Prader Willi Syndrome: Symptoms, Causes, Treatment

The Prader-Willi Syndrome ( PWS ) is a multisystem disease that has a genetic type of congenital (National Organization for Rare Disorders, 2012). It is a complex disease that affects appetite, growth, metabolism, behavior and / or cognitive function (USA Prader-Willi Syndrome Association, 2016).

At the clinical level, during childhood, this disease is characterized by the presence of various medical findings such as muscle weakness, alterations in diet or generalized developmental delay (Genetics Home Reference, 2016).

Prader Willi Syndrome Symptoms

In addition, at the cognitive and behavioral level, many of the individuals affected by the Prader-Willi syndrome present moderate intellectual deterioration or retardation  , which is accompanied by various learning and behavior problems (Genetics Home Reference, 2016).

Although Prader-Willi syndrome is considered a rare or uncommon disease, numerous studies indicate that it is one of the most frequent pathologies  in the genetic area (USA Prader-Willi Syndrome Association, 2016).

The diagnosis of this disease is mainly based on clinical findings and complementary genetic tests (Foundation for  Prader-Willi Research, 2014).

Regarding treatment, a cure for Prader-Willi syndrome has not yet been identified, so the therapeutic approach is aimed at  treating symptoms and complications, with obesity being the medical finding that poses the greatest threat to the treatment. those affected (National  Institutes of Health, 2016).

Thus, in relation to prognosis and quality of life, both will depend on the severity of the associated medical problems and the behavioral or cognitive disorders  that may develop (Campubrí-Sánchez et al., 2006).

Characteristics of Prader-Willi syndrome (SPW)

Different clinical reports indicate that Prader-Willi syndrome (PWS) was initially described by JL Down, in 1887, after diagnosing  one of his “polisarcia” patients (Solà-Aznar and Giménez-Pérez, 2006). ).

However, it was Drs Prader, Labhart and Willi who, in 1956, described another 9 cases and gave name to this pathology  (Rossel-Raga, 2003).

In addition, the characteristics and diagnostic criteria of the Prader-Willi syndrome were systematized by Holm et al. (Campubrí-Sánchez et al.,  2006).

The Prader-Willi syndrome is a congenital genetic disorder, that is, it is a pathology that is present from the moment of birth and  will affect the individual throughout his or her life if there is no curative therapeutic intervention (Asociación Española Prader- Willi, 2016).

This pathology presents a complex clinical course, characterized by numerous medical manifestations (Campubrí-Sánchez et al., 2006).

Although, at present, the Prader-Willi syndrome phenotype is known more precisely (Campubrí-Sánchez et al., 2006), it has been in the last  25 years, when there has been a significant progress in the @nalysis and understanding of this disease (Solà-Aznar and Giménez-Pérez, 2006).

The expression of the Prader-Willis syndrome is diverse, tending to affect multiple systems and structures, most of the alterations being related  to a hypothalamic dysfunction (Poyatos et al., 2009).

The hypothalamus is a neurological structure that has an essential role in the control of homeostatic functions: the regulation of hunger,  thirst, sleep-wake cycles or the regulation of body temperature (Rosell-Raga, 2003) .

In addition, the hypothalamus releases different hormones to various glands: growth, sexual, thyroid, etc. (Rosell-Raga, 2003).

Finally, we should point out that the Prader-Willis syndrome can also be referenced in the medical and experimental literature with other terms such  as Prader-Labhart-Willi syndrome or with the acronym PWS (National Organization for Rare Disroders, 2012).

In addition, other synonyms are: Labhart Willi Syndrome, Praser Labhart Willi Fancone Syndrome or Hypogenital Dystrophy Syndrome (del Barrio del Campo  et al., 2008)


Prader-Willi syndrome (PWS) is a rare genetic disease (Orphanet, 2007).

The term Rare Disease (ER), is used to refer to those pathologies that are rare or that are rare people who suffer from it  (Spanish Association Prader-Willi Syndrome, 2016).

Currently, it is estimated that Prader-Willi syndrome is a pathology with an approximate frequency of 1 case per 10,000-30,000 people  worldwide (Genetics Home Reference, 2016).

On the other hand, in terms of gender distribution, it has been observed that this pathology affects both men and women equally, and is not  associated with ethnic groups or geographical regions (National Organization for Rare Disroders, 2012).

In addition, Prader-Willi syndrome is considered the main cause of obesity of genetic origin (Poyatos et al., 2009).

Signs and symptoms

At the clinical level, Prader-Willi syndrome has traditionally been associated with neonatal hypotonia, hypogonadism, hyperphagia, obesity, short stature,  generalized developmental delay, moderate intellectual disability, atypical facial appearance and different behavioral alterations (Poyatos  et al. ., 2009).

Despite this, the clinical expression of this pathology is very heterogeneous and varies significantly among affected individuals (Poyatos et al.,  2009).

In addition, the signs and symptoms characteristic of Prader-Willi syndrome have to vary with biological development, so we can observe  different clinical findings in the fetal and neonatal period, lactation period or early childhood, school stage and finally, the stage adolescent  (from the Barrio del Campo et al., 2008).

In a systematic way, José A. del Barrio del Campo et al. (2008) describe in detail the most characteristic alterations of the  biomedical, psych0m0tor, cognitive and behavioral areas:

Biomedical manifestations

The most characteristic physical signs and symptoms include alterations such as; hypotonia, malformations or musculoskeletal deformities, reduced or low weight and  height, excess appetite, obesity, hypogonadism, sleep disturbances, respiratory disorders, atypical easy traits, alteration  in the regulation of body temperature, among others.

