Prader Willi Syndrome: Symptoms, Causes, Treatment

The Prader-Willi Syndrome ( PWS ) is a multisystem disease that has a genetic origin of congenital type. It is a complex disease that affects appetite, growth, metabolism, behavior and / or cognitive function.

At the clinical level, during the childhood stage, this disease is characterized by the presence of various medical findings such as muscle weakness, eating disorders or generalized developmental delay.

Prader Willi syndrome

In addition, at the cognitive and behavioral level, a good part of the individuals affected by Prader-Willi syndrome present a moderate intellectual impairment or delay that is accompanied by various learning and behavior problems.

Despite the fact that 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. The diagnosis of this disease is made mainly on the basis of clinical findings and complementary genetic tests.

Regarding treatment, a cure for Prader-Willi syndrome has not yet been identified, so the therapeutic approach is oriented towards treating the symptoms and complications, with obesity being the medical finding that poses the greatest threat to those affected .

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.


Different clinical reports indicate that Prader-Willi syndrome (PWS) was initially described by JL Down, in 1887, after diagnosing one of his patients with “polysarcia”. 

However, it was Drs Prader, Labhart and Willi who, in 1956, described another 9 cases and gave this pathology its name. Furthermore, the characteristics and diagnostic criteria of Prader-Willi syndrome were systematized by Holm et al.


Prader-Willi syndrome is a congenital genetic alteration, that is, it is a pathology that is present from the moment of birth and will affect the individual throughout his life if there is no curative therapeutic intervention.

This pathology presents a complex clinical course, characterized by numerous medical manifestations.

Although the phenotype of Prader-Willi syndrome is more precisely known today, it has been in the last 25 years that significant progress has been made in the analysis and understanding of this disease.

The expression of Prader-Willis syndrome is diverse, it tends to affect multiple systems and structures, most of the alterations being related to hypothalamic dysfunction.

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.

In addition, the hypothalamus releases different hormones to various glands: growth, sexual, thyroid, etc.

Finally, we must point out that Prader-Willis syndrome may also appear referenced in the medical and experimental literature with other terms such as Prader-Labhart-Willi syndrome or with the acronym PWS.

Also, other synonyms are Labhart Willi syndrome, Praser Labhart Willi Fancone syndrome, or hypogenital dystrophy syndrome.


Prader-Willi syndrome (PWS) is a rare genetic disease. The term rare disease (ER) is used to refer to those pathologies that are rare or few people who suffer from it.

Currently, it is estimated that Prader-Willi syndrome is a pathology with a frequency of approximately 1 case per 10,000-30,000 people worldwide.

On the other hand, regarding the distribution by sex, it has been observed that this pathology affects men and women equally, and it is not associated with ethnic groups or geographic regions.

In addition, Prader-Willi syndrome is considered the main cause of obesity of genetic origin.

Signs and symptoms

At a clinical level, Prader-Willi syndrome has traditionally been associated with neonatal hypotonia, hypogonadism, hyperphagia, obesity, short stature, generalized delay in development, moderate intellectual disability, atypical facial appearance and different behavioral alterations.

Despite this, the clinical expression of this pathology is very heterogeneous and varies significantly among affected individuals.

In addition, the characteristic signs and symptoms of Prader-Willi syndrome tend to vary with biological development, so we can observe different clinical findings in the fetal and neonatal period, the period of infancy or early childhood, school stage and finally, the stage Teen.

In a systematic way, José A. del Barrio del Campo and collaborators, describe in detail the most characteristic alterations in the biomedical, psychomotor, cognitive and behavioral area:

-Biomedical manifestations

The most characteristic physical signs and symptoms include disturbances such as; hypotonia, musculoskeletal malformations or 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.


Presence or development of reduced muscle tone. Muscle flaccidity in this pathology is especially accentuated 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.

