Publications by authors named "Ilaria Contaldo"

21 Publications

  • Page 1 of 1

A novel homozygous variant in JAM3 gene causing hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts (HDBSCC) with neonatal onset.

Neurol Sci 2021 Jul 22. Epub 2021 Jul 22.

Università Cattolica del Sacro Cuore, Rome, Italy.

Background: JAM3 gene, located on human chromosome 11q25, encodes a member of the junctional adhesion molecule (JAM) family. Mutations of this gene are associated with hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts (HDBSCC).

Case Report: Herein, we present a newborn male with a prenatal suspicion of bilateral cataracts but without fetal ultrasound findings of cortical malformations. He was postnatally diagnosed with a clinical picture of HDBSCC and Early-onset Developmental and Epileptic Encephalopathy (DEE), associated to a homozygous variant of JAM3 gene.

Conclusion: Identification of this variant in affected individuals has implications for perinatal and postnatal management and genetic counseling. To the best of our knowledge, this is the first case reported of a child with a JAM3 variant in Italy, from a different ethnic background than the other reported children until now (Saudi Arabian, Turkish, Afghani, and Moroccan origin). JAM3 screening could be requested in prenatal diagnosis of fetal congenital cataracts and included in Next-Generation DNA Sequencing panels.
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http://dx.doi.org/10.1007/s10072-021-05480-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295029PMC
July 2021

Adult phenotype in Koolen-de Vries/ haploinsufficiency syndrome.

J Med Genet 2020 Dec 24. Epub 2020 Dec 24.

Dipartimento Universitario Scienze della Vita e Sanità Pubblica, Sezione di Medicina Genomica, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Roma, Italy

Background: Koolen-de Vries syndrome (KdVS) is a multisystem neurodevelopmental disorder caused by 17q21.31 deletions or mutations in . It was mainly described in children.

Methods: A retrospective study on 9 subjects aged 19-45 years and revision of 18 literature patients, with the purpose to get insights into the phenotypic evolution with time, and into the clinical manifestations in adulthood.

Results: Seven patients had a 17q21.31 deletion and two a point mutation in . All had intellectual disability, which was mild in five (56%) and moderate in four (44%). Epilepsy was diagnosed in four subjects (44%), with onset from 1 to 7 years and full remission before 9 years in 3/4 patients. Scoliosis affected seven individuals (77.7%) and it was substantially stable with age in 5/7 patients, allowing for simple daily activities. Two subjects had severely progressive scoliosis, which was surgically corrected. Overweight or true obesity did occur after puberty in six patients (67%). Behaviour abnormalities were recorded in six patients (67%). The facial phenotype slightly evolved with time to include thick eyebrows, elongated nose and pronounced pointed chin. Despite behaviour abnormalities, happy disposition and sociable attitudes were common. Half of patients had fluent language and were good at writing and reading. Rich language, although limited to single words or short sentences, and very limited or absent skills in writing and reading were observed in the remaining patients. Autonomy in daily activities and personal care was usually limited.

Conclusions: Distinctive features in adult KdVS subjects include intellectual disability, overweight/obesity, behaviour abnormalities with preserved social interest, ability in language, slight worsening of the facial phenotype and no seizures.
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http://dx.doi.org/10.1136/jmedgenet-2020-107225DOI Listing
December 2020

Embryopathy Following Maternal Biliopancreatic Diversion: Is Bariatric Surgery Really Safe?

Obes Surg 2021 Jan 28;31(1):445-450. Epub 2020 Jul 28.

Rare Disease and Birth Defects Unit, Department of Woman, Child Health and Public Health, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.

