Not long ago, 5-year-old Xiao Ming came to the endocrine genetic metabolism department of Zhengzhou Children’s Hospital with “obesity, mental retardation, irritability and small penis”. After asking about his medical history, we found that after birth, Xiao Ming had a weak cry, feeding difficulties, weak limbs and slow weight gain. 1 year old, his appetite improved, he ate a lot and was easily irritated, and his weight increased rapidly, by 4-6 kg per year. After careful examination and genetic diagnosis, Prader-Willi syndrome (PWS) was finally diagnosed after hospitalization.
Prader-Willi syndrome was first reported and named by Prader and Willi in 1956, with variable reports of birth prevalence, and is a common genetic syndrome causing obesity in humans. It is usually associated with deletion of fragment q11-13 imprinted on chromosome 15. Early diagnosis and treatment have a better prognosis; delayed diagnosis often leads to obesity syndrome and death around puberty, often due to complications such as diabetes and cardiac insufficiency from excessive obesity. The disease is often misdiagnosed in infancy as cerebral palsy, metabolic disease, hereditary myopathy, and severe malnutrition, and many children are hospitalized for long periods of time for rehabilitation, but with no efficacy. In childhood, it is often neglected by parents and treated only as a general obesity disease, etc. Therefore, it is important to enhance the knowledge and education about this disease.
The main diagnostic criteria of PWS include: overeating, centripetal morbid obesity, mental deficiency, behavioral abnormalities, short stature and gonadal dysgenesis, and genetic screening suggesting deletion of the 15 q11-13 fragment imprint, which is the basis for clinical confirmation. The disease can develop in both sexes. The disease has different clinical manifestations in different developmental stages: (1) fetal and perinatal period: low fetal movement, high rate of difficult breech delivery or cesarean section, low muscle tone (floppy babies) after birth, weak cry, tube feeding, sticky saliva, poor genital development; (2) infancy and early childhood: activity gradually increases, muscle tone gradually improves, but there are still feeding difficulties, the child’s growth is backward, gross motor, language poor development, about 3/4 of patients present depigmented features associated with family background; (3) childhood: irresistible polyphagia leading to obesity, excessive centripetal obesity is the most striking feature, combined with short stature, presenting a stumpy appearance, often with behavioral problems, varying degrees of mild mental retardation, mostly mild, abnormal cognitive function, individual irritable thirst and polyuria. Typical facial features are narrowing of the diameter between the foreheads, almond eyes, strabismus, plump cheeks, reduced imitative movements due to hypotonia, and often sticky saliva at the corners of the mouth, and the patient is relatively insensitive to painful stimuli (including pain caused by taking blood samples; (5) adolescence: most present heavy obesity, with emotional instability, dull motor skills, poor recognition and insatiable hunger as its distinctive features. There are also peculiar behaviors, learning difficulties, poor logical thinking ability and drowsiness; hypogonadism and hypofunction are seen, cryptorchidism and small penis in males, lack of labia and clitoris in females and delayed or incomplete development of secondary sexual characteristics. Due to excessive caloric intake, diabetes, hypertension, and fatty liver occur at or just after puberty.
Due to the multifaceted problems of patients with PWS, a single intervention is not reasonable and a series of treatment plans, including dietary intervention, exercise therapy, and medication, need to be developed for different individuals. In hypogonadism, sex hormone replacement therapy can improve sexual characteristics and promote psychological maturation, especially in male patients, and can promote the development of male secondary sexual characteristics. Growth hormone replacement therapy is accepted and recognized worldwide and has been widely used because of its high safety profile. Surgery is also an option for children with very severe obesity.