Bianciardi G.,University of Siena |
Lamberti I.,Emergenza Territoriale |
Sartini S.,University of Siena |
Servi M.,Medicina Generale |
And 3 more authors.
Clinical Hemorheology and Microcirculation | Year: 2013
Rett syndrome (RTT) is a post-natal neurological disorder that represents the second most common cause for mental retardation. The presence of cold hands and feet, and blue, a feature frequently observed in these patients, is one of the non-neurological phenotypes that characterizes RTT, up to now not well explained. We have performed videocapillaroscopy in subjects affected by Rett syndrome. We have observed ramified and bushy capillaries, characteristic features of neoangiogenic capillaries, dilated capillaries and an irregular and chaotic microvascular pattern. To quantify these features and to evaluate the microvascular pattern complexity, we have performed a fractal analysis. Fractal dimension and Lempel-Ziv indexes resulted higher in Rett females than in age-matched healthy females (p < 0.001; p < 0.001). Our findings indicate the presence of previously unrecognized microvascular abnormalities in Rett syndrome. © 2013 - IOS Press and the authors. All rights reserved.
Marangi G.,Catholic University of the Sacred Heart |
Ricciardi S.,Catholic University of the Sacred Heart |
Orteschi D.,Catholic University of the Sacred Heart |
Lattante S.,Catholic University of the Sacred Heart |
And 21 more authors.
American Journal of Medical Genetics, Part A | Year: 2011
Pitt-Hopkins syndrome (PTHS) is characterized by severe intellectual disability, typical facial gestalt and additional features, such as breathing anomalies. Following the discovery of the causative haploinsufficiency of transcription factor 4 (TCF4), about 60 patients have been reported. We looked for TCF4 mutations in 63 patients with a suspected PTHS. Haploinsufficiency of TCF4 was identified in 14 patients, as a consequence of large 18q21.2 chromosome deletions involving TCF4 (2 patients), gene mutations (11 patients) and a t(14q;18q) balanced translocation disrupting TCF4 (one patient). By evaluating the clinical features of these patients, along with literature data, we noticed that, in addition to the typical facial gestalt, the PTHS phenotype results from the various combinations of the following characteristics: intellectual disability with severe speech impairment, normal growth parameters at birth, postnatal microcephaly, breathing anomalies, motor incoordination, ocular anomalies, constipation, seizures, typical behavior and subtle brain abnormalities. Although PTHS is currently considered to be involved in differential diagnosis with Angelman and Rett syndromes, we found that combining the facial characteristics with a detailed analysis of both the physical and the neurological phenotype, made molecular testing for PTHS the first choice. Based on striking clinical criteria, a diagnosis of PTHS was made clinically in two patients who had normal TCF4. This report deals with the first series of PTHS patients of Italian origin. © 2011 Wiley-Liss, Inc.
Novara F.,University of Pavia |
Beri S.,Biologia Molecolare |
Giorda R.,Biologia Molecolare |
Nageshappa S.,University Hospitals Leuven |
And 4 more authors.
Clinical Genetics | Year: 2010
Novara F, Beri S, Giorda R, Ortibus E, Nageshappa S, Darra F, dalla Bernardina B, Zuffardi O, Van Esch H. Refining the phenotype associated with MEF2C haploinsufficiency.Recently, submicroscopic deletions of the 5q14.3 region have been described in patients with severe mental retardation (MR), stereotypic movements, epilepsy and cerebral malformations. Further delineation of a critical region of overlap in these patients pointed to MEF2C as the responsible gene. This finding was further reinforced by the identification of a nonsense mutation in a patient with a similar phenotype. In brain, MEF2C is essential for early neurogenesis, neuronal migration and differentiation. Here we present two additional patients with severe MR, autism spectrum disorder and epilepsy, carrying a very small deletion encompassing the MEF2C gene. This finding strengthens the role of this gene in severe MR, and enables further delineation of the clinical phenotype. © 2010 John Wiley & Sons A/S.
