1. Ames JL, Ladd-Acosta C, Fallin MD, Qian Y, Schieve LA, DiGuiseppi C, Lee LC, Kasten EP, Zhou G, Pinto-Martin J, Howerton EM, Eaton CL, Croen LA. Maternal Psychiatric Conditions, Treatment With Selective Serotonin Reuptake Inhibitors, and Neurodevelopmental Disorders. Biological psychiatry. 2021; 90(4): 253-62.

BACKGROUND: This study aims to clarify relationships of maternal psychiatric conditions and selective serotonin reuptake inhibitor (SSRI) use during preconception and pregnancy with risk of neurodevelopmental disorders in offspring. METHODS: We used data from the Study to Explore Early Development, a multisite case-control study conducted in the United States among children born between 2003 and 2011. Final study group classifications of autism spectrum disorder (ASD) (n = 1367), developmental delays or disorders (DDs) (n = 1750), and general population controls (n = 1671) were determined by an in-person standardized developmental assessment. Maternal psychiatric conditions and SSRI use during pregnancy were ascertained from both self-report and medical records. We used logistic regression to evaluate associations of ASD and DDs (vs. population controls) with maternal psychiatric conditions and SSRI treatment in pregnancy. To reduce confounding by indication, we also examined SSRI associations in analyses restricted to mothers with psychiatric conditions during pregnancy. RESULTS: Psychiatric conditions and SSRI use during pregnancy were significantly more common among mothers of children with either ASD or DDs than among population controls. Odds of ASD were similarly elevated among mothers with psychiatric conditions who did not use SSRIs during pregnancy (adjusted odds ratio 1.81, 95% confidence interval 1.44-2.27) as in mothers who did use SSRIs (adjusted odds ratio 2.05, 95% confidence interval 1.50-2.80). Among mothers with psychiatric conditions, SSRI use was not significantly associated with ASD in offspring (adjusted odds ratio 1.14, 95% confidence interval 0.80-1.62). Primary findings for DDs exhibited similar relationships to those observed with ASD. CONCLUSIONS: Maternal psychiatric conditions but not use of SSRIs during pregnancy were associated with increased risk of neurodevelopmental disorders in offspring.

Lien vers le texte intégral (Open Access ou abonnement)

2. Mailick MR, Hong J, Movaghar A, DaWalt L, Berry-Kravis EM, Brilliant MH, Boero J, Todd PK, Hall D. Mild Neurological Signs in FMR1 Premutation Women in an Unselected Community-Based Cohort. Movement disorders : official journal of the Movement Disorder Society. 2021; 36(10): 2378-86.

BACKGROUND: Premutation-sized (55-200) CGG repeat expansions in the FMR1 gene cause fragile X-associated tremor/ataxia syndrome (FXTAS). Most studies of premutation carriers utilized reverse ascertainment to identify patients, leading to a selection bias for larger repeats. As shorter CGG premutation repeats are common in the population, understanding their impact on health outcomes has a potentially large public health footprint. OBJECTIVE: The study’s objective was to compare an unselected group of premutation carriers (n = 35, 55-101 CGG repeats) with matched controls (n = 61, 29-39 CGG repeats) with respect to FXTAS-type signs using structured neurological assessments. METHODS: Three neurologists independently rated signs, using an adapted version of the FXTAS Rating Scale (Leehey MA, Berry-Kravis E, Goetz CG, et al. FMR1 CGG repeat length predicts motor dysfunction in premutation carriers. Neurology. 2008). This was a double-blind study, as genetic status (premutation vs. control) was known neither by the participants nor by any of the neurologists. Analyses controlled potentially confounding comorbid conditions in the electronic health record (eg, osteoarthritis and stroke) and probed the association of age with signs. RESULTS: Although there was no overall difference between carriers and controls, among individuals without any potentially confounding comorbid diagnoses, there was a statistically significant age-associated elevation in FXTAS-type signs in premutation carriers compared to controls. CONCLUSIONS: Among those who do not have other comorbid diagnoses, women who have CGG repeats at the lower end of the premutation range may be at greater risk for ataxia and parkinsonism than their age peers, although their overall risk of developing such clinical features is low. This study should provide reassurance to those who share characteristics with the present cohort. © 2021 International Parkinson and Movement Disorder Society.

Lien vers le texte intégral (Open Access ou abonnement)

3. Singh R, Cohen ASA, Poulton C, Hjortshøj TD, Akahira-Azuma M, Mendiratta G, Khan WA, Azmanov DN, Woodward KJ, Kirchhoff M, Shi L, Edelmann L, Baynam G, Scott SA, Jabs EW. Deletion of ERF and CIC causes abnormal skull morphology and global developmental delay. Cold Spring Harbor molecular case studies. 2021; 7(3).

