Prader-Willi syndrome, also known as Prader-Labhar-Willi syndrome, pleasant puppet syndrome, cryptorchid-dwarf-obesity-hypogonadism syndrome, and hypotonia-hypogonadism-hypogonadism and obesity syndrome. The disorder was first reported by Prader et al. in 1965, and hundreds of cases have been reported to date. There are no racial or gender differences in the onset of the disease, and the incidence in China is unknown. It is expected that 50-100,000 patients will be affected in China, with 1500-4500 new cases per year (estimated at an incidence of 1/12,000 to 1/15,000 abroad). The causes and genetic mechanisms of PWS are very specific and complex, with the majority of cases being de novo mutations, i.e., both parents are normal, and only a very small number are inherited. The majority of cases can be attributed to genetic errors made during the egg (sperm) or embryo formation stage, i.e. more than 10 genes are missed or suppressed on the long arm of chromosome 15. This disorder is a typical example of genomic imprinting of a non-Mendelian genetic phenomenon. Its etiology is caused by microdeletions in the near-central critical region (15qll.2-ql2) of the long arm of chromosome 15, i.e., by deletions in the uniparentaldisomy of chromosome 15 from the maternal side or in a critical fragment on chromosome 15 from the paternal side. A major difference in PWS obesity is an increase in ghrelin levels, which are decreased in other forms of obesity. Ghrelin, a gastric-derived protein, may be at least partially responsible for the excessive appetite in PWS. The present study shows the presence of SNRPN, NDN, MAGEL2, MKRN3 and Cl5orf2 imprinted genes in the 15q11-q13 region, which are present only on the paternal chromosome 15 allele. ssNRPN, located in the central region of the imprint, encodes five snoRNAs and is thought to be closely related to the PWS phenotype and the most reliable diagnostic locus for The majority of PWS can be detected and can be used for prenatal diagnosis. In normal individuals, the CpG island of the maternal 15q11-q13 region of SNRPN is highly methylated, whereas the CpG island of the paternal SNRPN is unmethylated, so that the maternal gene is inactivated while the paternal SNRPN gene is expressed (genetic imprinting). When the paternal-derived 15q11-q13 region SNRPN is absent (or functionally defective), the affected child exhibits the phenotype of PWS. Clinical symptoms and characteristics Clinical symptoms are complex and vary by age, with individual differences in symptoms and severity. Individuals with this disorder have difficulty feeding and grow slowly during the neonatal period, and generally start eating uncontrollably from about 2 years of age, thus leading to continuous weight gain and severe obesity, and need to prevent symptoms such as diabetes, hyperlipidemia, hypertension, and scoliosis due to obesity. The child has normal language skills, but the actual IQ is lower than that of the general population. 1. Newborn and infancy: low fetal movement during pregnancy, low birth weight, hypotonia (soft body), feeding difficulties (not eating, sucking and swallowing difficulties, often requiring nasogastric tube filling), weak crying (no crying), poor limb mobility (not moving), slow growth, lethargy, recurrent respiratory infections, inadequate lung ventilation, pneumonia, sleep apnea, laryngeal tenderness, heart problems (oval foramen not closed). Malnutrition in infancy is a prominent manifestation in children with PWS in China. 2. Special appearance (with or without): narrow face, narrow convex forehead, long cranium, monocular eyelids, almond eyes, strabismus, narrow nasal bridge, thin upper lip, drooping corners of the mouth, small mouth, short stature, white skin, lighter light brown hair color, small jaw deformity, ear deformity, small hands and feet, narrow hands with straight ulnar margins, and cryptorchidism. 3. Appetite problems: Due to the dysfunction of the inferior optic thalamus, patients have no sense of satiety and develop hyperphagia from the age of 1 to 6 years and cannot control themselves. Excessive obesity will lead to various complications: metabolic disorders, diabetes, hypertension, coronary heart disease, stroke, non-alcoholic fatty liver, sleep disorders, sleep apnea (drowsiness/snoring), respiratory obstruction, etc. There is a risk of sudden death. Excessive ingestion may lead to severe gastrointestinal perforation. 