Caraballo R.H.,Hospital Of Pediatria Prof Dr Juan P Garrahan |
Chamorro N.,Hospital Of Pediatria Prof Dr Juan P Garrahan |
Darra F.,Neuropsichiatria Infantile |
Fortini S.,Hospital Of Pediatria Prof Dr Juan P Garrahan |
Arroyo H.,Hospital Of Pediatria Prof Dr Juan P Garrahan
Pediatric Neurology | Year: 2013
Epilepsy with myoclonic-atonic seizures is characterized by myoclonic-atonic, absence, tonic-clonic, and eventually tonic seizures, appearing in previously normal children at ages 18-60 months. We analyzed the electroclinical features, treatment, and outcome of 69 patients with myoclonic-atonic seizures; these patients were followed between 1990 and 2012 at the Juan P. Garrahan Pediatric Hospital, Buenos Aires, Argentina. No structural or metabolic etiology was identified. Based on the electroclinical features and evolution, two groups could be distinguished. The first group of 39 patients with myoclonic and myoclonic-atonic seizures with or without generalized tonic-clonic seizures and absences associated with generalized spike- and polyspike-and-wave paroxysms had excellent prognoses. The second group of 30 patients had myoclonic jerks and myoclonic-atonic seizures associated with other seizure types including tonic seizures; some had myoclonic status epilepticus and cognitive deterioration. The interictal EEG showed frequent generalized spike- and polyspike-and-wave paroxysms. In 16 patients, the seizures remitted within 3.6 years. The two groups were distinguished in retrospect, when enough time had elapsed to evaluate cognitive deterioration and different seizure types. In conclusion, epilepsy with myoclonic atonic seizures is an epileptic syndrome with a broad clinical spectrum and variable prognosis. © 2013 Elsevier Inc. All rights reserved.
Giordano L.,Centro Regionale Epilessia |
Vignoli A.,University of Milan |
Accorsi P.,Centro Regionale Epilessia |
Galli J.,University of Milan |
And 21 more authors.
Epilepsy Research | Year: 2011
Purpose: To investigate the electroclinical features and the outcome of patients with typical absences starting before the 3 years of life. Methods: We reviewed the clinical data of patients with absences started before 3 years observed over a 15-year period. Mutation analysis of SLC2A1 (GLUT-1) gene was performed when possible. Their clinical features were compared with those of subjects with a diagnosis of childhood absence epilepsy (CAE). Results: Among 33 children with absence epilepsy starting before 3 years of life, there were 20 boys and 13 girls. Mean seizure onset was at 28.0 ± 8.3 (range: 8-36) months of life. Two children displayed borderline intellectual functioning at long-term follow-up. Twenty-eight (85%) patients showed excellent response to therapy. Three subjects evolved into a different form of idiopathic generalized epilepsy (IGE). No SLC2A1 mutation was identified in 20 (60.6%) patients tested.The main clinical features of patients with early-onset absences did not differ from those of CAE except for increased prevalence of males (p=0.002) and longer treatment duration (p=0.001) in the former. Conclusions: Strong similarities in the electroclinical features and outcome between children with early-onset absences and those with CAE support the view that these conditions are part of the wide spectrum of IGE. © 2011 Elsevier B.V.
PubMed | The Hospital for Sick Children, Hospital for Sick Children, Genetica Medica, Memorial University of Newfoundland and 6 more.
Type: Case Reports | Journal: Journal of medical genetics | Year: 2015
Deadenylation regulates RNA function and fate. Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA. Little is known about the biological significance of germline mutations in PARN.We identified mutations in PARN in patients with haematological and neurological manifestations. Genomic, biochemical and knockdown experiments in human marrow cells and in zebrafish have been performed to clarify the role of PARN in the human disease.We identified large monoallelic deletions in PARN in four patients with developmental delay or mental illness. One patient in particular had a severe neurological phenotype, central hypomyelination and bone marrow failure. This patient had an additional missense mutation on the non-deleted allele and severely reduced PARN protein and deadenylation activity. Cells from this patient had impaired oligoadenylation of specific H/ACA box small nucleolar RNAs. Importantly, PARN-deficient patient cells manifested short telomeres and an aberrant ribosome profile similar to those described in some variants of dyskeratosis congenita. Knocking down PARN in human marrow cells and zebrafish impaired haematopoiesis, providing further evidence for a causal link with the human disease.Large monoallelic mutations of PARN can cause developmental/mental illness. Biallelic PARN mutations cause severe bone marrow failure and central hypomyelination.