The ETS2 repressor factor (ERF) is a transcription factor in the RAS-MEK-ERK signal transduction cascade that regulates cell proliferation and differentiation, and pathogenic sequence variants in the ERF gene cause variable craniosynostosis inherited in an autosomal dominant pattern. The reported ERF variants are largely loss-of-function, implying haploinsufficiency as a primary disease mechanism; however, ERF gene deletions have not been reported previously. Here we describe three probands with macrocephaly, craniofacial dysmorphology, and global developmental delay. Clinical genetic testing for fragile X and other relevant sequencing panels were negative; however, chromosomal microarray identified heterozygous deletions (63.7-583.2 kb) on Chromosome 19q13.2 in each proband that together included five genes associated with Mendelian diseases (ATP1A3, ERF, CIC, MEGF8, and LIPE). Parental testing indicated that the aberrations were apparently de novo in two of the probands and were inherited in the one proband with the smallest deletion. Deletion of ERF is consistent with the reported loss-of-function ERF variants, prompting clinical copy-number-variant classifications of likely pathogenic. Moreover, the recent characterization of heterozygous loss-of-function CIC sequence variants as a cause of intellectual disability and neurodevelopmental disorders inherited in an autosomal dominant pattern is also consistent with the developmental delays and intellectual disabilities identified among the two probands with CIC deletions. Taken together, this case series adds to the previously reported patients with ERF and/or CIC sequence variants and supports haploinsufficiency of both genes as a mechanism for a variable syndromic cranial phenotype with developmental delays and intellectual disability inherited in an autosomal dominant pattern.

Lien vers le texte intégral (Open Access ou abonnement)

4. Uzonyi TE, Crais ER, Watson LR, Nowell SW, Baranek GT, Turner-Brown LM. Measuring Transactional Engagement Among Young Children with Elevated Likelihood for Later Autism Spectrum Disorder Diagnosis. Journal of autism and developmental disorders. 2021.

This analytical study documented the presence of transactions in parent-child engagement within a sample of young children at an elevated likelihood for an eventual diagnosis of autism spectrum disorder (ASD). Specifically, the study examined the establishment of transactional engagement through reciprocal behaviors between parents and their young children at-risk for ASD. In the study sample, established transactional engagement occurred at a higher rate than other levels of engagement. Additionally, transactional engagement had a higher likelihood of being established when parents initiated. Post-hoc analyses revealed possible early markers of ASD within a certain behavior displayed in transactions. This study signifies the initial efforts in identifying transactions within parent-child engagement, and foremost, how transactional engagement is established.

Lien vers le texte intégral (Open Access ou abonnement)

5. Van Hecke R, Deconinck FJA, Wiersema JR, Clauws C, Danneels M, Dhooge I, Leyssens L, Van Waelvelde H, Maes L. Balanced Growth project: a protocol of a single-centre observational study on the involvement of the vestibular system in a child’s motor and cognitive development. BMJ open. 2021; 11(6): e049165.

INTRODUCTION: The involvement of the vestibular system in the motor and higher (cognitive) performances of typically developing or vestibular-impaired children is currently unknown or has only scarcely been explored. Interestingly, arguments for an interaction between vestibular, motor and cognitive functions in children can also be supported by research on children known for their difficulties in motor and/or cognitive processing (eg, children with neurodevelopmental disorders (NDD)), as they often present with vestibular-like characteristics. Therefore, in order to elucidate this interaction, and to increase the understanding of the pathophysiology and symptomatology of vestibular disorders and NDD in children, the Balanced Growth project was developed. It includes the following objectives: (1) to understand the association between motor skills, cognitive performances and the vestibular function in typically developing school-aged children, with special focus on the added value of the vestibular system in higher cognitive skills and motor competence; (2) to investigate whether a vestibular dysfunction (with/without an additional auditory disease) has an impact on motor skills, cognitive performances and motor-cognitive interactions in children and (3) to assess if an underlying vestibular dysfunction can be identified in school-aged children with NDD, with documentation of the occurrence and characteristics of vestibular dysfunctions in this group of children using an extensive vestibular test battery. METHODS AND ANALYSIS: In order to achieve the objectives of the observational cross-sectional Balanced Growth study, a single-task and dual-task test protocol was created, which will be performed in three groups of school-aged children (6-12 years old): (1) a typically developing group (n=140), (2) (audio) vestibular-impaired children (n=30) and (3) children with an NDD diagnosis (n=55) (ie, autism spectrum disorder, attention deficit/hyperactivity disorder and/or developmental coordination disorder). The test protocol consists of several custom-made tests and already existing validated test batteries and includes a vestibular assessment, an extensive motor assessment, eight neurocognitive tests, a cognitive-motor interaction assessment and includes also additional screenings to control for potential confounding factors (eg, hearing status, intelligence, physical activity, etc). ETHICS AND DISSEMINATION: The current study was approved by the ethics committee of Ghent University Hospital on 4 June 2019 with registration number B670201940165 and is registered at Clinical Trials (clinicaltrials.gov) with identifier NCT04685746. All research findings will be disseminated in peer-reviewed journals and presented at vestibular as well as multidisciplinary international conferences and meetings. TRIAL REGISTRATION NUMBER: NCT04685746.

Lien vers le texte intégral (Open Access ou abonnement)