Mutation spectrum of NF1 gene in Italian patients with neurofibromatosis type 1 using Ion Torrent PGM™ platform.

Neurofibromatosis type 1 (NF1) is caused by mutations of the NF1 gene and is one of the most common human autosomal dominant disorders. The patient shows different signs on the skin and other organs from early childhood. The best known are six or more café au lait spots, axillary or inguinal freckling, increased risk of developing benign nerve sheath tumours and plexiform neurofibromas.

Cognitive, adaptive, and behavioral features in Joubert syndrome.

Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by a distinctive cerebellar and brainstem malformation recognizable on brain imaging, the so-called molar tooth sign. The full spectrum of cognitive and behavioral phenotypes typical of JS is still far from being elucidated. The aim of this multicentric study was to define the clinical phenotype and neurobehavioral features of a large cohort of subjects with a neuroradiologically confirmed diagnosis of JS.

Cognitive training modifies frequency EEG bands and neuropsychological measures in Rett syndrome.

Rett syndrome (RS) is a childhood neurodevelopmental disorder characterized by a primary disturbance in neuronal development. Neurological abnormalities in RS are reflected in several behavioral and cognitive impairments such as stereotypies, loss of speech and hand skills, gait apraxia, irregular breathing with hyperventilation while awake, and frequent seizures. Cognitive training can enhance both neuropsychological and neurophysiological parameters.

Effects of Maternal Iodine Nutrition and Thyroid Status on Cognitive Development in Offspring: A Pilot Study.

Background And Objective: Maternal iodine nutrition and thyroid status may influence neurocognitive development in offspring. This study investigated the effects on the intelligence quotient (IQ) of children born to mothers with different levels of iodine supplementation, with or without the administration of levothyroxine (LT4), prior to and during pregnancy.

Patients And Methods: This pilot, prospective, observational study included four study groups, each comprising 15 mother-child pairs, identified on the basis of maternal histories of iodized salt consumption and LT4 treatment prior to and during pregnancy.

Pediatric Hashimoto's encephalopathy with peripheral nervous system involvement.

Hashimoto encephalopathy is a syndrome of encephalopathy associated with elevated concentration of circulating serum anti-thyroid antibodies usually responsive to steroid therapy. We report a 13-year-old girl with Hashimoto encephalopathy and peripheral nervous system involvement. The child had experienced high-grade pyrexia, global headache and sleeplessness.

Long-term neuropsychiatric follow-up in hyperprolinemia type I.

The neuropsychiatric phenotype associated with hyperprolinemia type I (HPI) is still under debate. To our knowledge, no long-term follow-up on patients with HPI has been reported so far. We have previously described the clinical, biochemical, and molecular features of four patients with HPI.

Role of plasma homocysteine levels and MTHFR polymorphisms on IQ scores in children and young adults with epilepsy treated with antiepileptic drugs.

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. High plasma total Hcy (tHcy) has been quite frequently reported in patients with epilepsy treated with antiepileptic drugs (AEDs) mainly related to plasma folate reduction induced by AEDs themselves. The role of C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene (MTHFR) on the increase of plasma tHcy in patients with epilepsy taking AEDs is still controversial.

Pediatric idiopathic intracranial hypertension and the underlying endocrine-metabolic dysfunction: a pilot study.

Aim: To unravel the potential idiopathic intracranial hypertension (IIH) endocrine-metabolic comorbidities by studying the natural (and targeted drug-modified) history of disease in children. IIH is a disorder of unclear pathophysiology, characterized by raised intracranial pressure without hydrocephalus or space-occupying lesion coupled with normal cerebrospinal fluid (CSF) composition.

Methods: Retrospective study (years 2001-2010) of clinical records and images and prospective follow-up (years 2010-2013) in 15 children (11 girls, 4 boys; aged 5-16 years) diagnosed previously as "IIH", according to the criteria for pediatric IIH proposed by Rangwala, at four university pediatric centers in northern, central, and southern Italy.

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

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.

Acute cerebellar ataxia following meningococcal group C conjugate vaccination.

Acute cerebellar ataxia is the most common cause of childhood ataxia, usually resulting from infections or vaccinations. Cases of acute cerebellar ataxia have been reported as a consequence of several viral and bacterial infections as well as immunizing agents, such as varicella, influenza, hepatitis B, and diphtheria-pertussis-tetanus vaccines. Although immunization with meningococcal group C conjugate vaccines has been associated with several neurological side effects, acute cerebellar ataxia has not been previously reported.

PRRT2 mutations in familial infantile seizures, paroxysmal dyskinesia, and hemiplegic migraine.

Objective: To perform a clinical and genetic study of a family with benign familial infantile seizures (BFIS) and, upon finding a PRRT2 gene mutation, to study a cohort of probands with a similar phenotype. We extended the study to all available family members to find out whether PRRT2 mutations cosegregated with additional symptoms.

Methods: We carried out a clinical and genealogic study of a 3-generation family and of 32 additional probands with BFIS (11 families), infantile convulsions and paroxysmal choreoathetosis (ICCA) (9 families), BFIS/generalized epilepsy with febrile seizures plus (5 families), and sporadic benign neonatal or infantile seizures (7 probands/families).

Peritrigonal and temporo-occipital heterotopia with corpus callosum and cerebellar dysgenesis.