Pregnancy after bariatric surgery is usually considered safe. Recently, a few studies reported that bariatric surgery represents a risk factor for birth defects. A case series of six patients, born from women who had undergone biliopancreatic diversion, is reported. The clinical pattern was characterized by psychomotor development delay (100%), microphthalmia (83%), growth retardation (66%), hearing loss (66%), and variable facial dysmorphism. Based on the clinical profile and symptoms reported by women during pregnancy, a causal association between maternal chronic post-surgical malabsorption, congenital anomalies, and neonatal outcome is proposed, with vitamin A deficiency representing a major causing factor. Educational follow-up support, continuous clinical monitoring, and appropriate nutritional assessment appear to be crucial to reduce the potential risk of congenital malformations and child disability.
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http://dx.doi.org/10.1007/s11695-020-04882-wDOI Listing
January 2021

A novel IRF2BPL truncating variant is associated with endolysosomal storage.

Mol Biol Rep 2020 Jan 3;47(1):711-714. Epub 2019 Oct 3.

Department of Molecular Medicine, University of Pavia, via Forlanini 14, 27100, Pavia, Italy.

De novo mutations in the IRF2BPL gene have been identified to date in 18 patients presenting with neuromotor regression, epilepsy and variable neurological signs. Here, we report a female child carrying a novel heterozygous truncating variant in IRF2BPL. Following normal development for two and half years, she developed a progressive neurological condition with psychomotor regression, dystonic tetraparesis with hyperkinetic movements, but no overt epilepsy. Skin biopsy revealed enlarged lysosomes containing granular and tubular material, suggestive of a lysosomal storage disorder. This case expands the IRF2BPL phenotypic spectrum, for the first time providing evidence of endolysosomal storage.
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http://dx.doi.org/10.1007/s11033-019-05109-7DOI Listing
January 2020

Clinical features and genetic analysis of two siblings with startle disease in an Italian family: a case report.

BMC Med Genet 2019 03 12;20(1):40. Epub 2019 Mar 12.

Child Neurology and Psychiatry, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

Background: Hyperekplexia also known as Startle disease is a rare neuromotor hereditary disorder characterized by exaggerated startle responses to unexpected auditory, tactile, and visual stimuli and generalized muscle stiffness, which both gradually subside during the first months of life. Although the diagnosis of Hyperekplexia is based on clinical findings, pathogenic variants in five genes have been reported to cause Hyperekplexia, of which GLRA1 accounts for about 80% of cases. Dominant and recessive mutations have been identified in GLRA1 gene as pathogenic variants in many individuals with the familial form of Hyperekplexia and occasionally in simplex cases.

Case Presentation: In the present study, we describe clinical and genetic features of two Italian siblings, one with the major and one with the minor form of the disease. DNA samples from the probands and their parents were performed by NGS approach and validated by Sanger sequencing. The analysis of the GLRA1 gene revealed, in both probands, compound heterozygous mutations: c.895C > T or p.R299X inherited from the mother and c.587C > A or p.D98E inherited from the father.

Conclusions: Until now, these two identified mutations in GLRA1 have not been reported before as compound mutations. What clearly emerges within our study is the clinical heterogeneity in the same family. In fact, even though in the same pedigree, the affected mother showed only mild startle responses to unexpected noise stimuli, which might be explained by variable expressivity, while the father, showed no clear signs of symptomatology, which might be explained by non-penetrance. Finally, the two brothers have different form of the disease, even if the compound heterozygous mutations in GLRA1 are the same, showing that the same mutation in GLRA1 could have different phenotypic expressions and suggesting an underling mechanism of variable expressivity.
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http://dx.doi.org/10.1186/s12881-019-0779-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417078PMC
March 2019

Syndromic Craniosynostosis Can Define New Candidate Genes for Suture Development or Result from the Non-specifc Effects of Pleiotropic Genes: Rasopathies and Chromatinopathies as Examples.

Front Neurosci 2017 18;11:587. Epub 2017 Oct 18.

Institute of Genomic Medicine, Catholic University, A. Gemelli Hospital, Rome, Italy.

