Marco Carrozzi

Extra-large letter spacing improves reading in dyslexia.

Although the causes of dyslexia are still debated, all researchers agree that the main challenge is to find ways that allow a child with dyslexia to read more words in less time, because reading more is undisputedly the most efficient intervention for dyslexia. Sophisticated training programs exist, but they typically target the component skills of reading, such as phonological awareness. After the component skills have improved, the main challenge remains (that is, reading deficits must be treated by reading more—a vicious circle for a dyslexic child). Here, we show that a simple manipulation of letter spacing substantially improved text reading performance on the fly (without any training) in a large, unselected sample of Italian and French dyslexic children. Extra-large letter spacing helps reading, because dyslexics are abnormally affected by crowding, a perceptual phenomenon with detrimental effects on letter recognition that is modulated by the spacing between letters. Extra-large letter spacing may help to break the vicious circle by rendering the reading material more easily accessible.

Associations of Prenatal Mercury Exposure From Maternal Fish Consumption and Polyunsaturated Fatty Acids With Child Neurodevelopment: A Prospective Cohort Study in Italy

Background Mercury is a neurotoxin, and limited prenatal exposure to it can affect long-term child neurodevelopment. However, results of epidemiologic studies of such exposure have been inconsistent. We examined the association of prenatal mercury exposure from maternal fish consumption with child neurodevelopment in northern Italy. Methods A population-based cohort of 606 children and their mothers was studied from pregnancy to age 18 months. Mercury levels were measured in maternal hair and blood during pregnancy and in umbilical cord blood and breast milk. Levels of polyunsaturated fatty acids (PUFAs) were measured in maternal serum. Maternal and child intakes of fish were assessed by using a food frequency questionnaire. The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) was used to evaluate child neurodevelopment. Multivariate linear regression was used to examine the association of mercury exposure with BSID-III scores, after controlling for maternal fish intake, PUFAs during pregnancy, and several other confounders. Results Mean weekly fish intake during pregnancy was less than 2 servings. Mercury concentrations in biological samples were low (mean, 1061 ng/g in hair) and moderately correlated with fish intake, particularly of carnivorous species. Maternal ω-3 PUFA concentrations were poorly correlated with fish intake. Maternal intelligence quotient (IQ) and child intake of fish were significantly associated with neurodevelopment scores. In multivariate models, the level of Hg exposure was not associated with neurodevelopmental performance at 18 months. Conclusions In this Italian population, neurodevelopment at 18 months was associated with child intake of fresh fish and maternal IQ rather than with mercury exposure. The expected beneficial effect of maternal fish intake (from maternal ω-3 PUFAs) was not found.

The Submerged Dyslexia Iceberg: How Many School Children Are Not Diagnosed? Results from an Italian Study

Background Although dyslexia is one of the most common neurobehavioral disorders affecting children, prevalence is uncertain and available data are scanty and dated. The objective of this study is to evaluate the prevalence of dyslexia in an unselected school population using clearly defined and rigorous diagnostic criteria and methods. Methods Cross sectional study. We selected a random cluster sample of 94 fourth grade elementary school classes of Friuli Venezia Giulia, a Region of North Eastern Italy. We carried out three consecutive levels of screening: the first two at school and the last at the Neuropsychiatry Unit of a third level Mother and Child Hospital. The main outcome measure was the prevalence of dyslexia, defined as the number of children positive to the third level of screening divided by the total number of children enrolled. Results We recruited 1774 children aged 8–10 years, of which 1528 received parents’ consent to participate. After applying exclusion criteria, 1357 pupils constituted the final working sample. The prevalence of dyslexia in the enrolled population ranged from 3.1% (95% CI 2.2–4.1%) to 3.2% (95% CI 2.4–4.3%) depending on different criteria adopted. In two out of three children with dyslexia the disorder had not been previously diagnosed. Conclusions This study shows that dyslexia is largely underestimated in Italy and underlines the need for reliable information on prevalence, in order to better allocate resources both to Health Services and Schools.

