Evaluation of an In-House Genetic Testing Method for Confirming Prader-Willi and Angelman Syndromes in Sri Lanka.

BACKGROUND: Prader-Willi syndrome (PWS, MIM 176,270) and Angelman syndrome (AS, MIM 105,830) are caused by imprinting defects of chromosome 15q11-13, with loss of maternal gene expression causing AS and paternal gene expression causing PWS. The diagnosis, once established in most cases by using a methylation-specific PCR test, enables appropriate therapeutic interventions and avoids the need for further investigations. Genetic testing for PWS/AS is limited in Sri Lanka (and in other low- and middle-income countries), mainly because parents are unable to pay for testing as these are not funded by the health service. METHODS: Ninety cases (46 female) with clinical features suggesting PWS (n = 37) and AS (n = 53), referred by a pediatric endocrinologist and a pediatric neurologist, were recruited. Clinical information and blood samples were obtained following informed consent. DNA was extracted and methylation-specific PCR (MS-PCR) was performed following bisulfite modification of DNA by using an in-house method and a kit. Results were validated using known positive controls. Parent-child trio DNA samples were used in cases with confirmed PWS and AS to determine if the disease was due to a deletion or uniparental disomy. The cost of the MS-PCR testing of the two modification methods and the microsatellite analysis was determined. RESULTS: Among the suspected PWS cases, 19/37 were positive, while 5/53 of the suspected AS cases were positive. The lower identification rate of AS is probably related to the overlap of clinical features of this condition with other disorders. The kit-based modification method was more reliable, less time-consuming, and cost-effective in our laboratory. CONCLUSIONS: The kit-based modification followed by MS-PCR described in this study enables more affordable genetic testing of suspected PWS/AS cases, and this is likely to improve patient care by targeting appropriate therapy for the affected cases. Parental genetic counselling is made possible regarding the low recurrence risk, especially where a deletion or uniparental disomy is confirmed. In MS-PCR, negative cases with a strong clinical suspicion of AS, UBE3A mutation testing is required. In addition, imprinting center mutation/deletion testing may also be needed in strongly clinically suspected, MS-PCR negative PWS and AS cases.

Congenital Central Hypoventilation Syndrome and Disorders of Control of Ventilation.

Congenital disorders of ventilatory control typically manifest as central apneas, periodic breathing, and hypoventilation in the neonatal period, but some may present at a later age. Obstructive apneas may be the initial presentation, and some may have associated autonomic nervous system dysfunction. Individuals with these disorders can have absent or impaired ventilatory and arousal responses to hypoxemia and hypercapnia. This article discusses the presentation, pathophysiology, evaluation, and management of congenital central hypoventilation syndrome, rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome, Prader-Willi syndrome, and myelomeningocele.

Diagnosis of Two Unrelated Syndromes of Prader-Willi and Calpainopathy: Insight from Trio Whole Genome Analysis and Isodisomy Mapping.

PURPOSE: An investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM#176270) using joint whole genome sequencing (WGS). METHODS: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. RESULTS: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15, expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2-15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. CONCLUSION: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM#253600) in the same patient. This report highlights the utility of joint analysis and the need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotypes.

Genotype-phenotype characteristics of 57 patients with Prader-Willi syndrome: a single-center experience from Turkey.

OBJECTIVES: Prader-Willi syndrome (PWS) is a rare and complex genetic disorder caused by the loss of expression of the paternal copy of the imprinted genes on chromosome 15q11-q13. A variety of findings have been reported on the phenotypic differences between the genetic subtypes of PWS. This article compares the clinical findings of 57 PWS patients by genetic subtype and explores possible associations in this context. METHODS: Methylation­specific multiplex ligation-dependent probe amplification and single nucleotide polymorphism microarrays were used to diagnose deletion and uniparental disomy (UPD). For phenotype-genotype correlation, clinical data were collected and genetic subgroups were compared statistically, and P  < 0.05 was considered to indicate statistical significance. RESULTS: These 57 patients consisted of 15 type I deletions, 20 type II deletions, six atypic deletions, 11 heterodisomy UPD, four isodisomy UPD, and one translocation-type PWS. All patients had hypotonia, poor neonatal sucking, and feeding difficulties during infancy. Other PWS-related clinical findings, such as speech articulation problems (85.9%), sleep apnea (77.2%), normal birth length (71.9%), small hands/feet (71.9%), childhood polyphagia (57.9%), clinodactyly (56.1%), thick viscous saliva (54.4%), and behavioral problems (50.9%) were observed at varying rates with no statistical difference between genetic subtypes in general. CONCLUSION: This study highlights the phenotype-genotype associations on PWS from a cohort of Turkish pediatric patients as a single-center experience.