Craniosynostosis is a heterogeneous condition caused by the premature fusion of cranial sutures, occurring mostly as an isolated anomaly. Pathogenesis of non-syndromic forms of craniosynostosis is largely unknown. In about 15-30% of cases craniosynostosis occurs in association with other physical anomalies and it is referred to as syndromic craniosynostosis. Syndromic forms of craniosynostosis arise from mutations in genes belonging to the Fibroblast Growth Factor Receptor (FGFR) family and the interconnected molecular pathways in most cases. However it can occur in association with other gene variants and with a variety of chromosome abnormalities as well, usually in association with intellectual disability (ID) and additional physical anomalies. Evaluating the molecular properties of the genes undergoing intragenic mutations or copy number variations (CNVs) along with prevalence of craniosynostosis in different conditions and animal models if available, we made an attempt to define two distinct groups of unusual syndromic craniosynostosis, which can reflect direct effects of emerging new candidate genes with roles in suture homeostasis or a non-specific phenotypic manifestation of pleiotropic genes, respectively. RASopathies and 9p23p22.3 deletions are reviewed as examples of conditions in the first group. In particular, we found that craniosynostosis is a relatively common component manifestation of cardio-facio-cutaneous (CFC) syndrome. Chromatinopathies and neurocristopathies are presented as examples of conditions in the second group. We observed that craniosynostosis is uncommon on average in these conditions. It was randomly associated with Kabuki, Koolen-de Vries/ haploinsufficiency and Mowat-Wilson syndromes and in -related disorders. As an exception, trigonocephaly in Bohring-Opitz syndrome reflects specific molecular properties of the chromatin modifier gene. Surveillance for craniosynostosis in syndromic forms of intellectual disability, as well as ascertainment of genomic CNVs by array-CGH in apparently non-syndromic craniosynostosis is recommended, to allow for improvement of both the clinical outcome of patients and the accurate individual diagnosis.
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http://dx.doi.org/10.3389/fnins.2017.00587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651252PMC
October 2017

Intravenous immunoglobulin for Pediatric Neuropsychiatric Lupus Triggered by Epstein-Barr Virus Cerebral Infection.

Isr Med Assoc J 2016 Dec;18(12):763-766

Department of Pediatric Neurology, Catholic University, Gemelli Hospital, Rome, Italy.

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December 2016

Clinical and genetic factors predicting Dravet syndrome in infants with mutations.

Neurology 2017 Mar 15;88(11):1037-1044. Epub 2017 Feb 15.

From the Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories (V.C., S.C., D.M., E.P., C.M., D.P., R.G.), Neuroscience Department, A Meyer Children's Hospital, University of Florence; Department of Statistics, Computer Science and Applications (L.G.), University of Florence; Division of Child Neurology and Psychiatry Epilepsy and Clinical Neurophysiology Laboratory (A.F., F.S., R.G.), IRCCS Stella Maris Foundation, Pisa; Department of Neurosciences (N.S., M.T.), Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome; Child Neuropsichiatry Fondazione Policlinico Universitario Agostino Gemelli (D.B., I.C.), Università Cattolica del Sacro Cuore, Rome; Child Neuropsychiatry Unit (N.Z., C.P.), Ospedali Riuniti, Ancona; and Department of Pediatric Neuroscience (T.G., F.R., G.A.), Foundation IRCCS Neurological Institute C. Besta, Milan, Italy.

Objective: To explore the prognostic value of initial clinical and mutational findings in infants with mutations.

Methods: Combining sex, age/fever at first seizure, family history of epilepsy, EEG, and mutation type, we analyzed the accuracy of significant associations in predicting Dravet syndrome vs milder outcomes in 182 mutation carriers ascertained after seizure onset. To assess the diagnostic accuracy of all parameters, we calculated sensitivity, specificity, receiver operating characteristic (ROC) curves, diagnostic odds ratios, and positive and negative predictive values and the accuracy of combined information. We also included in the study demographic and mutational data of the healthy relatives of mutation carrier patients.

