Incontinence and psychological symptoms in Phelan-McDermid syndrome

Aims Phelan-McDermid syndrome (PMD) is a congenital syndrome caused by a deletion on chromosome 22q13.3. About 600 cases have been identified worldwide. PMD is characterized by neonatal hypotonia, moderate/severe intellectual impairment, impaired expressive language, and typical dysmorphic features. Psychological symptoms as hyperactivity, attention problems, restlessness, and stereotyped-repetitive behavior were reported. The aim of the study was to assess incontinence and associated psychological problems in PMD. Methods Forty-one individuals with PMD were recruited through a German support group (48.8% male; mean age 13.4 years; range, 4-55 years). Parents or caregivers completed the developmental behavior checklist (DBC), as well as the parental questionnaire: enuresis/urinary incontinence, including six questions on adaptive toileting skills. Results Rates of nocturnal enuresis (NE), daytime urinary incontinence, and fecal incontinence were 86%, 73%, and 79%. Rates were similar in all age groups (children, teens, adults). Constipation was present in 19%. Forty-two percent of the sample had a clinically relevant DBC score, with adults more affected than teens. Persons with NE had significantly higher “anxiety/depression” subscale scores. Toileting skills were more developed in adults than in children. Sixty-eight percent had further physical disabilities. Conclusions Incontinence rates in PMD are high in all age groups. However, persons with PMD can improve their toilet skills. Therefore, the assessment and treatment of incontinence in persons with PMD is recommended. Constipation does not seem to be a major problem in PMD. Due to the high prevalence rates of somatic conditions, an assessment for organic and functional incontinence is recommended

Incontinence in persons with tuberous sclerosis complex

Aims Tuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by a mutation in the TSC1 or TSC2 gene with a broad spectrum of physical and psychological manifestations. The aim of the study was to examine incontinence, psychological problems, and adaptive behavior skills in patients with TSC. Methods Through a worldwide TSC support group, 26 children (4‐17 years) and 15 adults (18‐50 years) with TSC were recruited (38.1% male, mean age 16.4 years). Parents or care‐givers completed the Developmental Behavior Checklist (DBC), the Parental Questionnaire: Enuresis/urinary Incontinence, and the Vineland Adaptive Behavior Scales (3rd edition). Results A total of 60.0% of the participants had nocturnal enuresis (NE), 51.3% daytime urinary incontinence (DUI) and 52.4% fecal incontinence (FI). 65.4% of children and 50.0% of adults had a clinically relevant DBC score. Psychological symptoms were associated with at least one subtype of incontinence. The mean adaptive behavior composite (ABC) score of the patients was 57.2 (SD = 26.1), with 38.1% in the average or below‐average range (IQ >70), 26.2% with a mild, 11.9% with a moderate and 23.8% with a severe/profound intellectual disability. The incontinence rate was significantly higher in the groups with a lower ABC score. Conclusion A substantial proportion of patients with TSC are affected by incontinence and psychological symptoms. Incontinence was higher in persons with lower adaptive skills and those with at least one type of incontinence showed a significantly higher DBC score. As incontinence and psychological problems affect daily functioning and well‐being, assessment, and treatment are recommended

Psychopathologie und elterlicher Stress bei 3- bis 6-jährigen Kindern mit Ausscheidungsstörungen

Objective: Incontinence and functional gastrointestinal disorders are common in young children and are associated with higher rates of psychological symptoms and mental disorders. This article focuses on the mutual association between incontinence and related toilet refusal syndrome, parental stress, and children’s psychopathology especially in young children. Methods: Children’s psychological symptoms, mental disorders, and parental stress levels were assessed in 38 parent-child dyads involving children with incontinence and 42 dyads of typically developing (TD) children. Results: Compared to TD children, patients had higher internalizing and externalizing CBCL scores and higher rates of clinically relevant externalizing problems. However, the rates of clinically relevant internalizing problems and mental disorders did not differ. The parents of children with incontinence reported signifi cantly higher stress levels regarding child-related stress factors (PSI-CD) than did parents of TD children. However, there were no clinically relevant parental stress scores on a group level, which remained below the clinical range (T-value < 60). When simultaneously analyzed, children’s (comorbid) mental disorders but not incontinence had a major impact on parental stress. Conclusions: Despite moderate stress levels, incontinence symptoms, urinary and fecal incontinence are highly prevalent in young children. However, stress among parents of young children was mainly elicited by any (comorbid) mental disorder.Fragestellung: Ausscheidungsstörungen (AS) wie funktionelle Harn- und Stuhlinkontinenz sind sehr häufi ge Störungen im Vorschulalter und sind mit einer erhöhten Prävalenz von psychopathologischen Symptomen und psychischen Störungen bei den betroffenen Kindern assoziiert. Innerhalb der vorliegenden Arbeit wird der wechselseitige Zusammenhang von funktioneller Harn- und Stuhlinkontinenz sowie dem damit in Verbindung stehenden Toilettenverweigerungssyndrom auf die kindliche Psychopathologie und das elterliche Stresserleben speziell bei jungen Kindern untersucht. Methode: Psychopathologische Symptome, psychische Störungen und elterliche Stressbelastung wurden in 38 Eltern-Kind-Dyaden bei Kindern mit vorhandener AS und in 42 Dyaden bei Kindern ohne AS untersucht. Ergebnisse: Kinder mit AS wiesen höhere Werte von internalisierendem und externalisierendem Problemverhalten auf und waren häufi ger von klinisch relevanter externalisierender Symptomatik betroffen. Nichtsdestotrotz war die Prävalenz psychischer Störungen vergleichbar. Eltern von Kindern mit AS berichteten signifi kant höhere kindbezogene Stresslevel. Dennoch zeigte sich auf Gruppenebene kein klinisch bedeutsamer elterlicher Stress und die mittleren Stresslevel lagen unterhalb des Bereichs der klinischen Auffälligkeit (T-Wert < 60). Bei gleichzeitiger Betrachtung des Einfl usses von AS und psychischen Störungen zeigten sich letztere als ausschlaggebend für den elterlichen Stress. Schlussfolgerungen: Trotz moderater Stresslevel konnte eine generell hohe Prävalenz von AS Symptomen bei 3–6-Jährigen aufgezeigt werden. Elterlicher Stress war jedoch bedeutsamer mit einer (komorbiden) psychischen Erkrankung assoziiert