4. Motor development: Motor development is delayed, e.g., head lifting at 8 months, sitting at 1 year, walking at 2 years, and motor development in school-age children is one to two years later compared to their peers. Although muscle tone improves with age, deficits in muscle strength, coordination, and balance persist. 5. Intelligence/language: Mild to moderate intellectual disability with IQ ranging from about 40 to 105, with an average of 70, and a small number showing severe intellectual disability or normal intelligence. Delayed language development (e.g., not speaking until age 3): defective prosody, poor speech intelligibility, repetitive language. 6. Learning problems: Learning difficulties are caused by low intelligence, high level abstract thinking, mathematical computation, systematic and sequential integration, and poor auditory messaging skills, resulting in poor life skills, problem solving, and social skills later in life. However, memory, reading, especially visual cognition, spatial-conceptual organization ability is better (such as good at puzzles); language comprehension is okay but superficial, language expression ability is good, learning style to demonstrate the action with oral explanation, can enhance the learning effect. 7. Emotional behavior problems: poor frustration tolerance, emotional instability, impulsiveness, irritability, skin picking (self-damaging), programmed behavior, stubbornness, uncooperative, argumentative, oppositional, defiant, stealing and lying (food-related), hiding food, possessive, interpersonal withdrawal, self-centeredness, self-talk, loud talking, pacing back and forth, hyperactivity, homoeroticism, obsessive-compulsive disorder, depression (increasingly severe after adolescence), violent behavior, inattention. The following are some of the most common symptoms of hypogonadism 8. gonadal dysgenesis: gonadal hormones are usually insufficient, young boys have undescended testicles (single or bilateral cryptorchidism requires surgery), short penis; girls have labia minora and clitoris, secondary sexual characteristics are not obvious, puberty is mostly delayed and incomplete, there are no reports of childbirth. 9. Eye problems: Convergent strabismus/internal strabismus, myopia, hyperopia, astigmatism, upward slanting of the outer corners of the eyes, blue sclera, Brush-Field (gray) spots in the iris, cataracts. 10. Dental problems: Most of the patients have oral problems such as tooth decay, tooth loss, tooth alignment abnormalities due to too soft tooth enamel, sticky saliva, teeth grinding, regurgitation, etc. 11. abnormalities in thermoregulation: unstable body temperature in infancy often with persistent fever, altered temperature sensitivity in older children and adults. 12. Skeletal system: high incidence of scoliosis (about 30% before age 10, about 80% after age 10, and may worsen with growth hormone treatment) or hunchback, osteoporosis (prone to fracture), hip dysplasia (prone to dislocation), foot exostosis, abnormal balance of lower limbs. Radiographs and regular review are required. 13. Other: high pain threshold and relative insensitivity to painful stimuli. Absence of vomiting. Gastroparesis: delayed gastric emptying phenomenon due to gastric hypokinesis. Hypothyroidism. Hypoadrenalism. Pruritus of the skin. Post-anesthetic resuscitation (PWS patients may have abnormal reactions to regular doses of drugs and anesthetics requiring close monitoring). Nocturnal enuresis. Occasional convulsions, seizures or psychiatric disorders. In addition: in 2001, the British literature reported a mortality rate of up to 3% for PWS. I. Clinical score diagnosis II. Molecular genetic diagnosis III. Differential diagnosis For cases not found positive by methylation analysis such as MS-MLPA, the presence of other PW-like phenotypes needs to be clarified by combining the results of chromosome G-band karyotype analysis levelarrayCGH and other analyses. Treatment 1.Eating behavior and nutritional management 2.Gonadal dysplasia and pubertal development management 3.Growth hormone treatment 4.Other endocrine problems management 5.Genetic counseling 6.Follow-up
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