Rhythm as an independent determinant of developmental dyslexia.

Temporal accounts of Developmental Dyslexia (DD) postulate that a timing impairment plays an important role in this learning disorder. However, DD has been associated with timing disorders as well as other motor and cognitive dysfunctions. It is still unclear whether nonverbal timing skills per se may be considered as independent determinants of DD. In this study, we investigated the independent contribution of predictive timing to DD above and beyond the motor and cognitive dysfunctions typically associated with this disorder. Twenty-one children with DD (aged 8-12, nine females) and 27 controls (14 females) were evaluated on perceptual timing, finger tapping, fine motor control, as well as attention and executive tasks. Participants were native French speakers from various socioeconomic backgrounds. The performance of children with DD was poorer than that of controls in most of the tasks. Predictors of DD, as identified by logistic regression modeling, were beat perception and precision in tapping to the beat, which are both predictive timing variables, children's tapping rate, and cognitive flexibility. These data support temporal accounts of DD in which predictive timing impairments partially explain the core phonological deficit, independent from general motor and cognitive functioning, making predictive timing a valuable tool for early diagnosis and remediation of DD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Arithmetic Abilities in Children With Developmental Dyslexia: Performance on French ZAREKI-R Test.

A high comorbidity between reading and arithmetic disabilities has already been reported. The present study aims at identifying more precisely patterns of arithmetic performance in children with developmental dyslexia, defined with severe and specific criteria. By means of a standardized test of achievement in mathematics ( Calculation and Number Processing Assessment Battery for Children; von Aster & Dellatolas, 2006), we analyzed the arithmetic abilities of 47 French children with dyslexia attending 3rd, 4th, and 5th grade. Of them, 40% displayed arithmetic deficits, mostly with regard to number transcoding and mental calculation. Their individual profiles of performance accounted for varying strengths and weaknesses in arithmetic abilities. Our findings showed the pathway for the development of arithmetic abilities in children with dyslexia is not unique. Our study contrasts with the hypotheses suggesting the mutual exclusiveness of the phonological representation deficit and the core number module deficit.

TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons.

TSHZ3, which encodes a zinc-finger transcription factor, was recently positioned as a hub gene in a module of the genes with the highest expression in the developing human neocortex, but its functions remained unknown. Here we identify TSHZ3 as the critical region for a syndrome associated with heterozygous deletions at 19q12-q13.11, which includes autism spectrum disorder (ASD). In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs), and the human orthologs of these genes are strongly associated with ASD. Furthermore, mice heterozygous for Tshz3 show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings highlight essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly defined TSHZ3 deletion syndrome.

15q11.2 microdeletion (BP1-BP2) and developmental delay, behaviour issues, epilepsy and congenital heart disease: a series of 52 patients.

Proximal region of chromosome 15 long arm is rich in duplicons that, define five breakpoints (BP) for 15q rearrangements. 15q11.2 microdeletion between BP1 and BP2 has been previously associated with developmental delay and atypical psychological patterns. This region contains four highly-conserved and non-imprinted genes: NIPA1, NIPA2, CYFIP1, TUBGCP5. Our goal was to investigate the phenotypes associated with this microdeletion in a cohort of 52 patients. This copy number variation (CNV) was prevalent in 0.8% patients presenting with developmental delay, psychological pattern issues and/or multiple congenital malformations. This was studied by array-CGH at six different French Genetic laboratories. We collected data from 52 unrelated patients (including 3 foetuses) after excluding patients with an associated genetic alteration (known CNV, aneuploidy or known monogenic disease). Out of 52 patients, mild or moderate developmental delay was observed in 68.3%, 85.4% had speech impairment and 63.4% had psychological issues such as Attention Deficit and Hyperactivity Disorder, Autistic Spectrum Disorder or Obsessive-Compulsive Disorder. Seizures were noted in 18.7% patients and associated congenital heart disease in 17.3%. Parents were analysed for abnormalities in the region in 65.4% families. Amongst these families, 'de novo' microdeletions were observed in 18.8% and 81.2% were inherited from one of the parents. Incomplete penetrance and variable expressivity were observed amongst the patients. Our results support the hypothesis that 15q11.2 (BP1-BP2) microdeletion is associated with developmental delay, abnormal behaviour, generalized epilepsy and congenital heart disease. The later feature has been rarely described. Incomplete penetrance and variability of expression demands further assessment and studies.