Results: Ninety-seven individuals (48.5%) had Dravet syndrome, 49 (23.8%) had generalized/genetic epilepsy with febrile seizures plus, 30 (14.8%) had febrile seizures, 6 (3.5%) had focal epilepsy, and 18 (8.9%) were healthy relatives. The association study indicated that age at first seizure and frameshift mutations were associated with Dravet syndrome. The risk of Dravet syndrome was 85% in the 0- to 6-month group, 51% in the 6- to 12-month range, and 0% after the 12th month. ROC analysis identified onset within the sixth month as the diagnostic cutoff for progression to Dravet syndrome (sensitivity = 83.3%, specificity = 76.6%).

Conclusions: In individuals with mutations, age at seizure onset appears to predict outcome better than mutation type. Because outcome is not predetermined by genetic factors only, early recognition and treatment that mitigates prolonged/repeated seizures in the first year of life might also limit the progression to epileptic encephalopathy.
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http://dx.doi.org/10.1212/WNL.0000000000003716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384833PMC
March 2017

Cognitive-behavioral profiles in teenagers with Dravet syndrome.

Brain Dev 2016 Jun 18;38(6):554-62. Epub 2016 Jan 18.

Child Neurology and Psychiatry, Catholic University, Rome, Italy. Electronic address:

Aim: To investigate behavior and cognitive performances of teenage patients with Dravet syndrome (DS).

Methods: We enrolled 20 teenage patients (12 females and 8 males) with DS, followed in the Child Neurology Unit of the Catholic University (Rome). Patients underwent a full clinical examination including behavioral and cognitive assessments (respectively, CBCL and Wechsler scales).

Results: All patients showed behavior disorders and mental retardation, mild in six cases, moderate in seven and severe in the remaining seven. Among mildly retarded patients visual function, particularly visuo-motor abilities resulted mostly impaired in Wechsler subtests, whereas verbal skills were relatively preserved. In contrast, a general cognitive impairment was observed in moderately and severely retarded patients.

Conclusions: Our teenage patients with DS compared with other series at different ages (young childhood, adulthood) suggest a progressivity of neurological and neuropsychological signs. A visuomotor default and a relative preservation of verbal skills, like what has been found in previous reports of younger patients, are still evident in mildly impaired cases. Therefore, the progression over time of these cases toward a generalized impairment may be suggested, but only longitudinal studies can confirm it. There was a possible responsibility of some epileptic disorders in worsening the neuropsychological outcome (early myoclonic seizures and atypical absences, as well as persistent EEG background slowness in the last 3years).
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http://dx.doi.org/10.1016/j.braindev.2015.12.014DOI Listing
June 2016

Intragenic KANSL1 mutations and chromosome 17q21.31 deletions: broadening the clinical spectrum and genotype-phenotype correlations in a large cohort of patients.

J Med Genet 2015 Dec 30;52(12):804-14. Epub 2015 Sep 30.

Division of Clinical Genetics, Children's Hospital of Philadelphia, Philadelphia, USA.

Background: The 17q21.31 deletion syndrome phenotype can be caused by either chromosome deletions or point mutations in the KANSL1 gene. To date, about 60 subjects with chromosome deletion and 4 subjects with point mutation in KANSL1 have been reported. Prevalence of chromosome deletions compared with point mutations, genotype-phenotype correlations and phenotypic variability have yet to be fully clarified.

Methods: We report genotype-phenotype correlations in 27 novel subjects with 17q21.31 deletion and in 5 subjects with KANSL1 point mutation, 3 of whom were not previously reported.

Results: The prevalence of chromosome deletion and KANSL1 mutation was 83% and 17%, respectively. All patients had similar clinical features, with the exception of macrocephaly, which was detected in 24% of patients with the deletion and 60% of those with the point mutation, and congenital heart disease, which was limited to 35% of patients with the deletion. A remarkable phenotypic variability was observed in both categories, mainly with respect to the severity of ID. Cognitive function was within normal parameters in one patient in each group. Craniosynostosis, subependymal heterotopia and optic nerve hypoplasia represent new component manifestations.