Prader-Willi Syndrome: The More We Know, the Less We Know.

Prader-Willi syndrome (PWS) is a complex genetic neurodevelopmental disorder with multisystem impact and a unique behavior profile that evolves over the life span. Beyond the primary care needs of all children and adults, the unique medical concerns and management needs of those with PWS are best served in a multidisciplinary academic center. Our PWS center has provided care for individuals with PWS and their families since 1981. Our growth hormone studies contributed to growth hormone supplementation becoming standard of care in this country. Here, in collaboration with the primary care provider, early childhood intervention programs, schools and local parent organizations, solid, patient-centered care for affected individuals and their families can be provided across the life-span. The purpose of this article is to provide a brief overview of PWS and the attendant medical and behavior management challenges attendant to the disorder.

NanoImprint: A DNA methylation tool for clinical interpretation and diagnosis of common imprinting disorders using nanopore long-read sequencing.

INTRODUCTION: Long-read whole genome sequencing like Oxford Nanopore Technology, is increasingly being introduced in clinical settings. With its ability to simultaneously call sequence variation and DNA modifications including 5-methylcytosine, nanopore is a promising technology to improve diagnostics of imprinting disorders. METHODS: Currently, no tools to analyze DNA methylation patterns at known clinically relevant imprinted regions are available. Here we present NanoImprint, which generates an easily interpretable report, based on long-read nanopore sequencing, to use for identifying clinical relevant abnormalities in methylation levels at 14 imprinted regions and diagnosis of common imprinting disorders. RESULTS AND CONCLUSION: NanoImprint outputs a summarizing table and visualization plots displays methylation frequency (%) and chromosomal positions for all regions, with phased data color-coded for the two alleles. We demonstrate the utility of NanoImprint using three imprinting disorder samples from patients with Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS) and Prader-Willi syndrome (PWS). NanoImprint script is available from https://github.com/carolinehey/NanoImprint.

[The importance of early recognition of Prader-Willi syndrome]. / Het Prader-Willi-syndroom.

Due to its rare nature and subtle dysmorphisms, Prader-Willi syndrome can be challenging to recognize and diagnose in the neonatal period. Feeding difficulties and hypotonia ('floppy infant') are the most striking characteristics. Prader-Willi syndrome requires specific follow-up and treatment, emphasizing the importance of early recognition.We encountered an infant of three months old with severe hypotonia. The hypotonia ameliorated spontaneously over time, although feeding per nasogastric tube was necessary. There were no apparent dysmorphisms. Extensive genetic investigations showed a maternal uniparental disomy of chromosome 15, fitting with Prader-Willi syndrome explaining all symptoms. After excluding contraindications, treatment with growth hormone therapy was started. Parents were educated regarding medical emergencies specific for Prader-Willi syndrome ('medical alerts'). Although Prader-Willi syndrome is rare, it should always be considered in cases of neonatal hypotonia. Early recognition is paramount as specific recommendations and treatment are warranted.

Establishing a Standardized DNA Extraction Method Using NaCl from Oral Mucosa Cells for Its Application in Imprinting Diseases Such as Prader-Willi and Angelman Syndromes: A Preliminary Investigation.

BACKGROUND: Diagnosing imprinting defects in neonates and young children presents challenges, often necessitating molecular analysis for a conclusive diagnosis. The isolation of genetic material from oral swabs becomes crucial, especially in settings where blood sample collection is impractical or for vulnerable populations like newborns, who possess limited blood volumes and are often too fragile for invasive procedures. Oral swab samples emerge as an excellent source of DNA, effectively overcoming obstacles associated with rare diseases. METHODS: In our study, we specifically addressed the determination of the quality and quantity of DNA extracted from oral swab samples using NaCl procedures. RESULTS: We compared these results with extractions performed using a commercial kit. Subsequently, the obtained material underwent MS-HRM analysis for loci associated with imprinting diseases such as Prader-Willi and Angelman syndromes. CONCLUSIONS: Our study emphasizes the significance of oral swab samples as a reliable source for obtaining DNA for MS-HRM analysis. NaCl extraction stands out as a practical and cost-effective method for genetic studies, contributing to a molecular diagnosis that proves particularly beneficial for patients facing delays in characterization, ultimately influencing their treatment.

