Prader Willi Syndrome: What is it? Causes, Symptoms, Diagnosis, Risk Factors and Treatment

It is a genetic condition that can affect muscle tone, sexual development, and nervous system function.

In addition, people with Prader-Willi syndrome are more likely to have learning difficulties.

Often, it also awakens a constant desire to eat food and a permanent feeling of hunger.

Prader-Willi syndrome is a complex genetic condition that affects many body parts. This condition is characterized by weak muscle tone ( hypotonia ), feeding difficulties, poor growth, and developmental delay in infancy.

From infancy, affected people develop an insatiable appetite, which leads to chronic overeating ( hyperphagia ) and obesity. Some people with Prader-Willi syndrome, particularly those with obesity, also develop type 2 diabetes (the most common form of diabetes).

People with Prader-Willi syndrome generally have mild to moderate intellectual impairment and learning disabilities.

Behavioral problems are common, including outbursts of temper, stubbornness, and compulsive behavior, such as pinching the skin. Sleep abnormalities can also occur.


Additional features of this condition include distinctive facial characteristics such as a narrow forehead, almond-shaped eyes and a triangular mouth, short stature, and small hands and feet.

Some people with Prader-Willi syndrome have white skin and light hair. Both affected men and affected women have underdeveloped genitalia.

Puberty is delayed or incomplete, and most affected people can not have children (infertile).

Prader-Willi syndrome is caused by the loss of function of genes in a particular region of chromosome 15. People usually inherit a copy of this chromosome from each parent.

Some genes are activated only in the copy inherited from the father of a person (the paternal copy). This specific genetic activation for parents is caused by genomic imprinting.

Most cases of Prader-Willi syndrome (about 70 percent) occur when a segment of paternal chromosome 15 in each cell is removed.

People with this chromosomal change lack specific critical genes in this region because the genes in the paternal copy have been deleted, and the genes in the maternal copy are deactivated (inactive).

In another 25 percent of the cases, a person with Prader-Willi syndrome has two copies of chromosome 15 inherited from his mother (copies of the mother) instead of a copy of each father. This phenomenon is called maternal uniparental disomy.

Rarely, Prader-Willi syndrome can also be caused by a chromosomal rearrangement called translocation or by a mutation or other defect that abnormally turns off (inactivates) the genes in the paternal chromosome 15.

It seems likely that the characteristics of Prader-Willi syndrome result from the loss of function of several genes on chromosome 15.

The genes that provide instructions for creating molecules called small nucleolar RNAs (snoRNAs) are among these.

These molecules have a variety of functions, including helping to regulate other types of RNA molecules. (RNA molecules play essential roles in the production of proteins and other cellular activities).

Studies suggest that the loss of a particular group of snoRNA genes, known as the SNORD116 group, may play an essential role in causing the signs and symptoms of Prader-Willi.

However, it is not known how a missing SNORD116 cluster could contribute to the intellectual disability, behavioral problems, and physical characteristics of the disorder.

In some people with Prader-Willi syndrome, the loss of a gene called OCA2 is associated with white skin and light-colored hair.

The OCA2 gene is found in the segment of chromosome 15, often eliminated in people with this disorder. However, loss of the OCA2 gene does not cause the other signs and symptoms of Prader-Willi syndrome.

The protein produced from this gene helps determine the coloration (pigmentation) of the skin, hair, and eyes.

Researchers are studying other genes on chromosome 15 that may also be related to this condition’s main signs and symptoms.

Most cases of Prader-Willi syndrome are not inherited, particularly those caused by a deletion on the father’s chromosome 15 or by maternal uniparental disomy.

These genetic changes occur as random events during the formation of reproductive cells or in early embryonic development. Affected people usually have no history of the disorder in their family.

Rarely a genetic change responsible for Prader-Willi syndrome can be inherited. For example, a genetic change that abnormally inactivates genes in the paternal chromosome 15 may be passed from one generation to another.


Those with SPW have a genetic defect on chromosome number 15. In about 70 percent of cases, part of the DNA information inherited from the father is missing, which is known as “parental elimination.”

Other cases occur when a child has two copies of his mother and none of his father. The condition is obtained by pure chance, but those with a child with PWS have less than a 1% chance that the next one will be affected.

How is Prader-Willi syndrome diagnosed?

Genetic tests are used to diagnose Prader-Willi syndrome. Medical professionals will often carry out this check if they identify someone who shows the symptoms of Prader-Willi syndrome.


The Prader-Will Syndrome Association describes the medical characteristics of the condition as:

Hypotonia: weak muscle tone and looseness at birth.

Hypogonadism: immature development of sexual organs and other sexual characteristics.