Conclusions: In KANSL1 haploinsufficiency syndrome, chromosome deletions are greatly prevalent compared with KANSL1 mutations. The latter are sufficient in causing the full clinical phenotype. The degree of intellectual disability (ID) appears to be milder than expected in a considerable number of subjects with either chromosome deletion or KANSL1 mutation. Striking clinical criteria for enrolling patients into KANSL1 analysis include speech delay, distinctive facial dysmorphism, macrocephaly and friendly behaviour.
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http://dx.doi.org/10.1136/jmedgenet-2015-103184DOI Listing
December 2015

Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome.

Eur J Hum Genet 2015 Nov 25;23(11):1499-504. Epub 2015 Feb 25.

Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Roma, Italy.

MED13L haploinsufficiency has recently been described as responsible for syndromic intellectual disability. We planned a search for causative gene variants in seven subjects with intellectual disability and overlapping dysmorphic facial features such as bulbous nasal tip, short mouth and straight eyebrows. We found two de novo frameshift variants in MED13L, consisting in single-nucleotide deletion (c.3765delC) and duplication (c.607dupT). A de novo nonsense variant (c.4420A>T) in MED13L was detected in a further subject in the course of routine whole-exome sequencing. By analyzing the clinical data of our patients along with those recently described in the literature, we confirm that there is a common, recognizable phenotype associated with MED13L haploinsufficiency, which includes intellectual disability and a distinctive facial appearance. Congenital heart diseases are found in some subjects with various degree of severity. Our observation of cleft palate, ataxia, epilepsy and childhood leukemia observed in single cases broadens the known clinical spectrum. Haploinsufficiency for MED13L should be considered in the differential diagnosis of the 1p36 microdeletion syndrome, due to overlapping dysmorphic facial features in some patients. The introduction of massive parallel-sequencing techniques into clinical practice is expected to allow for detection of other causative point variants in MED13L. Analysis of genomic data in connection with deep clinical evaluation of patients could elucidate genetic heterogeneity of the MED13L haploinsufficiency phenotype.
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http://dx.doi.org/10.1038/ejhg.2015.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613466PMC
November 2015

Sleep-potentiated epileptiform activity in early thalamic injuries: Study in a large series (60 cases).

Epilepsy Res 2015 Jan 28;109:90-9. Epub 2014 Oct 28.

Child Neurology and Psychiatry, Catholic University, Rome, Italy. Electronic address:

Objective: The study aims at a better definition of continuous spike-waves during sleep (CSWS) with an early thalamic lesion, focusing on various grades of sleep-potentiated epileptiform activity (SPEA). Their possible relationship with different clinical features was studied to try to define prognostic factors of the epileptic disorder, especially relating to behavior/cognitive outcome, in order to improve prevention and treatment strategies.

Methods: Sixty patients with early thalamic injury were followed since the first registration of SPEA with serial neurological, long term EEG monitoring and neuropsychological examinations, as well as neuroimaging and a detailed clinical history. They were classified in three different groups according to the sleep spike-waves (SW) quantification: electrical status epilepticus during sleep (ESES), more than 85% of slow sleep; overactivation between 50% and 85% and simple activation between 10 and 50%). Results were then examined also with a statistical analysis.

Results: In our series of CSWS occurring in early brain injured children with unilateral thalamic involvement there is a common neuropathologic origin but with various grades of SPEA severity. Statistical analysis showed that patients evolving toward ESES presented more commonly the involvement of the mediodorsal part of thalamus nuclei and a bilateral cortico-subcortical brain injury, epilepsy was more severe with a delayed onset; moreover, in the acute stage .ESES patients presented the worst behavior/cognitive performances. As to cognitive and behavior outcome, longer SPEA duration as well as bilateral brain injury and cognitive/behavior impairment in acute phase appear linked to a poor outcome; some particular neuropathology (ischemic stroke and haemorrhagic infarction) as well as hydrocephalus shunting are associated with behavior disorders.

