Disorder characterized by early childhood-onset morbid obesity, infantile hypotonia, short stature, hypogonadism, and mental retardation. Diabetes mellitus usually develops in childhood. Most patients present with Sleep Apnea Syndrome.
Prader-Willi Syndrome; Willi-Prader Syndrome.
First described in 1956 by A. Prader, A. Labhart, and H. Willi, all three Swiss pediatricians and internists, on the basis of observation obtained from nine children with the tetrad of short stature, mental retardation, severe obesity, and small hands and feet. In 1961, muscle hypotonia in infancy was added to the phenotype.
In the United States, most cases are sporadic in occurrence. Prevalence 1:10,000 to 1:25,000.
Most cases arise sporadically. Syndrome results from the loss of the paternal copy of chromosome 15q11.2-13. It is described as a microdeletion/disomy disorder. More than 70% of patients have a deletion of the paternal copy. Approximately 25% of patients have maternal uniparental disomy for chromosome 15. The remainder present with translocation or other structural aberration in chromosome 15.
The major neuroendocrine phenotypes of this syndrome are likely due to hypothalamic dysfunction and defects in prohormone processing leading to hyperphagia. Morbid obesity leads to reduction in lung volumes, including expiratory reserve volume, vital capacity, and functional residual capacity; closing capacity is increased, leading to airway closure in the dependent areas of the lung and V/Q mismatch; reduced chest and diaphragmatic excursions; decreased alveolar ventilation; diminished sensitivity of the respiratory center to hypoxia and hypercarbia—all contributing to hypoxia and hypercarbia. Intermittent upper airway obstruction and hypoxia during sleep with resultant chronic sleep deprivation and daytime somnolence; severe and chronic hypoxia leading to polycythemia, pulmonary hypertension, right ventricular hypertrophy, and failure.
Neonatal hypotonia is one hallmark feature of this disorder and is a valuable clue to initiate diagnostic testing. Clinical features; biochemical (polycythemia, hypoxia, hypercarbia); lung function tests (reduced lung volumes including total lung capacity, functional residual capacity, vital capacity, and expiratory reserve volume); ECG (right axis deviation); chest radiograph or echocardiography (cardiomegaly); sleep studies (obstructive sleep apnea).
The syndrome is biphasic; initially the picture is one of hypotonia and later changes to hyperphagia leading to obesity.
Antenatal: Delayed onset and reduced fetal activity during pregnancy; often breech presentation at birth.
Neonatal and infancy: Low birth weight, infantile hypotonia (“floppy infant”), neonatal asphyxia, poor feeding, and failure to thrive; gross motor developmental delay, weak cry and cough, hypogonadism with genital hypoplasia. Neonates may require tube feeding for 3 to 4 months, although this usually improves by 6 months and by 12 to 18 months, uncontrollable hyperphagia occurs.
Childhood: Endocrine (polyphagia, insatiable hunger, hypoglycemia, rapid weight gain after 1 year of age, morbid obesity, ...