Prader-Willi syndrome (PWS) is a complex genetic disorder caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region, known as the Prader Willi critical region. Nutritional clinical manifestations change with age and are described in four different phases. The phases span both extremes of the nutritional spectrum, beginning with an infant with poor sucking reflexes and failure to thrive then progressing to an adolescent who may have hyperphagia and be at risk for obesity. The phenotype is likely due to hypothalamic dysfunction due to genetic changes in the Prader Willi critical region. Researchers are examining the pathological mechanisms that determine the disease course.

OBJECTIVE: The effect of recombinant human growth hormone (rhGH) on sleep-disordered breathing (SDB) in Malaysian children with Prader-Willi syndrome (PWS) is under-investigated. We determined (1) the short- and long-term effects of rhGH and (2) factors associated with worsening SDB in children with PWS receiving rhGH.
METHODS: This retrospective study included children with PWS (with and without rhGH) who had undergone at least 1 polysomnography. Outcomes measured were the presence of SDB before and after starting rhGH and the progress of SDB with and without rhGH. Serial insulin-like growth factor 1 (IGF-1) measurements were recorded.
RESULTS: One-hundred and thirteen polysomnograms were analyzed. The majority (92.3%) of initial polysomnograms showed SDB, with a median (interquartile range) apnea-hypopnea index of 5.0 (2.6, 16.3) events/h. The age for receiving rhGH was a median (IQR) of 1.9 (0.7, 3.4) years. One-third (36.8%) had worsening SDB after initiating rhGH, which was associated with higher IGF-1 levels post-rhGH (P = .007). After a median of 5 years of rhGH, 73.6% maintained or reduced their positive airway pressure settings. Without rhGH, 80% had increased their positive airway pressure settings. Worsening SDB while on rhGH was associated with higher body mass index, lower rhGH dose, higher IGF-1 levels, and non-15q deletion.
CONCLUSIONS: The majority of Malaysian children with PWS had SDB. At initiation of rhGH, one-third of patients had worsening SDB, associated with increased IGF-1 levels. Stabilization of SDB was more frequently seen in those receiving long-term rhGH. Worsening SDB while on rhGH was associated with a higher body mass index, receiving a lower dose of rhGH, higher IGF-1 levels, and non-15q deletion.
BACKGROUND: Tan YT, Azanan MS, Hng SY, et al. Long-term effect of growth hormone on sleep-disordered breathing in Malaysian children with Prader-Willi syndrome: a retrospective study. J Clin Sleep Med. 2024;20(8):1291-1299.

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BACKGROUND: Social communication skills are critical for full participation in social activities in primary life contexts for adolescents and young adults with neurodevelopmental disorders.
METHODS: Two young adults with Prader Willi syndrome participated in an online socialisation programme with elderly and adolescent conversational partners. We used a multiple baseline across conversational partners design for each participant to investigate the effects of textual prompts and constant time delay on the number of initiations and follow-up questions. We evaluated the social validity.
RESULTS: Both participants improved their social communication skills during online socialisation with partners. Participants with Prader Willi syndrome enjoyed participating in this study. Elderly conversational partners reported a slight decrease in loneliness following online socialisation.
CONCLUSIONS: The use of textual prompts and constant time delay may be helpful to promote opportunities for interaction among segments of the population potentially at risk of social isolation during online socialisation.

UNASSIGNED: The prevalence of childhood and adolescent obesity is increasing worldwide as well as in India. Prader--Willi syndrome (PWS) is one of the most common causes of syndromic obesity with varied clinical manifestations across different lifespan. Herewith, we describe clinical and molecular characteristics of eight PWS who were diagnosed in an obesity clinic of tertiary care hospital.
UNASSIGNED: Clinically suspected cases of PWS were screened between January 2014 and January 2022. Detailed history and clinical examination were done to look for typical features of PWS like characteristic facial appearance, short stature, obesity, hyperphagia, delayed puberty or hypogonadism, diabetes mellitus, developmental delay, cognitive dysfunction, learning disabilities or abnormal behavior. All were evaluated, with 75 g oral glucose tolerance tests (GTT), HbA1c, Free T4, TSH, LH, FSH, testosterone, and growth hormone level. Intelligent quotient (IQ) of each patient was assessed by a psychiatrist using Binet-Kamat test. Molecular confirmation of clinically suspected PWS was done by either Methylation-specific polymerase chain reaction (MS-PCR) or Fluorescence in situ Hybridization (FISH) methods.
UNASSIGNED: Based on clinical and molecular characteristics, eight were diagnosed as PWS. Except one, all were male with characteristic facies, mean age of study cohort was 12 years and mean BMI of 44.58. Obesity, short stature, hyperphagia, hypotonia, and mild to moderate mental retardation were noted in entire (100%) PWS study population. All male PWS patients had cryptorchidism, which was bilateral in six patients and unilateral (right undescended testes) in one. Apart from obesity, short stature, other endocrine associations noted were diabetes mellitus in 50% and subclinical hypothyroidism in 37% of PWS. Molecular characteristics of PWS were confirmed by Methylation-specific PCR in seven and by FISH method in one.
UNASSIGNED: Prader-Willi syndrome should be kept in mind in case of childhood or adolescent obesity with short stature, hypotonia, cryptorchidism, and developmental delay or cognitive dysfunction. Judicious use of molecular diagnostic testing should be made in all clinically suspected cases. Early diagnosis and appropriate management of this complex disorder by a multidisciplinary team will improve the quality of life and treatment outcome.

