Humans ; Prader-Willi Syndrome/therapy*

OBJECTIVE: To study the clinical screening and genetic diagnosis of children suspected of Prader-Willi syndrome (PWS), as well as the differences in the scores of clinical diagnostic criteria among the children with a confirmed diagnosis of PWS. METHODS: A total of 94 children suspected of PWS who were admitted from July 2016 to December 2018 were enrolled as subjects. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to confirm the diagnosis. For the children with a confirmed diagnosis of PWS, the scores of clinical diagnostic criteria were determined, and the perinatal characteristics were analyzed. RESULTS: A total of 11 children with PWS were confirmed by MS-MLPA, with a detection rate of 12%, among whom there were 7 boys and 4 girls, with a median age of 3 years and 4 months (range 25 days to 6 years and 8 months) at the time of confirmed diagnosis. Among the 11 children with PWS, only 5 children (45%) met the criteria for clinical diagnosis. The main perinatal characteristics of the children with PWS were decreased fetal movement (9 cases, 82%), cesarean section birth (11 cases, 100%), hypotonia (11 cases, 100%), feeding difficulties (11 cases, 100%), and weak crying (11 cases, 100%). CONCLUSIONS Gene testing should be performed as early as possible for children suspected of PWS by clinical screening. PWS may be missed if only based on the scores of clinical diagnostic criteria.
Cesarean Section ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Methylation ; Muscle Hypotonia ; Prader-Willi Syndrome ; Pregnancy

OBJECTIVE: To explore the genetic basis for a fetus featuring growth restriction and validate the effectiveness of a novel noninvasive prenatal testing (NIPT) technique for the detection of chromosomal microdeletions. METHODS: Next-generation sequencing(NGS) and fluorescence in situ hybridization(FISH) were used to analyze the DNA of the fetus. Conventional G-banding was used to analyze the karyotypes of the fetus and its parents. High-throughput sequencing was used to analyze free fetal DNA. RESULTS: NGS analysis has revealed a 4.88 Mb deletion at 15q11.2-q13.1 region in the fetus, which has a 99% overlap with the critical region of Prader-Willi syndrome (Type 2) and Angelman syndrome (Type 2) and encompassed critical genes including SNRPN and UBE3A. NIPT also revealed a 4.6 Mb deletion at 15q12, which was consistent with the results of fetal cord blood and amniotic DNA testing. FISH assay has confirmed the result of NGS. By karyotying, all subjects showed a normal karyotypes at a level of 320~400 bands. CONCLUSION It is quite necessary to carry out genetic testing on fetuses showing growth restriction. NIPT for fetal chromosomal microdeletions/microduplication syndromes is highly accurate for the diagnosis of Prader-Willi/Angelman syndrome.
Angelman Syndrome ; Chromosome Banding ; Chromosomes, Human, Pair 15 ; Female ; Fetus ; Humans ; In Situ Hybridization, Fluorescence ; Prader-Willi Syndrome ; Pregnancy

BACKGROUND: To validate the clinical application of chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic test and to determine the impact of CMA results on patient clinical management, we conducted a multicenter prospective study in Korean patients diagnosed as having developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA). METHODS: We performed both CMA and G-banding cytogenetics as the first-tier tests in 617 patients. To determine whether the CMA results directly influenced treatment recommendations, the referring clinicians were asked to complete a 39-item questionnaire for each patient separately after receiving the CMA results. RESULTS: A total of 122 patients (19.8%) had abnormal CMA results, with either pathogenic variants (N=65) or variants of possible significance (VPS, N=57). Thirty-five well-known diseases were detected: 16p11.2 microdeletion syndrome was the most common, followed by Prader-Willi syndrome, 15q11-q13 duplication, Down syndrome, and Duchenne muscular dystrophy. Variants of unknown significance (VUS) were discovered in 51 patients (8.3%). VUS of genes putatively associated with developmental disorders were found in five patients: IMMP2L deletion, PTCH1 duplication, and ATRNL1 deletion. CMA results influenced clinical management, such as imaging studies, specialist referral, and laboratory testing in 71.4% of patients overall, and in 86.0%, 83.3%, 75.0%, and 67.3% of patients with VPS, pathogenic variants, VUS, and benign variants, respectively. CONCLUSIONS: Clinical application of CMA as a first-tier test improves diagnostic yields and the quality of clinical management in patients with DD/ID, ASD, and MCA.
Autism Spectrum Disorder ; Autistic Disorder ; Cytogenetics ; Diagnostic Tests, Routine ; Down Syndrome ; Humans ; Intellectual Disability ; Korea ; Microarray Analysis ; Muscular Dystrophy, Duchenne ; Prader-Willi Syndrome ; Prospective Studies ; Referral and Consultation ; Specialization

Prader-Willi syndrome (PWS) is a quite rare multi-systemic genetic disorder strongly associated with psychiatric illness in adults, especially psychosis. This report presents a 16-year-old female with PWS and symptoms of brief psychotic disorder with a complete resolution of symptoms under aripiprazole medication. However, an exacerbation occurred after aripiprazole reduction. Apart from a weight gain of about 2 kg over the course of two years, no adverse effects could be found. This first report on the use of aripiprazole in a subject with PWS and psychosis suggests that aripiprazole might be a promising treatment approach in this distinct group of patients.
Adolescent ; Adult ; Aripiprazole* ; Female* ; Humans ; Prader-Willi Syndrome* ; Psychotic Disorders* ; Weight Gain

