A founder truncating variant in GDF1 causes autosomal‐recessive right isomerism and associated congenital heart defects in multiplex Arab kindreds

The genetic basis of congenital heart malformations associated with disruption of left–right (L–R) asymmetry is broad and heterogenous, with variants in over 25 genes implicated thus far. Of these, deleterious variants in the Growth/Differentiation Factor 1 (GDF1) gene have been shown to cause heterotaxy with varied complex heart malformations of left–right patterning, in 23 individuals reported to date, either in monoallelic or biallelic state. We report three unrelated individuals exhibiting right isomerism with congenital heart defects, each originating from a consanguineous kindred of Arab‐Muslim descent. Using whole exome sequencing, a shared novel homozygous truncating c.608G > A (p.W203*) variant in the GDF1 gene was revealed as the molecular basis of their disease. Subsequently, targeted sequencing of this variant showed full segregation with the disease in these families, with a total of over 15 reportedly affected individuals, enabling genetic counseling, prenatal diagnosis, and planning of future pregnancies. Our findings further confirm the association of biallelic GDF1 variants, heterotaxy and congenital heart defects of left–right patterning, and expand the previously described phenotypic spectrum and mutational profile. Moreover, we suggest targeted screening for the p.W203* variant in relevant clinical circumstances.     

Parents of adolescents with psychiatric disorders: insight into the disorder,self-stigma and parental stress

Background

Parents of adolescents with mental disorders experience stress partially due to the way they perceive and experience their offspring's disorder. The current study assessed the mediator role of self-stigma in the relationship between insight into the disorder and parental stress of parents of adolescents with mental disorders.

Method

A total of 37 parents of adolescents with psychiatric disorders were assessed for their level of insight, self-stigma and parental stress.

Results

The hypothesized mediation model was confirmed and is consistent with previous study on parents of adults with severe mental illness.

Discussion

The positive association between insight and parental stress is mediated by these parents' self-stigma, suggesting that insight increases the self-stigma, which in turn increases the parental stress. These results may have clinical implications with regard to the treatment of the family of adolescents with mental disorders.     

Response of ophthalmologists in Israel to the novel coronavirus (2019-nCoV) outbreak

Graefe's Archive for Clinical and Experimental Ophthalmology - The coronavirus disease (COVID-19) pandemic has evolved into a formidable healthcare crisis. Ophthalmologists are at daily...     

Ultrasound-Guided OnabotulinumtoxinA Injections to Treat Oromandibular Dystonia in Cerebral Palsy

Cerebral palsy (CP) is a group of non-progressive disorders of motor function in children resulting from an injury to an immature brain. In addition to abnormal limb and trunk movement, individuals with CP can experience involuntary muscle contractions of the lower facial muscle groups, causing oromandibular dystonia (OMD). Contraction of the lateral pterygoids and submandibular muscles depresses the mandible. OMD involving the lateral pterygoids can therefore lead to involuntary jaw opening posture, affecting the ability to feed and speak effectively. We present a case series of five patients with CP and OMD that received novel ultrasound-guided onabotulinumtoxinA to the lateral pterygoid muscles. Our goal was to determine if chemodenervation would improve the mouth-closing ability, thus in turn improving the ability to swallow, chew, manage secretions, and communicate. We describe this unique injection method and report a subjective improvement in eating abilities and communication, in addition to a positive upward trend in most patients’ weights, with no significant adverse side effects.     

The electrodiagnostic examination of psychogenic swallowing disorders

The article discusses the usefulness and technique of investigation of suspected psychogenic dysphagia by surface electromyography (sEMG) of deglutition. Thirty-two patients with suspected psychogenic dysphagia (Group 1) and 40 healthy individuals (Group 2) were involved in the study. The timing, amplitude and graphic patterns of activity of the masseter, submental, infrahyoid and trapezius muscles were examined during voluntary single water swallows (“normal”), and continuous drinking of 100 cc of water. The muscle activity in oral, pharyngeal and initial oesophageal stages of swallowing was measured, and graphic records were evaluated in relation to timing and voltage. Globus hystericus was found in only 14 patients of the Group 1 (43.75%). The main sEMG pattern of psychogenic dysphagia is a lack of any pathologic changes of timing, voltage and graphic patterns of deglutition. In 28% of cases tension of skeletal muscles not involved in deglutition was observed during single swallowing (vs. 0% in controls). Psychogenic/hysteria-conversion dysphagia has no pathologic sEMG patterns associated with deglutition. Skeletal muscle tension during deglutition, being observed in some cases has no connection with the act of swallowing itself. Surface EMG, being non-invasive and non-radiographic, can be used for screening purposes for patients with dysphagia thus avoiding expensive and time-consuming investigation.     

A community based study of failure to thrive in Israel

OBJECTIVE: To examine the characteristics of infants suffering from failure to thrive in a community based cohort in Israel and to ascertain the effect of failure to thrive on their cognitive development. METHODS: By review of records maintained at maternal and child health clinics in Jerusalem and the two of Beit Shemesh, epidemiological data were obtained at age 15 months on a cohort of all babies born in 1991. For each case of failure to thrive, a matched control was selected from the same maternal and child health clinic. At age 20 months, cognitive development was measured, and at 25 months a home visit was carried out to assess maternal psychiatric status by questionnaire, and the HOME assessment was performed to assess the home environment. RESULTS: 3.9% of infants were found to have fallen below the third centile in weight for at least three months during the first year of life. Infants with failure to thrive did not differ from the general population in terms of obstetric or neonatal complications, birth order, or parents' ethnic origin, age, or years of education. The infants with failure to thrive did have lower birthweights and marginally smaller head circumferences at birth. Developmental assessment at 20 months of age showed a DQ of 99.7 v 107.2 in the matched controls, with 11.5% having a DQ below 80, as opposed to only 4.6% of the controls. No differences were found in maternal psychiatric problems as measured by a self report questionnaire. There were, however, significant differences in subscales of the HOME scale. CONCLUSIONS: (1) Infants who suffered from failure to thrive had some physiological predispositions that put them at risk; (2) failure to thrive may be an early marker of families providing suboptimal developmental stimulation.     