Neuropsychological profile on the WISC-IV of French children with dyslexia.

This study examined the pattern of results on the Wechsler Intelligence Scale for Children (WISC-IV; French version) for 60 French children with dyslexia, from 8 to 16 years of age. Although use of WISC-III failed to clearly identify typical profiles and cognitive deficits in dyslexia, WISC-IV offers an opportunity to reach these objectives with new indexes and subtests. The mean performance analysis showed a Working Memory Index (WMI) at a limit level, significantly lower compared to the three other indexes. The WMI was the lowest index for 68% of the population studied and was significantly weaker for children with phonological dyslexia compared to children with surface dyslexia. WISC-IV evidenced preserved language and reasoning abilities in contrast to limited verbal working memory efficiency. Theoretical and clinical implications are discussed.

New syndromic form of benign hereditary chorea is associated with a deletion of TITF-1 and PAX-9 contiguous genes.

Benign hereditary chorea is a rare autosomal dominant disorder presenting with a childhood-onset and slowly progressive chorea. The objective of this study was to describe the clinical and genetic features of 3 patients who developed childhood-onset chorea. Three affected patients from three generations of a family with benign hereditary chorea associated with a multisystemic disorder of the basal ganglia, thyroid, lungs, salivary glands, bowels, and teeth. The TITF-1 gene was screened by microsatellite analysis, gene sequencing, and fluorescence in situ hybridization. Genetic analysis revealed a novel 0.9-Mb deletion on chromosome 14, which includes the TITF-1 and PAX9 genes. We have identified a novel deletion responsible for a new syndrome of benign hereditary chorea, including symptoms of brain-thyroid-lung syndrome associated with bowels, salivary glands, and teeth disorders. Associated signs, sometimes of slight expression, remain of high interest for the clinical and genetic diagnosis of benign hereditary chorea.

MRI in children with mental retardation.

BACKGROUND: In mental retardation (MR) an aetiological diagnosis is not always obtained despite a detailed history, physical examination and metabolic or genetic investigations. In some of these patients, MRI is recommended and may identify subtle abnormal brain findings. OBJECTIVE: We reviewed the cerebral MRI of children with non-specific mental retardation in an attempt to establish a neuroanatomical picture of this disorder. MATERIALS AND METHODS: Thirty children with non-specific MR were selected to undergo cerebral MRI. The examination included supratentorial axial slices, mid-sagittal images and posterior fossa coronal images. Brain malformations, midline and cerebellar abnormalities were studied. RESULTS: In 27 of 30 patients, the neuroimaging evaluation revealed a relatively high incidence of cerebral and posterior fossa abnormalities. The most frequent were: dysplasia of the corpus callosum (46%; hypoplasia, short corpus callosum and vertical splenium), partially opened septum pellucidum and/or cavum vergae (33%), ventriculomegaly (33%), cerebral cortical dysplasia (23%), subarachnoid space enlargement (16.6%), vermian hypoplasia (33%), cerebellar and/or vermian disorganised folia (20%), and subarachnoid spaces enlargement in the posterior fossa (20%). Other anomalies were: enlarged Virchow-Robin spaces (10%), white matter anomalies (10%) and cerebellar or vermian atrophy. CONCLUSIONS: MRI has shown a high incidence of subtle cerebral abnormalities and unexpected minor forms of cerebellar cortical dysplasia. Even if most of these abnormalities are considered as subtle markers of brain dysgenesis, their role in the pathogenesis of mental retardation needs further investigation.