ORIGINAL RESEARCH ARTICLEPurpose: Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS. Methods:In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.Results: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations. Conclusion:Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.

IntroductionThe aims of this study were to evaluate levels of health-related quality of life (HRQOL) and the presence of anxiety and depressive symptoms in children with primary immunodeficiency disease (PID) in Serbia.Materials and methodsSelf- and parent-rated data from 25 children with PID were available. As controls, data from 50 children with juvenile idiopathic arthritis (JIA) and 89 healthy children were included. The Pediatric Quality of Life Inventory was used for HRQOL assessments. Anxiety symptoms were identified using the Screen for Child Anxiety-Related Emotional Disorders questionnaire, while depressive symptoms were identified using the Mood and Feeling Questionnaire.ResultsChildren with PID had significantly lower Pediatric Quality of Life Inventory total scores compared to children with JIA and healthy children as child-rated (P=0.02) and parent-rated (P<0.001). Specifically, they had significantly lowered emotional functioning compared to children with JIA, and social functioning compared to both children with JIA and healthy children. School functioning was significantly lower among children with PID (parent-rated only). By parent-rated responses, six (24%) out of 25 children with PID had significant anxiety symptoms, while five (20%) children had significant depressive symptoms, which was statistically higher than among children with JIA and healthy controls (P=0.05).ConclusionHRQOL could be significantly compromised in children with PID, particularly across such psychosocial domains as emotional, social, and school. These children were also found to be at an increased risk for suffering significant anxiety and depressive symptoms.

Liddle syndrome should be considered as a cause of hypertension in children or adolescents particularly with suppressed renin activity. Early diagnosis and appropriately tailored treatment avoid complications of long-term unrecognized or inappropriately managed hypertension.

No abstract

Background Intracardiac myxomas in Carney complex are significant causes of cardiovascular morbidity and mortality through embolic stroke and heart failure. The genetic, clinical and laboratory characteristics of Carney complex-related strokes from atrial myxomas have not been described before. The PRKAR1A gene is mutated in more than 60% of the cases of Carney complex. Methods and Results We studied patients with strokes and cardiac myxomas that were hospitalized in our institution and elsewhere: a total of 7 patients with 16 recurrent atrial myxomas and more than 14 episodes of strokes were identified. Neurological deficits were reported; in one patient, an aneurysm developed at the site of a previous stroke. All patients were female, most had presented with Cushing syndrome, and all had additional tumors or other Carney complex manifestations. Other than gender, although there was a trend for patients being overweight and hypertensive, no other risk factors were identified. A total of 5 patients (71%) had a PRKAR1A mutation; all mutations (c418_419delCA, c.340delG/p.Val113fsX15, c.353_365del13/p.Ile118fsX6, c.491_492delTG/p.Val164fsX4, c.177+1G>A) were located in exons 3–5 and introns 2–3, and all led to a non-sense PRKAR1A mRNA. Conclusions Female Carney complex patients appear to be at a high risk for recurrent atrial myxomas that lead to multiple strokes. Early identification of a female patient with Carney complex is of paramount importance for the early diagnosis of atrial myxomas and the prevention of strokes.