Supernumerary ring chromosome 8: Clinical and molecular cytogenetic characterization in a case report

We report on a 3‐year‐old male with developmental delay, autistic behavior, and minor abnormalities consistent with trisomy 8 syndrome whose cytogenetic analysis revealed mosaicism for a supernumerary ring chromosome (SRC). Fluorescence in situ hybridization (FISH) studies, using centromeric and yeast artificial chromosome (YAC) probes, were performed to characterize further the supernumerary chromosome. The ring origin has been detected from the short arm of chromosome 8, resulting in r(8)(p10p23.1). Moreover, uniparental disomy (UPD) using microsatellite analysis was excluded. To our knowledge a total of 25 cases, confirmed by FISH, have been reported with either supernumerary marker or ring chromosome 8. We present a detailed clinical and molecular cytogenetic characterization of this additional case in order to better define the genotype–phenotype correlation.

Does the 1.5 Mb microduplication in chromosome band Xp22.31 have a pathogenetic role? New contribution and a review of the literature†‡

Does the 1.5 Mb Microduplication in Chromosome Band Xp22.31 Have a Pathogenetic Role? New Contribution and a Review of the Literature Flavio Faletra,* Adamo Pio D’Adamo, Maria Santa Rocca, Marco Carrozzi, Maria Dolores Perrone, Vanna Pecile, and Paolo Gasparini Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy Institute for Maternal and Child Health, IRCCS ‘‘Burlo Garofolo’’, University of Trieste, Trieste, Italy

Neuromotor Deficits in Developmental Coordination Disorder: Evidence from a Reach-to-Grasp Task.

Developmental coordination disorder (DCD) has been classified as a specific learning disability, nonetheless the underlying cognitive mechanisms are still a matter of discussion. After a summary of the main hypotheses on the principal neuromotor causes of DCD, this study applies a causal model framework to describe the possible coexistence of more than one deficit in this disorder. For this purpose, kinematic analysis was applied to an ecological task, the reach-to-grasp action, introducing the manipulation of three variables: vision, distance and object size. After a thorough neurological and neuropsychological evaluation, 9 children with DCD (7-9 years old) were selected and compared to 27 age-matched control children. The results suggest that children with DCD have a normal neurological characterization of the reaching and grasping movements, in terms of proximal to distal action, but their grasping aperture (MGA) was always wider with respect to controls, particularly when vision was not allowed. In addition, the performance of children with DCD was always slower, more dependent on vision and more variable than that of controls. The MGA of children with DCD could be explained by a deficit in the internal construction of movement for a forward model, while slowness could be related to a control problem in the neuronal firing of the muscles. The idea of a possible coexistence of these two deficits is discussed in accordance to a causal model framework and also addressed considering recent neurophysiologic evidences.

Chronic Tension-Type Headache in Adolescents. Clinical and Psychological Characteristics Analyzed Through Self- and Parent-Report Questionnaires

OBJECTIVES To analyze the relation between the symptoms reported by adolescents with chronic tension-type headache (CTTH) and their perception of their emotional and behavioral functioning. METHODS Two groups of adolescents (clinical group, n = 48; control group, n = 135) and their parents (clinical group, n = 42; control group, n = 128) were studied, respectively, with the Youth Self-Report Questionnaire and the Child Behavior Checklist. Moreover, a secondary analysis was performed, identifying another subgroup of adolescents who reported having headaches. RESULTS The clinical group of adolescents obtained higher scores than the control group in Internalizing Syndrome; Aggressive Behavior for Externalizing Syndrome; Social, Thought, and Attention Problems; and in all Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)-oriented scales (except conduct problems). Differences between the two groups of parents were found in all the scales. The controls reporting headaches obtained interesting intermediate scores. CONCLUSIONS Adolescents with CTTH show greater emotional and behavioral problems than their healthy peers. Consequently, clinical approaches for proper diagnosis and treatment need to adopt a multidisciplinary prospective.