Obesity: is caused by an excess of appetite and overeating (hyperphagia) and a reduced caloric requirement due to low levels of energy expenditure. However, obesity is not usually a characteristic of those whose food intake is strictly controlled.

Dysfunction of the central nervous system and the endocrine gland: causes various degrees of learning disability, short stature, hyperphagia, drowsiness (excessive sleepiness), and deficient emotional and social development.

Risk factor’s

Because children with Prader-Willi syndrome can consume three to six times more food than other children of the same age, there is a significant risk of obesity. Compulsive food consumption can also cause your stomach to expand abnormally.

Young adults diagnosed are also at risk for type 2 diabetes and heart failure if they do not control their diet.


As it is currently, there is no cure for Prader-Willi syndrome. Those diagnosed with the condition are encouraged to take measures to reduce the severity of the symptoms and associated problems.

Parents of children are asked to control any excessive intake and try to keep balanced and healthy meals on the menu.


Patients with Prader-Willi syndrome often require medical attention for the following:

  • Initial management of hypotonia or poor diet.
  • Evaluation of hypogonadism or hypopituitarism.
  • Management of obesity.
  • Monitoring of scoliosis.
  • Therapy for behavior problems.

Patients with Prader-Willi syndrome may require surgical care for the treatment of complications of obesity, treatment of cryptorchidism, and the intervention of scoliosis.

They may require urgent surgical care for abdominal problems. Due to the high tolerance to pain and the lower capacity to vomit, they may present late with symptoms of cholecystitis, appendicitis, or acute gastric dilation with a risk of progression to necrosis.

The tonsillectomy, adenoidectomy, or tracheostomy placement may be necessary for patients with obstructive sleep apnea.


Prader-Willi syndrome is the first human disorder attributed to genomic imprinting. In such conditions, the genes are differentially expressed depending on the father of the origin.

A printing center has been identified within 15q11-13; Gene expression may be regulated by DNA methylation on cytosine bases. Prader-Willi syndrome results from the loss of genomic material printed at the paternal 15q11.2-13 locus.

The loss of maternal genomic material at locus 15q11.2-13 results in Angelman syndrome.

Most cases of Prader-Willi syndrome involving deletions, unbalanced translocations, and uniparental (maternal) disomy are sporadic. The monozygotic twins have been affected accordingly.

Approximately 70% of the cases of Prader-Willi syndrome arise from the elimination of the 15q11-13 band on chromosome 15. Maternal uniparental disomy caused by chromosomal non-disjunction represents 28% of the cases of Prader syndrome. Willi

Less than 1% of patients have mutations isolated from the printing center, which entails a risk of recurrence. Some experts have suggested that the eliminations only located in the printing center may be due to the lack of elimination of the maternal impression during spermatogenesis.

Several genes have been mapped in the 15q11.2-13 region, including the SNRPN gene, the P gene (oculocutaneous albinism type II), the UBE3A gene (it encodes a ubiquitin-protein ligase involved in intracellular protein turnover) and the gene necdin (codes for a nuclear protein expressed exclusively in the brain of differentiated mice).

Mutations associated with the maternal UBE3A gene result in Angelman syndrome.

The role of ghrelin in the satiety defect found in Prader-Willi syndrome is a subject of active research.

Morbidity and Mortality

The main contributors to morbidity and mortality in individuals with Prader-Willi syndrome are complications due to obesity (e.g., slipped capital femoral epiphyses, sleep apnea, type 2 diabetes mellitus) and behavioral problems.

Experts reported the early development of atherosclerosis with severe coronary artery disease in a 26-year-old patient with Prader-Willi syndrome, morbid obesity, and non-insulin-dependent diabetes mellitus.

They also described a series of 6 patients with Prader-Willi syndrome with dramatic acute gastric distension preceded by symptoms of gastroenteritis. Half of the cases progressed rapidly to massive gastric dilatation and gastric necrosis.

One patient died of overwhelming sepsis and disseminated intravascular coagulation. Gastric dilation resolved spontaneously in 2 children. The gastrectomy was performed in 2 patients; in one patient, gastrectomy was subtotal and distal, while in the other patient, gastrectomy was combined with partial duodenectomy and pancreatectomy.

A series of autopsies by Stevenson and Cols reported gastric rupture and necrosis as the confirmed cause of death in 3% of patients with Prader-Willi syndrome, with four other suspected cases of gastric necrosis.

In a series of 152 patients with Prader-Willi syndrome, choking episodes were reported as the cause of death in 7.9%.

Another series of patients noticed eight children and two adults who had unexpected death, with small adrenal glands observed in 3 of 8 children, which generated suspicion of underlying adrenal insufficiency.

Subsequent studies have questioned the frequency of central adrenal insufficiency proposed by these authors, believing it to be a rare occurrence.