Questioning a South African hypertension threshold of 150 mm Hg – Authors' reply

We are grateful for the opportunity to respond to Schutte and colleagues. We agree with Schutte and colleagues that the systolic blood pressure (SBP) measurements presented in our study could contain error. However, of the potential sources of measurement error they note (whitecoat effects [+2·5 mm Hg], averaging measurements from two different waves [+3·8 mm Hg], and supine measurements [+3–10 mm Hg]), only the white-coat effects potentially applies to our study. Although we average measurements from 2 different years, we assign the resulting SBP to the last year of data. Therefore, any bias would result in SBP measurements that are conservative, rather than inflated by 3.5 mm Hg. SBP in the National Income Dynamics Survey is also measured in a sitting, not supine, position; however, Schutte and colleagues correctly identified our reporting error, and we have requested a formal correction. On balance, any measurement error is likely to be much smaller than Schutte and colleagues assert and would not change our main study conclusions

An Expert Perspective on Phosphate Dysregulation With a Focus on Chronic Hypophosphatemia

Because of their rarity, diseases characterized by chronic hypophosphatemia can be underrecognized and suboptimally managed, resulting in poor clinical outcomes. Moreover, serum phosphate may not be measured routinely in primary care practice. Authors participated in several working sessions to advance the understanding of phosphate homeostasis and the causes, consequences, and clinical implications of chronic hypophosphatemia. Phosphate levels are regulated from birth to adulthood. Dysregulation of phosphate homeostasis can result in hypophosphatemia, which becomes chronic if phosphate levels cannot be normalized. Chronic hypophosphatemia may be underrecognized as serum phosphate measurement is not always part of routine analysis in the primary care setting and results might be misinterpreted, for instance, due to age-specific differences not being accounted for and circadian variations. Clinical consequences of chronic hypophosphatemia involve disordered endocrine regulation, affect multiple organ systems, and vary depending on patient age and the underlying disorder. Signs and symptoms of chronic hypophosphatemic diseases that manifest during childhood or adolescence persist into adulthood if the disease is inadequately managed, resulting in an accumulation of clinical deficits and a progressive, debilitating impact on quality of life. Early identification and diagnosis of patients with chronic hypophosphatemia is crucial, and clinical management should be started as soon as possible to maximize the likelihood of improving health outcomes. Furthermore, in the absence of a universally accepted description for "chronic hypophosphatemia," a definition is proposed here that aims to raise awareness of these diseases, facilitate diagnosis, and guide optimal phosphate management strategies by improving monitoring and assessment of patient response to treatment. (c) 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).Peer reviewe

Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida

Genetic and antigenic characterization established the uniqueness of this virus circulating in dogs

Influenza A Virus (H3N8) in Dogs with Respiratory Disease, Florida

Genetic and antigenic characterization established the uniqueness of this virus circulating in dogs

Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer

Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylation in vitro and in vivo. Immunofluorescence microscopy and ATAC-See revealed the association of this modification with active chromatin. Brpf1 deletion obliterates the acylation in mouse embryos and fibroblasts. Moreover, we identify BRPF1 variants in 12 previously unidentified cases of syndromic intellectual disability and demonstrate that these cases and known BRPF1 variants impair H3K23 propionylation. Cardiac anomalies are present in a subset of the cases. H3K23 acylation is also impaired by cancer-derived somatic BRPF1 mutations. Valproate, vorinostat, propionate and butyrate promote H3K23 acylation. These results reveal the dual functionality of BRPF1-KAT6 complexes, shed light on mechanisms underlying related developmental disorders and various cancers, and suggest mutation-based therapy for medical conditions with deficient histone acylation