Carbamazepine Hypersensitivity Syndrome Triggered by a Human Herpes Virus Reactivation in a Genetically Predisposed Patient

A case of severe hypersensitivity syndrome, triggered by carbamazepine in the presence of a concomitant active human herpes virus (HHV) 6 and 7 infection is described. To further understand the molecular mechanism of this adverse reaction, analyses of the genetic variants of human leukocyte antigen (HLA) and of the epoxide hydrolase gene (EPHX1), previously associated with carbamazepine hypersensitivity, were performed. A lymphocyte transformation test (LTT) was conducted in order to detect drug-specific lymphocytes. In the hypersensitive patient, 2 genetic factors previously associated with intolerance to carbamazepine were detected: the allele HLA-A*3101 and homozygosity for the variant allele of SNP rs1051740 in EPHX1. Drug-specific lymphocytes could be detected by LTT when the HHV was active (positive PCR for viral DNA and increased anti-HHV 6 IgG titer), but not when it was no longer active. In conclusion, we document a case of severe carbamazepine hypersensitivity triggered by viral reactivation in a patient presenting the interaction of 2 unfavorable genetic factors.

Stem cells in severe infantile spinal muscular atrophy (SMA1)

I read with great interest the article by Scheidl et al. [1] focused on the ultrasonography findings of the acquired demyelinating sensory and motor neuropathy (MADSAM). The authors depicted for the first time in the literature, that focal nerve enlargements can be detected by ultrasound in MADSAM, at sites of previous conduction blocks, well after complete clinical and electrophysiological resolution. This observation highlights in my opinion two important aspects in the clinical course of the disease. On one side, it shows that ultrasonographic morphological changes may outlast functional recovery in such demyelinating neuropathies. On the other side, this study highlights the fact that although the clinical course of the disease is expected to be predominantly in the upper extremities, morphological changes to the nerves of the lower extremities can be detected by ultrasound prior to clinical and electrophysiological affection. A similar sonographical observation has been done only in the case of multifocal motor neuropathy (MMN) by Beekman et al. [2]. They reported in a study of 21 patients, that a sonographic enlargement could be found not only in nerve segments without conduction abnormalities indicating demyelination, but also in nerves with normal conduction. In our neurophysiologic and ultrasound lab we recently started to perform ultrasound in patients affected from immune-mediated neuropathies. Experiencing a case of a MADSAM neuropathy with disease course over 2 years, we detected sonographically a hypertrophy of the median and ulnar nerve in the forearm on both sides, but no pathological findings could be detected in the lower extremities. The site where the hypertrophy was detected in ultrasound correlated with the site of conduction block in the electrophysiological studies. Considering the study from Scheidl et al. and our findings we would like to draw attention to the usefulness of ultrasonography for detecting and diagnosing segmental lesions of the peripheral nerves in MADSAM and other immune-mediated neuropathies. These findings indicate that the disease process in MADSAM is more widespread than expected on the basis of clinical and electrophysiologic abnormalities. In our case though, we could not detect any pathological abnormalities in the lower extremities, so the time course of the disease may play an important role for the detection of these changes. Unfortunately there are no histologic studies of nerves in MADSAM without electrophysiologic abnormalities that could confirm these ultrasound findings. These ultrasound observations could help though to understand the underlying mechanisms of nerve damage and facilitate the development of more effective treatments.

Two novel POLG mutations causing hepatic mitochondrial DNA depletion with recurrent hypoketotic hypoglycaemia and fatal liver dysfunction

BACKGROUND Inherited mtDNA depletion syndromes (MDS) are a group of severe mitochondrial disorders resulting from defects in nucleus-encoded factors and often associated with severe or fatal liver failure. PATIENT In this article, we describe the case of an 18-month-old patient with recurrent hypoketotic hypoglycaemia and fatal hepatic dysfunction with liver mtDNA depletion. METHODS The assessment of mtDNA copy number was performed on leucocytes, liver and muscle biopsy by Quantitative Real Time PCR and total RNA from liver biopsy was used as a template to amplify the cDNA of the POLG1 gene. RESULTS Sequence analysis identified two previously undescribed mutations (1868T>G and 2263A>G) located in the gene coding the catalytic subunit of mitochondrial DNA polymerase gamma (POLG), predicting an L623W and K755E amino acid change, respectively. Both mutations were located in the highly conserved linker region of the protein and were absent in more than 200 healthy unrelated control subjects. The identification of these two mutations allowed us to perform genetic counselling and prenatal diagnosis. CONCLUSION Our data further expand the spectrum of POLG1 gene mutations and the unique phenotype reported (late onset isolated liver disease without lactic acidosis) increase the variability of clinical presentations associated with mutations in this gene.