Objective: To describe a homogeneous subtype of periventricular nodular heterotopia (PNH) as part of a newly defined malformation complex.

Methods: Observational study including review of brain MRI and clinical findings of a cohort of 50 patients with PNH in the temporo-occipital horns and trigones, mutation analysis of the FLNA gene, and anatomopathologic study of a fetal brain.

Results: There were 28 females and 22 males.

A new form of alpha-dystroglycanopathy associated with severe drug-resistant epilepsy and unusual EEG features.

We describe two unrelated girls with congenital muscular dystrophy associated with alpha-dystroglycan deficit with no identified genetic defect, both presenting severe drug-resistant epilepsy with predominant myoclonic seizures and an unusual similar EEG pattern. Severe epilepsy has been unusually described in patients with congenital muscular dystrophies, mainly associated with Walker-Warburg, Fukuyama and muscle-eye-brain diseases. [Published with video sequences].

Pontine Tegmental Cap Dysplasia: developmental and cognitive outcome in three adolescent patients.

Pontine Tegmental Cap Dysplasia (PTCD) is a recently described, rare disorder characterized by a peculiar cerebellar and brainstem malformation. Nineteen patients have been reported to date, of which only one in the adolescent age, and data on the clinical, cognitive and behavioural outcome of this syndrome are scarce. Here we describe three adolescent patients with PTCD.

A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome.

Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein.

Type I hyperprolinemia and proline dehydrogenase (PRODH) mutations in four Italian children with epilepsy and mental retardation.

Type I hyperprolinemia (HPI) is an autosomal recessive disorder caused by proline oxidase deficiency. This enzyme is encoded by the proline dehydrogenase (PRODH) gene on 22q11. The functional consequences of different PRODH mutations on proline oxidase activity have been characterized in vitro.

Efficacy of folic acid in children with migraine, hyperhomocysteinemia and MTHFR polymorphisms.

MTHFR gene variants C677T and A1298C seem to be related to an increased risk of migraine. Folates' metabolism could play a role in the pathophysiology of migraine. We supplemented 16 children with migraine, hyperhomocysteinemia, and MTHFR polymorphisms with folic acid and obtained a resolution/reduction of migraine attacks.

Mutational analysis of EFHC1 gene in Italian families with juvenile myoclonic epilepsy.

Objectives: Mutations in the EFHC1 gene have been reported in six juvenile myoclonic epilepsy (JME) families from Mexico and Belize. In this study, we screened 27 unrelated JME Italian families for mutations in the EFHC1 gene.

Materials And Methods: Twenty-seven families (86 affected individuals, 52 women) with at least two affected members with JME were selected.

Ictal and interictal EEG abnormalities in ADHD children recorded over night by video-polysomnography.

In this paper we explore the prevalence of ictal and interictal epileptiform discharges (IEDs) and sleep disorders in ADHD children referred to a sleep clinic for all night video-PSG. Forty-two ADHD outpatients (35 males and 7 females) underwent video-PSG and a behavioural/neuropsychological assessment. Spearman correlation coefficients (p<0.

Neuropsychological deficits in monozygotic twins with childhood epilepsy with occipital paroxysms.

We report a unique pair of monozygotic twins with childhood epilepsy with occipital paroxysms who showed subtle cognitive deficits. The twin with a more severe epileptic disorder showed a more severe impairment of cognitive functioning. We suggest that epileptic focus may act as an element of disturbance in the development of primary functions and may give rise to a neuropsychological impairment proportionate to the severity of the epileptic activity.

Status gelasticus associated with levetiracetam as add-on treatment.

We report the case of a five-year-old girl, presenting with difficult-to-treat, symptomatic focal epilepsy, who developed status gelasticus following the introduction of levetiracetam as add-on treatment to oxcarbazepine and diazepam. Gelastic seizures were documented by video-EEG and were responsive to i.v.

Early impairment of synaptic plasticity in patients with Down's syndrome.

We investigated synaptic plasticity in persons with Down' syndrome (DS) and control subjects used paired associative stimulation (PAS) protocol, a paradigm capable of producing long-term potentiation (LTP)-like changes in the sensorimotor system. After PAS, patients showed less LTP-like plasticity compared to control subjects. Abnormal motor cortex synaptic plasticity may play a role in the development of motor signs in DS.

Novel CLN1 mutation in two Italian sibs with late infantile neuronal ceroid lipofuscinosis.

We detected a novel CLN1 mutation (c.125-15t>g) in two Italian siblings. The clinical phenotype is that of a variant late-infantile neuronal ceroid lipofuscinosis and consisted of early-onset visual loss, psychomotor deterioration, and seizures.

antiphospholipid antibodies syndrome associated with hyperhomocysteinemia related to MTHFR Gene C677T and A1298C heterozygous mutations in a young man with idiopathic hypoparathyroidism (DiGeorge syndrome).

Context: Antiphospholipid syndrome (APS, or Hughes' syndrome) is a systemic autoimmune disorder characterized by antiphospholipid antibody positivity, which may lead to arterial and/or venous thrombosis. Hyperhomocysteinemia (HHcy), variously associated with 5,10-methylene tetrahydrofolate reductase (MTHFR) gene point mutations, is also implicated in thromboembolic events. The association of APS and HHcy has already been described but has never been reported in patients with DiGeorge syndrome (DGS), the most common contiguous-gene deletion syndrome (22q11.