  • Hypotonia : presence or development of a reduced muscle tone. The muscular flaccidity in this pathology is especially pronounced in  the neck and trunk, especially in the neonatal stage and the first months of life. Thus, with biological development, muscle tone tends to improve.
  • Deformities or musculoskeletal malformations: in this case, it is common to observe the development of scoliosis or deviation of the  spine, a deficient alignment of the lower limbs (genu valgo) or the presence of flat feet. In addition, another type of congenital anomalies can also be observed,  such as a reduction in the size of the feet and hands, dysplasia in the hip, presence of six fingers, among others.
  • Low weight and height: especially at the time of birth, both the height and the weight of the affected child is less than expected  for their development and sex. Although standard values ​​can be reached in adulthood, the reduced growth rate tends to alter  adult values ​​of height and weight.
  • Excess of appetite and obesity: it is common to observe in people suffering from Prader-Willi syndrome an insatiable appetite,  characterized by an obsession or fixation by food. Due to the ingestion of large amounts of food, those affected have to develop  obesity and other associated medical complications, such as diabetes mellitus type II.
  • Hypogonadism: the presence of genital alterations are also frequent. Specifically, hypogonadism or partial development of  the external genitalia is very frequent. In most cases, pubertal development fails to reach the final stages or adults.
  • Respiratory disorders and alteration of sleep-wake cycles: snoring, increased frequency or  respiratory arrest usually appear recurrently during the phases of sleep. Thus, those affected have to present various alterations related to  fragmentation, sleep delay or the presence of periodic awakenings.
  • Atypical facial features: Musculoskeletal abnormalities and malformations can also affect the cranio-facial features. It is  possible to observe a narrow skull, ocular strabismus, skin and pigmented hair, small mouth and thin lips, dental malformations, etc …
  • Alteration of body temperature regulation: People affected by Prader-Willi syndrome usually present problems  related to the regulation of body temperature, in addition another significant finding is the high resistance to pain.

Psych0m0tor and cognitive manifestations

Psych0m0tor manifestations

Due to the presence of musculoskeletal malformations and a reduced muscle tone, psych0m0tor development  will be slower, affecting all areas.

Those affected tend to have a series of difficulties to perform any type of activity that  requires one or several motor executions.

Cognitive manifestations

Regarding cognitive limitations, most of those affected have a mild or moderate intellectual disability  .

In addition to this, they usually present some specific areas most affected, such as sequential processing of information,  recent or short-term memory, the resolution of arithmetic problems, auditory processing of verbal information, alteration of attention and  concentration and the presence of cognitive rigidity.

On the other hand, language is another of the areas that are significantly affected in individuals suffering from Prader-Willi syndrome. Delays in the acquisition of phonological skills, poor vocabulary, alteration of grammatical construction, among others, are often  observed.

Behavioral manifestations

Problems and behavioral alterations are another of the typical findings that can be observed in Prader-Willi syndrome, usually have to  vary depending on the age or maturational stage in which the affected person is, however, some of the The most common behavioral traits  are:

  • Tantrums or irritability.
  • Poor social interaction.
  • Obsessive disorders
  • Aggressive behavior
  • Psychotic signs and symptoms.

Several current investigations have indicated that behavioral alteration tends to increase with age and, therefore, they have to aggravate, affecting  social, family and emotional areas in a generalized manner (Rosell-Raga, 2003).


As we have pointed out in several sections above, Prader-Willi syndrome has a genetic origin.

Although currently, there is great controversy about the specific genes responsible for this pathology, all data show that the etiological alteration  is located on chromosome 15 (Mayo Clinic, 2014)

Throughout the genetic study of this pathology, several contributions have been made. Burtler and Palmer (1838) detected the presence of anomalies in the  long arm of chromosome 15 from the paternal parent, while Nicholls (1989) observed that in other cases the disorder was related to  chromosomal alterations from the mother (Rosell-Raga , 2003).

Apart from this, the most accepted theory about the origin of this pathology is the loss or inactivation of various paternal expression genes that are  located in the 15q11-13 region of chromosome 15 (Poyatos et al., 2009).


The diagnosis of Prader-Willi syndrome has two basic components, the @nalysis of clinical findings and genetic tests.

With regard to the detection of indicator signs and symptoms, both in infants and in older children, it will be essential to carry out a detailed medical history  , individual and family. Likewise, it is also essential to perform a physical and neurological examination.

If based on these procedures, there is a diagnostic suspicion, it will be necessary to prescribe various complementary tests to determine the  presence of alterations and genetic anomalies.

Specifically, around 90% of cases are diagnosed definitively through DNA methylation tests and other additional tests  (National Organization for Rare Disorders, 2012).

In addition, it is also possible to perform a prenatal diagnosis of this medical condition, mainly in families that have a previous history  of Prader-Willi syndrome.

Specifically, the amniocentesis test allows the extraction of embryo samples to carry out the relevant genetic tests  (National Organization for Rare Disorders, 2012).


Currently, there is no cure for Prader-Willi syndrome. As in other rare diseases, the treatments are limited to the symptomatic control  and the improvement of the quality of life of the affected people.

However, one of the fundamental aspects will be nutritional control and nutrition, since obesity is the main cause of morbidity and  mortality in this pathology.

Also Read: Types of Seizures: Generalized vs. Focal

On the other hand, the presence of cognitive and behavioral alterations will require the intervention of specialized professionals both in cognitive rehabilitation  and in the management of conduct disorder.