PURPOSE: Floppy infants or congenital hypotonia indicates decreased muscle tone in infants secondary to abnormalities of the central or the peripheral nervous system, or both. Previous literature classified its causes as those attributable to a central vs. peripheral origin; however, recent studies have introduced a newer classification describing a combined origin. We invenstigated floppy infants by applying the new etiological classification and reviewed the most common etiologies based on the age of presentation. We additionally reviewed the clinical characteristics, diagnoses, and the developmental outcomes in these infants. METHODS: We retrospectively reviewed the electronic medical charts and recruited 116 infants diagnosed with floppy infant syndrome between January 2005 and December 2016 at Severance Children's Hospital. Among these infants, 66 with a confirmed diagnosis were reviewed for the etiological classification. Information regarding developmental outcomes was obtained via phone interviews with the infants' families. RESULTS: Based on the new etiological classification, among 69 infants with a confirmed diagnosis, in 40 (34.5%) this syndrome was of central origin, in 19 (16.4%) of peripheral origin, and in 10 (8.6%) of combined origin. Prader-Willi syndrome, myotonic dystrophy, and spinal muscular atrophy were the most common disorders observed and combined hypotonia showed the poorest developmental outcome. CONCLUSION: The study states the importance of proper evaluation of etiological diagnosis and optimal intervention for developmental prognosis. The introduction of a new etiological group of combined hypotonia especially emphasizes regular monitoring and timely rehabilitative intervention in patients for the better quality of life in them as well as their caregivers.
Caregivers ; Classification* ; Diagnosis ; Humans ; Infant* ; Muscle Hypotonia ; Muscular Atrophy, Spinal ; Myotonic Dystrophy ; Peripheral Nervous System ; Prader-Willi Syndrome ; Prognosis ; Quality of Life ; Retrospective Studies

OBJECTIVETo screen for genomic copy number variants (CNVs) in a fetus with one sibling affected with Prader-Willi syndrome using single nucleotide polymorphism (SNP) array.

METHODSThe fetus and its parents were subjected to chromosomal karyotyping and SNP array analysis.

RESULTSA 5p15.33 microdeletions was identified in the fetus and its phenotypically normal mother with a size of 344 kb (113 576 to 457 213). The father was normal for both testing. Analysis of literature and CNVs database indicated the above CNV to be variant of unclear significance. The couple decided to continue with the pregnancy and gave birth to a healthy boy at full-term. No abnormalities were found during the follow-up.

CONCLUSIONThis study may provide further data for the phenotype-genotype correlation of 5p15.33 microdeletion, which differs from Cri du Chat syndrome.

Adult ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; genetics ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Male ; Prader-Willi Syndrome ; diagnosis ; embryology ; genetics ; Pregnancy ; Prenatal Diagnosis

This article reports the clinical features and endocrine and metabolic features of 4 children with Prader-Willi syndrome (PWS). All the patients were female and aged 6-12 years at diagnosis. All of them had clinical manifestations of obesity, unusual facies, developmental retardation, and intellectual disability. Genetic detection showed that 2 patients had paternal deletion of the 15q11.2-q13 region, one patient had maternal autodiploid in the 15q11.2-q13 region, and one patient had no abnormality in the 15q11.2-q13 region. All patients had varying degrees of endocrine and metabolic disorders: 2 patients had short stature, among whom one had delayed appearance of secondary sex characteristics and the other one had type 2 diabetes; one patient had insulin resistance and no mammary gland development; one patient had a body height of P-Pand precocious puberty. Patients with PWS have various endocrine disorders, so long-term endocrine follow-up and management is very important.
Child ; Child, Preschool ; Endocrine Glands ; physiopathology ; Female ; Glucose Tolerance Test ; Humans ; Prader-Willi Syndrome ; genetics ; physiopathology

We treated a 4-year-old patient with a genetic disorder, Prader-Willi syndrome, that was accompanied by pulmonary hypertension due to upper airway obstruction. Prader-Willi syndrome is a complex genetic condition characterized by hypotonia, feeding difficulties, poor growth, and delayed development. Hypotonia was the main concern in the anesthetic management of this patient, including the choice of a neuromuscular blocking agent. We report successful induction of anesthesia in this patient with sevoflurane inhalation, remifentanil infusion, and a non-depolarizing muscle relaxant, rocuronium, while following up the status of the neuromuscular block by train-of-four monitoring and reversing the neuromuscular block with sugammadex.
Airway Obstruction ; Anesthesia ; Child* ; Child, Preschool ; Humans ; Hypertension, Pulmonary ; Inhalation ; Muscle Hypotonia ; Neuromuscular Blockade* ; Neuromuscular Monitoring ; Prader-Willi Syndrome*

We treated a 4-year-old patient with a genetic disorder, Prader-Willi syndrome, that was accompanied by pulmonary hypertension due to upper airway obstruction. Prader-Willi syndrome is a complex genetic condition characterized by hypotonia, feeding difficulties, poor growth, and delayed development. Hypotonia was the main concern in the anesthetic management of this patient, including the choice of a neuromuscular blocking agent. We report successful induction of anesthesia in this patient with sevoflurane inhalation, remifentanil infusion, and a non-depolarizing muscle relaxant, rocuronium, while following up the status of the neuromuscular block by train-of-four monitoring and reversing the neuromuscular block with sugammadex.
Airway Obstruction ; Anesthesia ; Child* ; Child, Preschool ; Humans ; Hypertension, Pulmonary ; Inhalation ; Muscle Hypotonia ; Neuromuscular Blockade* ; Neuromuscular Monitoring ; Prader-Willi Syndrome*