Is propofol safe for procedural sedation in children? A prospective evaluation of propofol versus ketamine in pediatric critical care

OBJECTIVES: To compare propofol with ketamine sedation delivered by pediatric intensivists during painful procedures in the pediatric critical care department (PCCD). DESIGN: Prospective 15-month study. SETTING: An 18-bed multidisciplinary, university-affiliated PCCD. INTERVENTIONS: All children were randomized to the propofol or ketamine protocol according to prescheduled procedure dates. Propofol was delivered by continuous infusion after a loading bolus dose and a minidose of lidocaine (PL). Ketamine was given as a bolus injection together with midazolam and fentanyl (KMF). Repeated bolus doses of both drugs were given to achieve the desired level of anesthesia. The studied variables included procedures performed, anesthetic drug doses, procedure and recovery durations, and side effect occurrence. The patient's parents, PCCD nurse and resident physician, pediatric intensivist, and the physician performing the procedure graded the adequacy of anesthesia. MEASUREMENTS AND MAIN RESULTS: Of the 105 procedures in 98 children, PL sedation was used in 58 procedures, and KMF was used in 47. Recovery time was 23 mins for PL and 50 mins for KMF, and total PCCD monitoring was 43 mins for PL and 70 mins for KMF. Five children (10.6%) in the KMF group and in none in the PL group experienced discomfort during emergence from sedation. Transient decreases in blood pressure, partial airway obstruction, and apnea were more frequent in the PL than in the KMF sedation. All procedures were successfully completed, and no child recalled undergoing the procedure. The overall sedation adequacy score was 97% for PL and 92% for KMF (p <.05). CONCLUSIONS: Both PL and KMF anesthesia are effective in optimizing comfort in children undergoing painful procedures. PL scored better by all evaluators, recovery from PL anesthesia after procedural sedation was more rapid, total PCCD stay was shorter with PL, and emergence from PL was smoother than with KMF. Because transient respiratory depression and hypotension are associated with PL, it is considered safe only in a monitored environment (e.g., a PCCD).     

Genetic diagnosis and renal biopsy findings in the setting of a renal genetics clinic

As genetic testing becomes more available, its utilization as an early diagnostic tool in nephrology is more common. The objective of the study is to examine diagnostic agreement between the renal biopsy findings and genetic diagnoses. A retrospective study was conducted in February 2022. A total of 28 patients had both genetic diagnosis and histologic results (n = 1 nephrectomy, n = 27 biopsy). We collected clinical, renal biopsy findings, and genetic information. The relationship between the histologic findings and the genetic diagnoses was classified as: concordant, nonspecific, and discordant. A total of 15 males and 13 females were included (mean age = 9.6 years). Clinical suspicion of Alport syndrome was the most common reason for referral (n = 11, 39.3%), followed by nephrotic syndrome (n = 8, 28.5%), “other” (n = 6, 21.4%), cystic kidney disease (n = 1, 3.6%), isolated hematuria (n = 1, 3.6%), and non-nephrotic proteinuria (n = 1, 3.6%). The overall concordance rate between renal histologic and genetic diagnoses was 71.4% (20/28), nonspecific biopsy results were observed in 17.9% (5/28), and discordant results were observed in 10.7% (3/28). All patients referred for suspected Alport Syndrome had pathogenic/likely pathogenic variants in one of the COL4A genes. Two cases of Lowe syndrome and one of PAX2-associated nephropathy had discordant histology findings. Agreement between renal histologic findings and genetic results varies based on the reason for referral. There was a complete agreement for patients referred for Alport Syndrome; However, there were examples that renal biopsy showed secondary findings that were not specifically associated with the underlying genetic results.     

QT interval and dispersion in very young children treated with antipsychotic drugs: a retrospective chart review

OBJECTIVES AND BACKGROUND: QT dispersion (QTd) is a measure of interlead variations of the surface 12-lead electrocardiogram (ECG). Increased QTd, found in various cardiac diseases, reflects cardiac instability and risk for lethal cardiac arrhythmias. Research suggests a link between psychotropic treatment, ECG abnormalities (QT prolongation), and increased sudden cardiac mortality rates. Reports of sudden death in children treated with psychotropic drugs have raised concerns about cardiovascular monitoring and risk stratification. QTd analysis has not been investigated in very young children treated with antipsychotic drugs. In the present retrospective chart review study, we calculated QT interval, QTd, and their rate-corrected values in very young children treated with antipsychotics. METHODS: The charts of 12 children (ages 5.8 +/- 0.98 yr; 4 girls, 8 boys) were examined before initiation of antipsychotic treatment [risperidone (n = 7), clotinapine (n = 1), and propericiazine (n = 4)] and during the maintenance period after achieving a positive clinical response. Three children were concomitantly maintained on methylphenidate. QT interval, QTd, and their rate-corrected values were calculated. RESULTS: QT interval, QTd, and their rate-corrected values were all within normal values both before and after successful drug treatment. CONCLUSIONS: This preliminary, naturalistic, small-scale study suggests that antipsychotic treatment, with or without methylphenidate, in very young children is not commonly associated with significant alterations of QT interval and dispersion, suggesting the relative safety of these agents in this unique age group.