Specificity of Early Childhood Hyperphagia Profiles in Neurogenetic Conditions.

Hyperphagia is highly penetrant in Prader-Willi syndrome (PWS) and has increasingly been reported in other neurogenetic conditions (NGC). The Hyperphagia Questionnaire (HQ) was completed by caregivers of 4-8-year-olds with PWS (n = 17), Angelman syndrome (AS; n = 22), Williams syndrome (WS; n = 25), or low-risk controls (LRC; n = 35). All NGC groups were significantly elevated in HQ Total and Behavior scores compared to LRC. Only AS and WS were significantly elevated in the Drive domain, and only PWS in the Severity domain. After controlling for externalizing behavior, HQ Total scores were higher for PWS relative to other groups. Hyperphagic symptoms may not differentiate PWS from other NGCs in early childhood. However, hyperphagic phenotypes may be most severe in PWS. Further investigation of these profiles may inform etiology and syndrome-specific treatments.

Laryngeal clefts in Prader-Willi syndrome: Feeding difficulties and aspiration not always caused by hypotonia.

Feeding difficulties, aspiration, and failure to thrive in infancy are commonly seen in patients with Prader-Willi Syndrome (PWS) and attributed to hypotonia. Patients with PWS and laryngeal clefts were identified by review of medical records at three tertiary care children's hospitals between 2017 and 2022. We present three patients with PWS with feeding difficulties who were also found to have laryngeal clefts which likely contributed to their feeding difficulties. Additional factors such as airway anomalies should be considered in patients with PWS, especially when swallowing dysfunction, dysphagia, or abnormal swallow evaluations are present.

Orthopedic manifestations in children with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a rare genetic disease often associated with bone problems, mainly scoliosis and hip dysplasia (HD). This study aimed to analyze the clinical characteristics of orthopedic deformities in patients with PWS. METHODS: A retrospective study was conducted on 175 patients up to March 2023. The Cobb angle(CA) of the spine, the alpha angle of the hip joint, and the acetabular index (AI) were measured. This study aimed to evaluate the relationship between demographic parameters and bone deformities. RESULTS: Scoliosis was found in 66 patients (43.7%), including 52 (78.8%) with mild scoliosis, 10 (15.2%) with moderate scoliosis, and 4 (6.1%) with severe scoliosis. Only seven patients received orthopedic treatment (10.6%). The median age of scoliosis was 4.5 years old, and the prevalence of scoliosis increased rapidly at the age of 5 years and adolescence. The mean CA in this study increased gradually with age. HD was found in 47 patients (38.2%), and 6 patients received orthopedic treatment (12.7%). The median age at HD was 1.8 years old. The mean AI of the study population decreased with age. The prevalence of HD treated with recombinant human growth hormone (rhGH) was low. No significant differences were observed in sex, genotype, body mass index (BMI), obesity rate, or onset of scoliosis and HD. CONCLUSION: The prevalence of scoliosis and HD was higher in patients with PWS. The onset age and developmental trends of the different skeletal malformations were different. Early diagnosis and treatment are important for the prognosis and treatment of orthopedic diseases in patients with PWS.

The Multiple Odysseys in Research and Clinical Care for Neurogenetic Conditions.

Neurogenetic conditions (NGC; e.g., fragile X, Angelman, Prader-Willi syndromes) represent the cause for intellectual or developmental disabilities in up to 60% of cases. With expanded diagnostic options and an increasing focus on the development of gene therapies comes the potential of improved quality of life for individuals with NGCs and their families. However, these emerging initiatives also bring new challenges and considerations for NGC researchers and clinicians, including considerations for supporting caregivers and assuring outcome measures for clinical trials adequately reflect the lived experiences of people with NGCs. This paper summarizes the advances and current and future challenges of research and clinical service provision for people with NGCs and their caregivers.