Colonna F.,Science di Pediatria |
Moretto E.,Science di Pediatria |
Costa P.,Neuropsichiatria Infantile |
Zennaro F.,Radiologia A Indirizzo Pediatrico
Medico e Bambino | Year: 2011
An 11-month-old female was admitted to our hospital for anorexia, pallor and developmental regression. She had been exclusively breast-fed. Mother with thyroiditis, non vegetarian. Hemogram in the baby revealed macrocytic anaemia (8.4 g/dl Hb, MCV 99); serum folate level was normal, cobalamine level not measurable. Subsequently, cobalamine deficiency and autoimmune gastritis were diagnosed in her mother. Cerebral NMR revealed fronto-temporal subatrophy. Intramuscular cobalamine injections in daily dose of 1,000 μg were given. After few days of treatment, involuntary movements appeared (controlled by clonazepam). Later, favourable clinical course and slow but progressive improvement of neurological development were observed. Seven months later, serum haemoglobin and cobalamine level were normal and cerebral NMR almost completely normalized. We remark the importance of macrocytosis in the diagnosis of cobalamine deficiency.
PubMed | Neuropsichiatria Infantile
Type: Journal Article | Journal: Cephalalgia : an international journal of headache | Year: 2011
This study aimed to evaluate the presence of pressure-painful scalp arteries in children and adolescents with migraine.Pressure-painful points on scalp arteries were searched in 130 consecutive children (6-12 years old) and adolescents (>13 years old) affected with migraine, 89 females and 41 males, and in 40 age-matched controls.In the absence of a migraine episode, we examined 76 patients: 54 (71.1%) reported one or more pressure-painful arteries and 22 reported none. Of the 40 controls, pressure-painful arteries were present in 11, with a highly significant difference (p<0.0001). During a migraine attack, of the 54 patients examined, 43 (79.6 %) reported one or more pressure-painful arteries and 11 reported none. The arteries most frequently painful were the frontal branch and the superficial temporal artery.Scalp arteries are frequently painful on pressure in children and adolescents with migraine, both in the absence of and during a migraine attack. Painful arteries suggest hypersensitivity of periarterial nociceptive afferents.
Giovannini S.,Neuropsichiatria Infantile |
Frattini D.,Neuropsichiatria Infantile |
Scarano A.,Neuropsichiatria Infantile |
Fusco C.,Neuropsichiatria Infantile |
And 7 more authors.
Epileptic Disorders | Year: 2010
Epilepsy is the most common and serious neurological symptom in ring chromosome 14 syndrome, also characterised by mild dysmorphisms, acquired microcephaly, cognitive impairment, hypotonia and ocular abnormalities. Typically, early-onset, polymorphous and drug-resistant seizures are reported. Status epilepticus has not been previously reported. We describe a nine-year-old Caucasian boy with ring 14 syndrome who presented a severe early-onset and drug-resistant focal epilepsy with secondary generalised seizures and repetitive episodes of convulsive and non-convulsive status epilepticus. The electro-clinical evaluation of prolonged seizures and their long-term consequences is important for the practical management of these patients and for a better comprehension of the syndrome. © 2010 John Libbey Eurotext and Springer.
PubMed | Neuropsichiatria Infantile
Type: Case Reports | Journal: Epileptic disorders : international epilepsy journal with videotape | Year: 2010
Epilepsy is the most common and serious neurological symptom in ring chromosome 14 syndrome, also characterised by mild dysmorphisms, acquired microcephaly, cognitive impairment, hypotonia and ocular abnormalities. Typically, early-onset, polymorphous and drug-resistant seizures are reported. Status epilepticus has not been previously reported. We describe a nine-year-old Caucasian boy with ring 14 syndrome who presented a severe early-onset and drug-resistant focal epilepsy with secondary generalised seizures and repetitive episodes of convulsive and non-convulsive status epilepticus. The electro-clinical evaluation of prolonged seizures and their long-term consequences is important for the practical management of these patients and for a better comprehension of the syndrome.