Prader-Willi Syndrome (PWS) is a rare complex genetic disease that is associated with pathological disorders that include endocrine disruption, developmental, neurological, and physical problems as well as intellectual, and behavioral dysfunction. In early stage, PWS is characterized by respiratory distress, hypotonia, and poor sucking ability, causing feeding concern and poor weight gain. Additional features of the disease evolve over time. These include hyperphagia, obesity, developmental, cognitive delay, skin picking, high pain threshold, short stature, growth hormone deficiency, hypogonadism, strabismus, scoliosis, joint laxity, or hip dysplasia. The disease is associated with a shortened life expectancy. There is no cure for PWS, although interventions are available for symptoms management. PWS is caused by genetic defects in chromosome 15q11.2-q13, and categorized into three groups, namely Paternal deletion, Maternal uniparental disomy, and Imprinting defect. PWS is confirmed through genetic testing and DNA-methylation analysis. Studies revealed that at least two key proteins namely MAGEL-2 and NECDIN along with two proteases PCSK1 and PCSK2 are linked to PWS. Herein, we summarize our current understanding and knowledge about the role of these proteins and enzymes in various biological processes associated with PWS. The review also describes how loss and/or impairment of functional activity of these macromolecules can lead to hormonal disbalance by promoting degradation of secretory granules and via inhibition of proteolytic maturation of precursor-proteins. The present review will draw attention of researchers, scientists, and academicians engaged in PWS study and will help to identify potential targets and molecular pathways for PWS intervention and treatment.

UNASSIGNED: Prader Willi Syndrome (PWS) is a genetic disorder caused by the absence of expression of the paternal copies of maternally imprinted gene(s) located at 15q11-q13. While the physical and medical characteristics of PWS, including short stature, hyperphagia and endocrine dysfunction are well-characterized, systematic investigation of the long-recognized psychiatric manifestations has been recent.
UNASSIGNED: Here, we report on the first remote (web-based) assessment of neurobehavioral traits, including psychosis-risk symptoms (Prodromal Questionnaire-Brief Version; PQ-B) and sleep behaviors (Pittsburgh Sleep Quality Index), in a cohort of 128 participants with PWS, of whom 48% had a paternal deletion, 36% uniparental disomy, 2.4% an imprinting mutation and 13% unknown mutation (mean age 19.3 years ± 8.4; 53.9% female). We aimed to identify the most informative variables that contribute to psychosis-risk symptoms. Multiple domains of cognition (accuracy and speed) were also assessed in a subset of PWS participants (n = 39) using the Penn Computerized Neurocognitive Battery (Penn-CNB).
UNASSIGNED: Individuals with PWS reported a range of psychosis-risk symptoms, with over half reporting cognitive disorganization (63.1%) and about one third reporting unusual beliefs (38.6%) and/or suspiciousness (33.3%). Subjectively-reported sleep quality, nap frequency, sleep duration, sleep disturbance, and daytime dysfunction were significant predictors of psychosis-risk symptom frequency and severity (all p\'s < 0.029). Sleep disturbance ratings were the strongest predictors of psychosis-risk symptoms. Regarding cognition, individuals with PWS showed the most prominent deficits in accuracy on measures of social cognition involving faces, namely Face Memory, Age Differentiation and Emotion Recognition, and greatest slowing on measures of Attention and Emotion Recognition. However, there were no significant differences in psychosis-risk symptoms or cognitive performance as a function of PWS genetic subtype.
UNASSIGNED: PWS is associated with a high prevalence of distressing psychosis-risk symptoms, which are associated with sleep disturbance. Findings indicate that self/parent-reported neurobehavioral symptoms and cognition can be assessed remotely in individuals with PWS, which has implications for future large-scale investigations of rare neurogenetic disorders.

The behavior of offspring results from the combined expression of maternal and paternal genes. Genomic imprinting silences some genes in a parent-of-origin specific manner, a process that, among all animals, occurs only in mammals. How genomic imprinting affects the behavior of mammalian offspring, however, remains poorly understood. Here, we studied how the loss of the paternally inherited gene Magel2 in mouse pups affects the emission of separation-induced ultrasonic vocalizations (USV). Using quantitative analysis of more than 1000 USVs, we characterized the rate of vocalizations as well as their spectral features from postnatal days 6-12 (P6-P12), a critical phase of mouse development that covers the peak of vocal behavior in pups. Our analyses show that Magel2 deficient offspring emit separation-induced vocalizations at lower rates and with altered spectral features mainly at P8. We also show that dams display altered behavior towards their own Magel2 deficient offspring at this age. In a test to compare the retrieval of two pups, dams retrieve wildtype control pups first and faster than Magel2 deficient offspring. These results suggest that the loss of Magel2 impairs the expression of separation-induced vocalization in pups as well as maternal behavior at a specific age of postnatal development, both of which support the pups\' growth and development.