Genotype-phenotype correlation in Prader-Willi syndrome: A large-sample analysis in China.

The genotype-phenotype relationship in PWS patients is important for a better understanding of the clinical phenotype and clinical characteristics of different genotypes of PWS in children. We aimed to explore the influence of specific gene changes on the clinical symptoms of PWS and the value of early screening and early intervention of the condition. All data in this study were extracted from the database of the XiaoPang Weili Rare Disease Care Center. The collected information included basic demographics, maternal pregnancy information, endocrine abnormalities, growth and development abnormalities, and other clinical phenotypes. The relationships between genotypes and phenotypes in the major categories of PWS were analyzed. A total of 586 PWS cases with confirmed molecular diagnosis and genotyping were included in this study. Among them, 83.8% belonged to the deletion type, 10.9% the uniparental disomy (UPD) type, and 5.3% the imprinting defect (ID) type. Age-wide comparison among the three groups: The rate of hypopigmentation in the deletion group was higher than that in the UPD group (88.8% vs. 60.9%; p < 0.05); A total of 62 patients (14.2%) had epilepsy; and no statistical significance was found among the three groups (p = 0.110). Age-wide comparison between the deletion and non-deletion types: the rate of skin hypopigmentation and epilepsy in the deletion group was significantly higher than that in the non-deletion group (88.8% vs. 68.4%, p < 0.001; 15.9% vs. 7.6%, p = 0.040). The intergroup comparison for the >2-year age group: there were significant intergroup differences in the language development delay among the three groups (p < 0.001). The incidence of delayed language development was the highest in the deletion group, followed by the UPD group, and the lowest in the ID group. The rates of obesity and hyperphagia in the deletion group were also higher than those in the non-deletion group (71.1% vs. 58.9%, p = 0.041; 75.7% vs. 62.0%, p = 0.016). There are significant differences in the rates of skin hypopigmentation and language developmental delay among the deletion, UPD, and ID genotypes. The patients with deletion type had significantly higher rates of lighter skin color, obesity, hyperphagia, language developmental delay, and epilepsy. The results of this study will help clinicians better understand the impact of different PWS molecular etiologies on specific phenotypes.

A Comprehensive Review of Syndromic Forms of Obesity: Genetic Etiology, Clinical Features and Molecular Diagnosis.

Syndromic obesity refers to obesity occurring with additional clinical findings, such as intellectual disability/developmental delay, dysmorphic features, and congenital malformations. PURPOSE OF REVIEW: To present a narrative review regarding the genetic etiology, clinical description, and molecular diagnosis of syndromic obesity, which is a rare condition with high phenotypic variability and genetic heterogeneity. The following syndromes are presented in this review: Prader-Willi, Bardet-Biedl, Pseudohypoparathyroidism, Alström, Smith-Magenis, Cohen, Temple, 1p36 deletion, 16p11.2 microdeletion, Kleefstra, SIM1-related, Börjeson-Forssman-Lehmann, WAGRO, Carpenter, MORM, and MYT1L-related syndromes. RECENT FINDINGS: There are three main groups of mechanisms for syndromic obesity: imprinting, transcriptional activity regulation, and cellular cilia function. For molecular diagnostic, methods of genome-wide investigation should be prioritized over sequencing of panels of syndromic obesity genes. In addition, we present novel syndromic conditions that need further delineation, but evidences suggest they have a higher frequency of obesity. The etiology of syndromic obesity tends to be linked to disrupted neurodevelopment (central) and is associated with a diversity of genes and biological pathways. In the genetic investigation of individuals with syndromic obesity, the possibility that the etiology of the syndromic condition is independent of obesity should be considered. The accurate genetic diagnosis impacts medical management, treatment, and prognosis, and allows proper genetic counseling.

Use of the MS-MLPA assay in prenatal diagnosis of Prader-Willi syndrome with mosaic trisomy 15.

