoning, and problem-solving.

F. Delayed Motor Development

Delays in sitting, crawling, and walking compared to healthy children.

G. Speech Problems

Delayed speech development and ongoing difficulty expressing words until puberty.

H. Behavioral and Psychological Problems

Stubbornness, tantrums, and poor mood regulation.
Repetitive behaviors, obsessive-compulsive tendencies, or mental health issues such as anxiety.

I. Sleep Disorders

Sleep apnea and disrupted sleep cycles → daytime sleepiness and worsening behavioral issues.

J. Additional Physical Signs

Small hands and feet, spinal curvature (scoliosis), and short stature.

Treatment of Prader-Willi Syndrome in Children

Currently, there is no cure for Prader-Willi Syndrome, but symptoms can be managed with a multidisciplinary healthcare team. Treatment aims to improve quality of life and control complications:

1️⃣ Managing Appetite and Behavioral Problems

Infants with weak muscles may need high-calorie formulas or feeding tubes.
Older children/adolescents: parents must set strict limits on food quantity and timing to prevent severe obesity.
A low-calorie balanced diet + regular exercise helps maintain a healthy weight.
Supplements (calcium, vitamin D) may be needed for bone health.
In cases of food stealing or hoarding → parents may need to lock refrigerators/cupboards.

2️⃣ Hormone Therapy

Growth hormone → improves height, muscle mass, and reduces fat.
Testosterone (boys) or Estrogen (girls) → supports sexual development and prevents delayed puberty.
Helps strengthen bones and reduce risk of osteoporosis.

3️⃣ Antidepressants (if needed)