Conclusions: Discrete features seem to support different underlying mechanisms in ESES patients in comparison with less severe SPEA; they represent negative prognostic factors. Longer SPEA duration as well as bilateral brain injury and cognitive/behavior impairment in acute phase seem predictive of a worse cognitive/behavior outcome.
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http://dx.doi.org/10.1016/j.eplepsyres.2014.10.015DOI Listing
January 2015

Unusual 4p16.3 deletions suggest an additional chromosome region for the Wolf-Hirschhorn syndrome-associated seizures disorder.

Epilepsia 2014 Jun 16;55(6):849-57. Epub 2014 Apr 16.

Institute of Medical Genetics, Catholic University, University Hospital A. Gemelli, Roma, Italy.

Objective: Seizure disorder is one of the most relevant clinical manifestations in Wolf-Hirschhorn syndrome (WHS) and it acts as independent prognostic factor for the severity of intellectual disability (ID). LETM1, encoding a mitochondrial protein playing a role in K(+) /H(+) exchange and in Ca(2+) homeostasis, is currently considered the major candidate gene. However, whether haploinsufficiency limited to LETM1 is enough to cause epilepsy is still unclear. The main purpose of the present research is to define the 4p chromosome regions where genes for seizures reside.

Methods: Comparison of our three unusual 4p16.3 deletions with 13 literature reports. Array-comparative genomic hybridization (a-CGH). Real-time polymerase chain reaction (RT-PCR) on messanger RNA (mRNA) of LETM1 and CPLX1. Direct sequencing of LETM1.

Results: Three unusual 4p16.3 deletions were detected by array-CGH in absence of a obvious clinical diagnosis of WHS. Two of these, encompassing LETM1, were found in subjects who never had seizures. The deletions were interstitial, spanning 1.1 Mb with preservation of the terminal 1.77 Mb region in one case and 0.84 Mb with preservation of the terminal 1.07 Mb region in the other. The other deletion was terminal, affecting a 0.564 Mb segment, with preservation of LETM1, and it was associated with seizures and learning difficulties. Upon evaluating our patients along with literature reports, we noted that six of eight subjects with terminal 4p deletions preserving LETM1 had seizures, whereas seven of seven with interstitial deletions including LETM1 and preserving the terminal 1 Mb region on 4p did not. An additional chromosome region for seizures is suggested, falling within the terminal 1.5 Mb on 4p, not including LETM1.

Significance: We consider that haploinsufficiency not limited to LETM1 but including other genes acts as a risk factor for the WHS-associated seizure disorder, according to a comorbidity model of pathogenesis. Additional candidate genes reside in the terminal 1.5 Mb region on 4p, most likely distal to LETM1. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
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http://dx.doi.org/10.1111/epi.12617DOI Listing
June 2014

Cognitive decline in Dravet syndrome: is there a cerebellar role?

Epilepsy Res 2013 Sep 30;106(1-2):211-21. Epub 2013 Apr 30.

Child Neurology and Psychiatry, Catholic University, Rome, Italy.

Purpose: The aim of the study was to perform a detailed assessment of cognitive abilities and behaviour in a series of epileptic patients with Dravet syndrome (DS) in order to establish a possible cerebellar-like pattern.

Methods: Nine children with DS without major behavioural disturbances and with cognitive abilities compatible with the assessment of specific cognitive skills (IQ>45) were enrolled in the study, in parallel with another group of nine epileptic patients (cryptogenic or symptomatic with minor brain injuries) consecutively admitted into the hospital matched for chronological age and IQ. All cases underwent neurological examination, long term EEG monitoring, neuroimaging and genetic analysis as well as a neuropsychological assessment including specific cognitive skills.

Results: On neurological examination 8 of the 9 DS patients had cerebellar signs, which were mild in six and more severe in the other two cases. DS patients had a constant discrepancy between verbal and performance items scales (verbal better than visual-spatial) that was not found in the control group. As to specific cognitive competence, the DS patients differ from the control group in the pattern of cognitive defects involving four main areas of cognitive abilities (a) expressive language with relatively spared comprehension, (b) visual-spatial organization, (c) executive function defects, (d) behavioural disorders.