OBJECTIVE: We present a prenatal diagnosis strategy of using Methylation-Specific Multiplex Ligation-Dependent Probe Amplification (MS-MLPA) for the detection of maternal uniparental disomy 15/trisomy 15 (UPD(15) mat/T15) mosaicism. CASE REPORT: A 43-year-old woman underwent amniocentesis at 19 weeks of gestation due to a high risk of trisomy 15 (T15) as indicated by non-invasive prenatal testing (NIPT). Cytogenetic analysis revealed a karyotype of 46, XX of cultured amniocytes. Further analysis using copy number variation sequencing (CNV-seq) analysis showed 55 % T15 mosaicism. The second amniocentesis was performed and showed a karyotype of 46, XX and 26 % T15 mosaicism by interphase fluorescence in situ hybridization (FISH). MS-MLPA analysis of uncultured amniocytes showed that the copy number ratio of 15q11-13 ranged from 1.3 to 1.5, and the percentage of methylation was between 70 % and 100 %. MS-MLPA assay of cultured amniocytes showed a copy number ratio of 1 and a methylation percentage of 100 %. Therefore, this fetus was identified to be an UPD(15) mat/T15 mosaicism. The parents decided to terminate the pregnancy. CONCLUSION: MS-MLPA can be used in combination with karyotype and CNV-seq for prenatal diagnosis of NIPT high-risk T15 to avoid missed diagnosis of UPD(15) mat/T15 mosaicism.

Ketonuria in an adult with Prader-Willi syndrome and diabetes mellitus: A case report.

RATIONALE: Prader-Willi syndrome (PWS) is a genetic disorder affecting multiple systems. Approximately one-quarter of PWS patients will develop diabetes. Given the uncontrolled hyperphagia and resultant severe obesity in these patients, their glycemic management poses a significant challenge. CASE REPORT: We present the clinical profile of a male patient diagnosed with both PWS and diabetes. Previous administration of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor Canagliflozin resulted in improved glycemic control and weight management. But at the age of 25, the patient was hospitalized due to worsened glycemic control and the detection of ketonuria. After thorough examination and clinical observation, we discovered that the patient ketonuria was associated with enhanced lipid metabolism related to Canagliflozin. After excluding the risk of SGLT-2 inhibitor-induced euglycemic diabetic ketoacidosis, adjustments of the hypoglycemic regimen, building upon prior treatment, were recommended for the patient. CONCLUSION: It is important to note that among patients with both PWS and diabetes, the utilization of SGLT-2 inhibitors can lead to the emergence of ketonuria due to increased lipolysis. Therefore, any decision to discontinue SGLT-2 inhibitors should undergo thorough evaluation.

Effectiveness of the Kaufman Brief Intelligence Test in people with Prader-Willi syndrome.

BACKGROUND: Evaluating intelligence using conventional tools is very complex in patients with Prader-Willi Syndrome (PWS), as it is time consuming and requires levels of care that are difficult to sustain for this population. Therefore, we explore the ability of a brief test to assess intelligence in these patients. METHODS: This study included individuals with a genetically confirmed diagnosis of PWS, with regular attendance at transdisciplinary treatment in an institution dedicated to the care of rare diseases in Argentina. The Wechsler Intelligence Scale for Children (WISC-IV), the Wechsler Adult Intelligence Scale (WAIS-III) and the Kaufman Brief Intelligence Test (K-BIT) were used. RESULTS: Correlation was obtained between the scales in paediatric and adult populations. Within the paediatric population, no significant differences were identified between the WISC-IV scale (Wechsler for paediatrics) and the K-BIT (56.4 ± 8.6, vs. 53.4 ± 10.1, P = 0.28), with a good agreement between the methods {intraclass correlation 0.79 [95% confidence interval (CI) 0.15-0.95]}. Regarding the adult population, the discrimination of the WAIS-III scale (Wechsler for adults) and the K-BIT of adults (16 years and over) presented an acceptable concordance [0.77 (95% CI -0.09; 0.93)], although also underestimating the results (58.3 ± 7.2 vs. 51.1 ± 11.2, P < 0.0001). CONCLUSIONS: We observed the feasibility and potential usefulness of a brief intelligence test (K-BIT) in patients with PWS with an acceptable agreement with conventional tools.

A 14-year-old male patient with diagnosis of Prader-Willi syndrome in Ethiopia: a case report.

