Prenatal counseling: Guidelines for the care of people with spina bifida.

As the diagnosis of Spina Bifida (SB) is often made prenatally, SB-specific prenatal counseling is needed. It is essential to provide information about medical care and lifelong impact of this diagnosis, treatment options available to women carrying fetuses affected, and resources that will assist in the care of individuals with SB. This article outlines the SB Prenatal Counseling Guidelines from the 2018 Spina Bifida Association's Fourth Edition of the Guidelines for the Care of People with Spina Bifida and acknowledges that further research in SB prenatal counseling is warranted.

Normal IQ is possible in Smith-Lemli-Opitz syndrome.

Children with Smith-Lemli-Opitz syndrome (SLOS) are typically reported to have moderate to severe intellectual disability. This study aims to determine whether normal cognitive function is possible in this population and to describe clinical, biochemical and molecular characteristics of children with SLOS and normal intelligent quotient (IQ). The study included children with SLOS who underwent cognitive testing in four centers. All children with at least one IQ composite score above 80 were included in the study. Six girls, three boys with SLOS were found to have normal or low-normal IQ in a cohort of 145 children with SLOS. Major/multiple organ anomalies and low serum cholesterol levels were uncommon. No correlation with IQ and genotype was evident and no specific developmental profile were observed. Thus, normal or low-normal cognitive function is possible in SLOS. Further studies are needed to elucidate factors contributing to normal or low-normal cognitive function in children with SLOS.

The effectiveness of bowel and bladder interventions in children with spina bifida.

AIM: Using the World Health Organization International Classification of Functioning, Disability and Health (ICF), the aim of this study was to identify effective strategies for managing urinary and bowel complications resulting from spina bifida. METHOD: Charts of 210 children between 4- and 13-years-old with spina bifida were reviewed to quantify medical interventions and continence status. Standardized quality of life (QOL) questionnaires were administered to a subset of participants; child and parent interviews were carried out to examine the experience of living with bowel and bladder incontinence. Practitioners were also interviewed to understand their perspectives of intervention effectiveness. RESULTS: Chart review indicated less than half of children were continent for bowel and bladder. More variability existed in bowel continence programs, and practitioners considered bowel continence more difficult to achieve than bladder continence. No significant associations were found between continence status and QOL measures. Interviews, however, reflected how managing continence at home and school more broadly affects QOL. Among practitioners, some focused primarily on optimizing physical health while others focused on activity and participation. INTERPRETATION: While continence is a goal, programs used to achieve this are individualized and outcomes may be affected by differential treatment effects, environmental factors, and/or stigma experienced by children.

Feeding impairments associated with plasma sterols in Smith-Lemli-Opitz syndrome.

OBJECTIVE: To quantitatively evaluate feeding impairment in children with Smith-Lemli-Opitz syndrome (SLOS) and to correlate feeding impairment with clinical and biochemical indices of disease severity. STUDY DESIGN: The study subjects were 26 children with SLOS ranging in age from 0.4 to 19 years. Clinical severity was measured using an existing scoring system. We created a tool to quantitatively evaluate feeding. Plasma sterol concentrations were measured, and statistical associations (correlations) with feeding scores were calculated. RESULTS: Oral hyposensitivity or hypersensitivity, adverse behaviors, and risk for dysphagia were seen in ∼65% of the children with SLOS. Thirteen of the 26 children experienced failure to thrive, and 10 children required gastrostomy. Plasma concentration of 7-dehydrocholesterol, as a measure of severity, was correlated with total feeding score and oral function subcategory score (P < .001) and less so with oral structure score, adverse behaviors, or dysphagia. Correlations with cholesterol concentrations were less statistically significant. A plasma 7-dehydrocholesterol concentration >0.24 mmol/L or cholesterol concentration <1.95 mmol/L was predictive of gastrostomy tube use. Feeding impairments may improve with age. CONCLUSION: Feeding impairment is common and complex in patients with SLOS. Our findings confirm that oral sensitivities, adverse feeding behaviors, and risk of oral phase dysphagia are amenable to quantitative evaluation and analysis. Feeding difficulties in children with SLOS are correlated with plasma sterol concentrations, suggesting a link between the biochemical severity of SLOS and feeding function. These findings expand the behavioral phenotype of SLOS and begin to provide insight into the biological causes of feeding difficulties.

Mutations in γ adducin are associated with inherited cerebral palsy.

OBJECTIVE: Cerebral palsy is estimated to affect nearly 1 in 500 children, and although prenatal and perinatal contributors have been well characterized, at least 20% of cases are believed to be inherited. Previous studies have identified mutations in the actin-capping protein KANK1 and the adaptor protein-4 complex in forms of inherited cerebral palsy, suggesting a role for components of the dynamic cytoskeleton in the genesis of the disease. METHODS: We studied a multiplex consanguineous Jordanian family by homozygosity mapping and exome sequencing, then used patient-derived fibroblasts to examine functional consequences of the mutation we identified in vitro. We subsequently studied the effects of adducin loss of function in Drosophila. RESULTS: We identified a homozygous c.1100G>A (p.G367D) mutation in ADD3, encoding gamma adducin in all affected members of the index family. Follow-up experiments in patient fibroblasts found that the p.G367D mutation, which occurs within the putative oligomerization critical region, impairs the ability of gamma adducin to associate with the alpha subunit. This mutation impairs the normal actin-capping function of adducin, leading to both abnormal proliferation and migration in cultured patient fibroblasts. Loss of function studies of the Drosophila adducin ortholog hts confirmed a critical role for adducin in locomotion. INTERPRETATION: Although likely a rare cause of cerebral palsy, our findings indicate a critical role for adducins in regulating the activity of the actin cytoskeleton, suggesting that impaired adducin function may lead to neuromotor impairment and further implicating abnormalities of the dynamic cytoskeleton as a pathogenic mechanism contributing to cerebral palsy.