Cunclusions: The pattern of cognitive difficulties found in DS patients is consistent with what is reported in literature as cerebellar cognitive syndrome and may account for a possible cerebellar origin (at least as co-factor) of the cognitive decline observed in DS patients, as suggested by other clinical and experimental studies.
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http://dx.doi.org/10.1016/j.eplepsyres.2013.03.012DOI Listing
September 2013

The forward parachute reaction and independent walking in infants with brain lesions.

Dev Med Child Neurol 2011 Jul 21;53(7):636-40. Epub 2011 Mar 21.

Paediatric Neurology Unit, Catholic University, Rome, Italy.

Aim: The aim of this study was to assess the onset of forward parachute reaction (FPR) in infants with brain lesions and its correlation with age of walking.

Method: FPR was assessed at 6, 9, and 12 months in 140 infants with brain lesions (78 males, 62 females; mean gestational age 31 wks; SD 3.6 wks; mean birthweight 1450 g, SD 252 g). On cranial ultrasound 62 infants had mild and 78 had major abnormalities; 86 developed cerebral palsy. All were followed for 5 years, and the age at which each child achieved independent walking was recorded. Infants who had been born small for gestational age (weight <10th centile) were excluded, as were those who had major congenital malformations, severe postnatal infectious diseases, or metabolic or haematological complications.

Results: A complete FPR was present in eight infants at 6 months, in 42 at 9 months, and in 71 at 12 months. At 12 months, 29 infants presented incomplete FPR and 40 presented absent FPR. Seventy-three infants were able to walk independently between the ages of 11 months and 60 months (67 with complete FPR and six with incomplete FPR at 12 mo). A complete FPR at 12 months was a good predictor of independent walking. The age at onset of complete FPR was also a good predictor of age of walking.

Interpretation: The late acquisition of a complete FPR appears to be an early sign of a more general delayed maturation of functional abilities.
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http://dx.doi.org/10.1111/j.1469-8749.2011.03940.xDOI Listing
July 2011

Early visual assessment in preterm infants with and without brain lesions: correlation with visual and neurodevelopmental outcome at 12 months.

Early Hum Dev 2011 Mar 14;87(3):177-82. Epub 2011 Jan 14.

Paediatric Neurology Unit, Catholic University, Rome, Italy.

Background: Several studies have reported the development of various aspects of visual function in infancy and early childhood in both preterm and term-born infants, but only a few studies have focused on the predictive power of neonatal visual findings in infants with brain lesions.

Aims: To explore visual findings at term age, and at 3 and 12 months corrected age in preterm infants (gestational age <33 weeks) with and without brain lesions; to compare the assessment at term age and at 12 months; and to assess the relationship between visual findings and neurodevelopmental outcome at 12 months.

Study Design: Cranial ultrasound scans (US) were classified in normal, mild or major abnormalities. One-hundred and forty-five infants were assessed with age specific tests for visual function at term age, and at 3 and 12 months. Neurodevelopmental assessment (Griffiths' Scales) was performed at 12 months.

Results: A good correlation was found between early and late visual assessment and neurodevelopment outcome. Of the 121 infants with normal neonatal visual assessment, 119 were also normal at 12 months and 116 had normal developmental quotient. Of the 24 infants with abnormal neonatal visual assessment, 12 were also abnormal at 12 months. All the false positives had normalised by 3 months. Of the 35 infants with major US abnormalities, 20 had normal and 15 abnormal scores on the neonatal assessment. At 1 year 17 had normal and 18 abnormal scores.

Conclusion: A normal visual assessment at term age is a good predictor of normal visual and neurodevelopmental outcome at 12 months. An abnormal visual examination in the neonatal period was a less reliable prognostic indicator, infant should be reassessed at 3 months.
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http://dx.doi.org/10.1016/j.earlhumdev.2010.12.003DOI Listing
March 2011

Surgery of children with frontal lobe lesional epilepsy: neuropsychological study.

