THE PRADER‐LABHART‐WILLI SYNDROME: REVIEW OF THE LITERATURE AND REPORT OF NINE CASES
Authors: Dunn. Henry G. 
Published: January 2008

In 1956 Prader and his associates described a syndrome of obesity, small stature, acromicria and oligophrenia, regularly preceded by an amyo‐tonic state in the newborn period. The males also had a hypoplastic flat scrotum, inguinal or abdominal retention of testes and delayed puberty. A tendency to the development of diabetes mel‐litus in the teenage years was also noted, and the diabetes was of the type normally encountered with onset at maturity rather than in childhood.

About 70 cases of this syndrome have been published to date. The literature is reviewed, and details concerning 9 patients of our own are given. Seven of these 9 are males; this predominance may be influenced by the fact that the hypogenitalism in boys facilitates the diagnosis. The mean parental ages at the birth of our patients were abnormally high, but this finding has not been encountered by other observers. Clinically, in addition to the features described by Prader and his colleagues, these patients presented a normal or somewhat large head circumference, delay in dentition and closure of the anterior fontanelle, marked dental caries often superimposed on defective enamel, a somewhat characteristic facies with fair or auburn hair and blue eyes, phimosis in boys, and strabismus. The dermatoglyphic pattern showed no consistent striking aberration but a low average total digital ridge count. The weight tended to be at least 1 SD below the mean during the first year and only became significantly high (above + 2 SD for height‐age) at a mean age of over 3 years, while growth did not accelerate. Behavioral development appeared to slow down during the pre‐school years, whereas the initial hypotonia and weakness improved.

The radiological bone age was retarded significantly in boys below the age of 4 years, but not in the one girl who was x‐rayed at that time. Electroencephalograms did not show any gross paroxysmal activity, but at times revealed dys‐rhythmic patterns. Eleetrodiagnostic studies and muscle biopsies did not indicate any abnormality of the lower motor neurone or muscles. Glucose tolerance tests in 8 patients showed a diabetic curve in one girl of 131/2 years and somewhat (but not significantly) high curves in 4 other children. On priming with steroid a boy of 41/2 years also gave a diabetic response. The fasting plasma levels of insulin in 7 cases were essentially normal; the levels after a glucose load appeared to rise abnormally high in the subclinically diabetic girl. Synalbumin insulin antagonist was found in only 1 out of 6 patients; it was also demonstrated in at least one healthy brother of that boy. Plasma growth hormone levels were normal in 5 children. The first case had an XYY chromosome abnormality, and two of seven others had minor chromosomal aberrations.

A variety of other biochemical investigations and detailed blood grouping were performed. The findings are discussed, and the possibility of a congenital structural or functional defect of the hypothalamus as an important component of the syndrome is considered. The mode of inheritance is not yet clear.