Musculoskeletal deformities or malformations

In this case, it is common to observe the development of scoliosis or deviation of the spine, a poor alignment of the lower limbs (genu valgus) or the presence of flat feet.

In addition, other types of congenital anomalies can also be observed, such as reduction in the size of the feet and hands, hip dysplasia, presence of six fingers, among others.

Low weight and height

Especially at the time of birth, both the height and weight of the affected child is lower than expected for their development and sex. Although standard values ​​can be reached in adulthood, the slow growth rate tends to alter adult values ​​of height and weight.

Excess appetite and obesity

It is common to observe in people with Prader-Willi syndrome an insatiable appetite, characterized by an obsession or fixation on food. Due to the intake of large amounts of food, those affected tend to develop obesity and other associated medical complications, such as type II diabetes mellitus.


The presence of genital alterations is also frequent. Specifically, hypogonadism or partial development of the external genitalia is very common. In most cases, pubertal development fails to reach the final or adult stages.

Respiratory disorders and alteration of sleep-wake cycles:

Snoring, increased frequency or respiratory arrest often appear recurrently during sleep phases. Thus, those affected tend 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 craniofacial features. It is possible to observe a narrow skull, eye strabismus, poorly pigmented skin and hair, small mouth and thin lips, dental malformations, etc.

Altered regulation of body temperature

People affected by Prader-Willi syndrome often have problems related to the regulation of body temperature, and another significant finding is high resistance to pain.

-Psychomotor and cognitive manifestations

Psychomotor manifestations

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

Those affected usually present series difficulties to carry out any type of activity that requires one or more 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 more affected such as the sequential processing of information,  recent or short-term memory , solving arithmetic problems, auditory processing of verbal information, alteration of attention and concentration and presence of cognitive rigidity.

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

-Behavioral manifestations

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

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

Various current investigations have indicated that behavioral alteration tends to increase with age and, therefore, has a worsening, affecting social, family and emotional areas in a generalized way.


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

Although there is currently a great controversy about the specific genes responsible for this pathology, all the data show that the etiological alteration is located on chromosome 15.

Throughout the genetic study of this pathology, there have been several contributions. Burtler and Palmer (1838) detected the presence of abnormalities 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 genes of paternal expression that are located in the 15q11-13 region of chromosome 15.


The diagnosis of Prader-Willi syndrome has two basic components, the analysis of clinical findings and genetic testing.

Regarding the detection of the indicator signs and symptoms, both in babies and in older children, it will be essential to carry out a detailed, individual and family medical history. Likewise, it is also essential to carry out 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 genetic alterations and abnormalities.

Specifically, around 90% of cases are definitively diagnosed through DNA methylation tests and other additional tests.

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

Specifically, the amniocentesis test allows the extraction of embryo samples for the performance of the relevant genetic tests.


There is currently no cure for Prader-Willi syndrome. As in other rare diseases, treatments are limited to symptom control and improving the quality of life of the affected people.

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

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.


  1. AWSPW. (2016). What is prader Willi syndrome? Spanish Association Prader-Willi Syndrome .
  2. Campubrí-Sánchez, C., Gabau-Vila, E., Artigas-Pallarés, J., Coll-Sandiumenge, M., & Guitart-Feliubadaló, M. (2006). From clinical diagnosis to genetic diagnosis of Prader-Willi and Angelman syndromes. Rev Neurol , 61-67.
  3. del Barrio del Campo, J., Castro Zubizarreta, S., & San Román Muñoz, M. (2008). Chapter VIII. Prader-Willi syndrome.
  4. FPWR. (2016). About PWS . Obtained from Foundation for Prader-Willi Research.
  5. Rosell-Raga, L., & Venegas-Venegas, V. (2006). Autistic symptomatology and Prader Wili syndrome. Rev Neurol , 89-93.
  6. Solà-Aznar, J., & Giménez-Pérez, G. (2006). Comprehensive approach to Prader-Willi syndrome in adulthood. Endocrinol Nutr , 181-189.

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