Prader-Willi syndrome (PWS) was the first human disease to be identified as a result of defective genomic imprinting. Genomic imprinting is a non-Mendelian mode of inheritance that exists only in mammals and refers to the differential expression of alleles of different parental origins in the somatic cells of the progeny after epigenetic modification of certain genes in the gametes or zygotes. The small nuclear ribonucleoprotein polypeptide N (SNRPN) gene at chromosome 15q11.2-13 is an important gene in this syndrome, and the CpG island of the maternal SNRPN is highly methylated in normal individuals, whereas that of the paternal SNRPN is not methylated. methylated, so that only the gene from the father is expressed, while the gene of maternal origin is inactivated. The syndrome was first described in 1887 and was found to be due to loss of the imprinted gene at position 15q11.2-13 of paternal origin in 1980. There is no significant difference in incidence between men and women. It occurs in all races with some variation in prevalence; in the United States it ranges from 1/16,000 to 1/25,000. Seventy percent of PWS is due to a deletion of the paternally derived 15q11.2-13 fragment, 28% is due to maternal uniparental diploidism, and less than 1% of children are due to a mutation in the center of the imprinting. Among the existing methods for diagnosing PWS, fluorescence in situ hybridization is the most technically and instrumentally demanding, takes a long time, and can only diagnose PWS due to deletion of a gene fragment in 70% of the children. In addition children with maternal uniparental diploidy and mutations in the gene imprinting center causing PWS cannot be diagnosed by the fluorescence in situ hybridization method. The method reported herein utilizes two methylation-specific nucleic acid endonucleases, McrBC and Hpa II, to digest the DNA template prior to PCR amplification of the DNA.McrBC specifically digests methylated cytosine, the normal maternally derived sequence; in children with PWS, the SNRPN sequence is not amplified due to the absence of the paternally derived sequence, which is digested by the enzyme.Hpa II can digest CpG sequences that are not methylated, i.e., normal parent-derived sequences; in children with PWS, since the parent-derived sequences are missing, Hpa II digestion has no effect on the patient’s DNA, and SNRPN sequences can be amplified. This method, together with the methylation-specific polymerase chain reaction method after sodium metabisulfite treatment, can detect 99% of children with PWS, including PWS due to both deletion of gene fragments and maternal uniparental diploidy.This method is simple and easy to use, with low instrumentation requirements, and is suitable for rapid clinical diagnosis. Typical PWS is characterized by decreased fetal movement during pregnancy, severe hypotonia in the neonatal period, feeding difficulties, scrotal hypoplasia or cryptorchidism. Subsequently, the hypotonia gradually improves, and from about 1 to 6 years of age, the child’s appetite suddenly increases, which is not easy to control, and gradually develops into obesity; the child’s motor and intellectual development can be found to be backward in this period. Adolescents show short stature (relative to genetic height), central hypogonadism, and may have behavioral problems such as temper tantrums, stealing food, and obsessive-compulsive behaviors.Gunay-Aygun et al.[5] reported that >97% of children with PWS had neonatal hypotonia and developmental lag, and >93% had feeding difficulties in infancy, hyperphagia, weight gain, and sexual developmental lag at the age of 1 year. The results are summarized in the following table. However, five cases of PWS without neonatal hypotonia and feeding difficulties have been reported in China. During the diagnostic process of PWS, the receiving physician is prone to suspect the disease when the child presents with increased appetite and weight gain after 1 year of age. In neonates and infants, children with PWS present with central hypotonia and feeding difficulties, which need to be differentiated from other conditions that cause floppy children, such as cerebral hypoplasia (floppy palsy) and congenital myopathies. In contrast to congenital myopathies, children with PWS have severe central hypotonia but generally breathe normally and do not require mechanical respiratory support. The first 2 cases in this article were misdiagnosed as cerebral palsy in the neonatal period. Currently, most of the children with PWS reported in China are after the onset of obesity symptoms. Due to the simplicity of the methylation analysis method, if this disease is suspected in the neonatal period, it can be quickly diagnosed by this method, so that the children can be effectively treated in a timely manner. Recombinant human growth hormone has been used in the treatment of PWS for more than 10 years, and was formally approved for use by the U.S. Food and Drug Administration in 2000. Large numbers of children treated at several clinical centers have shown that recombinant human growth hormone increases the linear rate of height growth and significantly improves the final height of patients. Early treatment has been shown to be more effective in improving height, as well as increasing the rate of carbohydrate metabolism, reducing fat accumulation, and promoting motor and cognitive development. However, during the treatment with recombinant human growth hormone, the respiratory system of the children should be closely observed, and parents should be instructed to pay attention to the children’s sleep at night, and observe whether there is snoring and apnea, so as to prevent death from asphyxiation due to respiratory obstruction, and to carry out tonsil and proliferative adenoidectomy if necessary. The risk of recurrence of PWS due to gene deletion and maternal uniparental diploidy is very low at 1%, whereas the risk of recurrence of PWS due to mutations in the center of imprinting is high at 50%. For better genetic counseling and prenatal diagnosis, patients need further analysis of the molecular mechanisms of the disease.