BACKGROUND: Prader-Willi syndrome is a complex multisystem disorder due to the absent expression of paternally active genes in the Prader-Willi syndrome-critical region on chromosome 15 (15q11.2-q13). The main clinical features are hyperphagia (which frequently results in early-onset obesity), hypogonadism, developmental delays, typical behaviors (such as obsessive-compulsive tendencies, tantrums, perseveration, insistence on sameness, and rigidity), and distinctive facial features. In infants, the most prominent findings are hypotonia and feeding difficulties. CASE PRESENTATION: This paper highlights a case of a 14 year old male patient of an Ethiopian ethnicity with diagnosis of Prader-Willi syndrome, which is first report in Ethiopia. He presented with progressive excessive weight gain, insatiable appetite, clinical and laboratory features of hypogonadism, ophthalmological refractory error, and facial features of Prader-Willi syndrome, which was further confirmed by genetic analysis. He is currently on lifestyle intervention, testosterone replacement, and treatment for vitamin D deficiency. CONCLUSION: Prader-Willi syndrome should be considered in a child who presents with progressive weight gain and other typical clinical features such as cognitive impairment, excessive insatiable eating, or hypothalamic hypogonadism. Early lifestyle intervention may help to reduce excessive weight gain. To our knowledge, this is the first case reported in Ethiopia.

Age of diagnosis for children with chromosome 15q syndromes.

OBJECTIVE: The objective of this study was to identify the age of diagnosis for children with one of three neurogenetic conditions resulting from changes in chromosome 15 (Angelman syndrome [AS], Prader-Willi syndrome [PWS], and duplication 15q syndrome [Dup15q]). METHODS: Data about the diagnostic process for each condition were contributed by the advocacy organizations. Median and interquartile ranges were calculated for each condition by molecular subtype and year. Comparison tests were run to explore group differences. RESULTS: The median age of diagnosis was 1.8 years for both AS and Dup15q. PWS was diagnosed significantly younger at a median age of 1 month. Deletion subtypes for both PWS and AS were diagnosed earlier than nondeletion subtypes, and children with isodicentric duplications in Dup15q were diagnosed earlier than those with interstitial duplications. CONCLUSION: Understanding variability in the age of diagnosis for chromosome 15 disorders is an important step in reducing the diagnostic odyssey and improving access to interventions for these populations. Results from this study provide a baseline by which to evaluate efforts to reduce the age of diagnosis for individuals with these conditions.

Proteome profiling identifies circulating biomarkers associated with hepatic steatosis in subjects with Prader-Willi syndrome.

Introduction: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by loss of expression of paternal chromosome 15q11.2-q13 genes. Individuals with PWS exhibit unique physical, endocrine, and metabolic traits associated with severe obesity. Identifying liver steatosis in PWS is challenging, despite its lower prevalence compared to non-syndromic obesity. Reliable biomarkers are crucial for the early detection and management of this condition associated with the complex metabolic profile and cardiovascular risks in PWS. Methods: Circulating proteome profiling was conducted in 29 individuals with PWS (15 with steatosis, 14 without) using the Olink Target 96 metabolism and cardiometabolic panels. Correlation analysis was performed to identify the association between protein biomarkes and clinical variables, while the gene enrichment analysis was conducted to identify pathways linked to deregulated proteins. Receiver operating characteristic (ROC) curves assessed the discriminatory power of circulating protein while a logistic regression model evaluated the potential of a combination of protein biomarkers. Results: CDH2, CTSO, QDPR, CANT1, ALDH1A1, TYMP, ADGRE, KYAT1, MCFD, SEMA3F, THOP1, TXND5, SSC4D, FBP1, and CES1 exhibited a significant differential expression in liver steatosis, with a progressive increase from grade 1 to grade 3. FBP1, CES1, and QDPR showed predominant liver expression. The logistic regression model, -34.19 + 0.85 * QDPR*QDPR + 0.75 * CANT1*TYMP - 0.46 * THOP1*ALDH1A, achieved an AUC of 0.93 (95% CI: 0.63-0.99), with a sensitivity of 93% and specificity of 80% for detecting steatosis in individuals with PWS. These biomarkers showed strong correlations among themselves and were involved in an interconnected network of 62 nodes, related to seven metabolic pathways. They were also significantly associated with cholesterol, LDL, triglycerides, transaminases, HbA1c, FLI, APRI, and HOMA, and showed a negative correlation with HDL levels. Conclusion: The biomarkers identified in this study offer the potential for improved patient stratification and personalized therapeutic protocols.