Background Congenital heart diseases (CHDs) are abnormalities that present in the heart since birth and are one of the leading causes of infant mortality in the world. CHDs are more common among children with dysmorphic syndromes. The current study aims to estimate the prevalence of many CHDs in different dysmorphic syndromes. Methods This was a retrospective chart review study conducted on all dysmorphic syndrome patients who attended genetic clinics at King Khalid National Guard Hospital in King Abdulaziz Medical City (KAMC), Jeddah, Saudi Arabia from 2005 to 2016. Dysmorphic pediatric patients less than 14 years old who had genetic testing to confirm their diagnosis were included in the study. Patients who did not have any previous echocardiography were excluded. Results A total of 212 individuals (47% males and 53% females) were included. Eighty-five percent of Down syndrome patients had CHDs, and the most common CHD was an atrial septal defect (ASD) (51%). In patients with Turner syndrome, 45% of them had CHDs, and bicuspid aortic valve (BAV) (40%) was the most common defect. In DiGeorge syndrome, 81% of patients had CHDs, and ventricular septal defect (VSD) (41%) was the most common. In Williams syndrome, 83% of patients had CHDs. All patients with Noonan, Edwards, CHARGE (coloboma, heart defects, atresia choanae (also known as choanal atresia), growth retardation, genital abnormalities, and ear abnormalities), and Rubinstein-Taybi syndromes were found to have CHDs. In Patau syndrome and Joubert syndrome, 50% of patients in each had CHDs. Patients with Prader Willi syndrome had normal findings in the echocardiogram. Conclusion The highest prevalence of CHDs was found in Down syndrome. This study has a significant impact on the future of managing and directing the resources to improve the quality of life for syndromic patients. Further studies are needed to confirm these findings and to increase the local data in the field of CHDs in Saudi Arabia among syndromic patients.

(1) Objective: To compare the accuracy of different indexes of adiposity and/or body composition in identifying metabolic syndrome (MetS) in adult patients suffering from Prader‒Willi syndrome (PWS). (2) Study Design: One hundred and twenty PWS patients (69 females and 51 males), aged 29.1 ± 9.4 years, body mass index (BMI) 36.7 ± 9.9, were evaluated. The following indexes were assessed in each subject: body mass index (BMI), fat-free mass index (FFMI), fat mass index (FMI), tri-ponderal mass index (TMI), waist-to-height ratio (WtHR) and the body mass fat index (BMFI), which adjusts the BMI for the percentage of body fat and waist circumference. Thereafter, a threshold value adjusted for age and sex, which could identify MetS, was calculated for each index. (3) Results: A significant correlation was found among all indexes (p < 0.0001 for all). However, when the area under the curve (AUC) was compared, BMFI performed better than FMI (p < 0.05) and BMI better than TMI (p < 0.05), but only in females. (4) Conclusions: Besides small differences, all the indexes taken into consideration seem to have the same ability to identify MetS in adults with PWS. Consequently, the most easily calculated index, i.e., BMI, should be considered as the best choice. The use of thresholds appropriate for sex and age can further improve its accuracy.

Context: Loss-of-function mutations in the imprinted genes MKRN3 and DLK1 cause central precocious puberty (CPP) but whole gene deletions have not been reported. Larger deletions of the chromosome 15q11-13 imprinted locus, including MKRN3, cause Prader-Willi syndrome (PWS). CPP has been reported in PWS but is not common, and the role of MKRN3 in PWS has not been fully elucidated.

Objective: To identify copy number variants in puberty-related, imprinted genes to determine their role in CPP.

Methods: Probands with idiopathic CPP had chromosomal microarray (CMA) and targeted deletion/duplication testing for MKRN3 and DLK1.

Results: Sixteen female probands without MKRN3 or DLK1 variants identified by Sanger sequencing were studied. Whole gene deletions of MKRN3 were identified in 2 subjects (13%): a complete deletion of MKRN3 in Patient A (pubertal onset at 7 years) and a larger deletion involving MAGEL2, MKRN3, and NDN in Patient B (pubertal onset 5.5 years). Both were paternally inherited. Patient B had no typical features of PWS, other than obesity, which was also present in her unaffected family.

Conclusions: We identified 2 cases of whole gene deletions of MKRN3 causing isolated CPP without PWS. This is the first report of complete deletions of MKRN3 in patients with CPP, emphasizing the importance of including copy number variant analysis for MKRN3 mutation testing when a genetic diagnosis is suspected. We speculate that there is a critical region of the PWS locus beyond MKRN3, MAGEL2, and NDN that is responsible for the PWS phenotype.

Chromosome 15 imprinting disorders include Prader-Willi (PWS) and Angelman (AS) syndromes, which are caused by absent expression from the paternal and maternal alleles in the chromosome 15q11. 2-q13 region, respectively. In addition, chromosome 15q duplication caused by the presence of at least one additional maternally derived copy of the 15q11.2-q13 region can lead to seizures, cognitive and behavioral problems. We focus on PWS and AS in the report, and expand the discussion of clinical care and description with genetic testing to include high-resolution studies to more specifically characterize the molecular mechanisms of disease. The importance of early diagnosis with the necessity for accurate molecular characterization through a step-wise algorithm is emphasized in an era of targeted therapeutic interventions. We present a flowchart to aid in ordering specialized genetic testing as several methods are available for patients presenting with features of PWS and/or AS.

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by the loss of paternally expressed genes in an imprinted region of chromosome 15q11.2-q13. We generated a human-induced pluripotent stem cell line, designated KSCBi009-A, from peripheral blood mononuclear cells of a 13-year-old male PWS patient exhibiting deletion of the paternal chromosome 15q11.2-q13 region. The deletion was confirmed via methylation-specific multiplex ligation probe amplification assay (MS-MLPA) of genomic DNA. The hiPSC line expressed pluripotency markers and differentiated into three germ layers. The cell line may serve as a valuable model of an imprinting PWS disorder useful in terms of drug discovery and development.