Brain Dev 2011 Apr 5;33(4):310-5. Epub 2010 Nov 5.

Child Neurology and Psychiatry Unit, Catholic University, Largo Gemelli 8, Rome, Italy.

Aim Of The Study: was to provide new data about the evolution of neuropsychological findings in patients with lesional frontal lobe epilepsy (FLE) operated on with lesion excision.

Patients And Methods: Twelve patients with lesional FLE underwent full clinical examination including neurological, neuropsychological and developmental assessments, high-resolution magnetic resonance imaging (MRI), ictal and interictal prolonged EEG monitoring and evaluation of seizure semeiology before and after surgery. The mean follow-up duration was 2 years and 10 months (range=14 months-7 years). Another group of lesional temporal lobe epilepsy, matched for the age at surgery and side of surgery, was likewise studied in order to compare neuropsychological patterns and to try to find out specific features in frontal lobe epilepsy evolution.

Results: All patients resulted seizure free at outcome except one belonging to Engel's class II. Before surgery general intelligence was similar in FLE as well as in TLE group. Executive functions and motor coordination were frequently affected in FLE whereas patients with TLE often presented with deficits in naming, visual memory and visuo-spatial attention. After surgery there was a frequent decline of IQ in FLE group together with a slight deterioration, especially of executive functions in some patients. An improvement of behaviour was often observed in both groups.

Conclusions: As already reported in literature, neuropsychological pre-surgical data confirms the involvement of attention and executive functions in lesional FLE. No significant neuropsychological improvement was produced by surgery that determined in some cases a slight decline of general intelligence and specific frontal abilities. Yet, generally behaviour improved and seizures were controlled.
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http://dx.doi.org/10.1016/j.braindev.2010.06.006DOI Listing
April 2011

Early onset myoclonic epilepsy and 15q26 microdeletion: observation of the first case.

Epilepsia 2009 Jul 19;50(7):1810-5. Epub 2009 Apr 19.

Child Neurology and Psychiatry, Catholic University, Rome, Italy.

The authors report the study of a 30-month-old girl with refractory myoclonic epilepsy associated with mental retardation, growth delay, peculiar facial appearance, and minor physical anomalies. Extensive genetic studies were performed, including an array-based comparative genomic hybridization (array-CGH) that showed a cryptic interstitial deletion of 15q (5 Mb) affecting the 15q26.1-26.2 region. Partial deletions of the long arm of chromosome 15, including the 15q26 region, were observed in syndromic associations that typically include congenital diaphragmatic hernia, but neurologic features were poorly described and epileptic seizures were never reported. Our findings suggest that genes for seizures could be included in the 15q26.1q26.2 deletion interval.
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http://dx.doi.org/10.1111/j.1528-1167.2009.02078.xDOI Listing
July 2009

Longstanding epileptic encephalopathy and linear localized scleroderma: two distinct pathologic processes in an adolescent.

Rheumatol Int 2008 Jul 16;28(9):925-9. Epub 2008 Feb 16.

Center of Periodic Fevers, Department of Pediatric Sciences, Università Cattolica Sacro Cuore, Largo A. Gemelli no. 8, 00168, Rome, Italy.

We report a 7-year-old boy who unexpectedly developed a multi-drug resistant epilepsy with negative neuroimaging results, followed by the insidious appearance of linear localized scleroderma involving the right leg. When the boy was 16 and severely affected by epileptic encephalopathy, we have evaluated this case for the first time: his localized scleroderma had reached the right buttock and positive anti-nuclear antibody was the only positive laboratory test. Methotrexate administered for 12 months was ineffective in improving both the organization of his electroencephalographic pattern and seizure control, though seemed to stabilize the progression of linear scleroderma. This report suggests that neurological abnormality and extracranial scleroderma might represent two own distinct processes in a same patient.
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http://dx.doi.org/10.1007/s00296-008-0541-8DOI Listing
July 2008
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