Management of respiratory issues in patients with Rett syndrome: Italian experts' consensus using a Delphi approach.

Background: Despite the publication of the 2020 guidelines on how to manage Rett Syndrome (RS), some fundamental topics are still open, in particular respiratory problems.

Objective: Identification and reinforcement of current recommendations concerning the management of respiratory issues in RS patients.

Materials And Methods: Using a Delphi approach, the leading group reviewed the literature and formulated 14 statements.

Care Issues in Patients with Rett Syndrome: A Parental Perspective.

Background: The purpose of this study is to better understand the way caregivers of patients with Rett syndrome perceive the quality of the health care services they receive and identify its main shortcomings.

Methods: A survey was distributed to all caregivers who are part of AIRETT (the Italian Association of Relatives of Patients with RS). The survey gathered information on the management of relatives of patients with Rett syndrome.

Cardiac phenotype in -related syndromes: A multicenter cohort study.

Objective: To define the risks and consequences of cardiac abnormalities in -related syndromes.

Methods: Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an knock-in mouse (Mashl) to determine the sequence of events in seizure-related cardiac death.

Pathogenic Variants in and in Genes for GABAa Receptor Subunities Cause Atypical Rett/Rett-like Phenotypes.

Rett syndrome (RTT) is a neurodevelopmental disorder, affecting 1 in 10,000 girls. Intellectual disability, loss of speech and hand skills with stereotypies, seizures and ataxia are recurrent features. Stringent diagnostic criteria distinguish classical Rett, caused by a pathogenic variant in 95% of cases, from atypical girls, 40-73% carrying variants, and rarely and alterations.

Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review.

Aicardi-Goutières syndrome (AGS) is a genetically determined early onset encephalopathy characterized by cerebral calcification, leukodystrophy, and increased expression of interferon-stimulated genes (ISGs). Up to now, seven genes () have been associated with an AGS phenotype. Next Generation Sequencing (NGS) analysis was performed on 51 AGS patients and interferon signature (IS) was investigated in 18 AGS patients and 31 healthy controls.

Analysis of the Phenotypes in the Rett Networked Database.

Rett spectrum disorder is a progressive neurological disease and the most common genetic cause of intellectual disability in females. is the major causative gene. In addition, and mutations have been reported in Rett patients, especially with the atypical presentation.

Personality profile and health-related quality of life in adults with previous continuous spike-waves during slow sleep syndrome.

Introduction: Epilepsy with continuous spike-waves during slow sleep syndrome (CSWSS) is characterized by various seizure types, a characteristic EEG pattern and neuropsychological disorders. The main purpose of this study was to evaluate the long-term outcome of CSWSS occurred in childhood and to evaluate the variables that could influence the quality of social adaptation and the personality profile.

Material And Methods: This is a prospective study on 24 young adults with previous CSWSS (median age 24.

PANDAS and PANS: Clinical, Neuropsychological, and Biological Characterization of a Monocentric Series of Patients and Proposal for a Diagnostic Protocol.

Whether PANS (pediatric acute-onset neuropsychiatric syndrome) and PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) represent true clinical entities is debated and data for a characteristic phenotype are still controversial. In this study, we aim to characterize clinical, neuropsychological, and biochemical aspects in a sample of PANS and PANDAS patients. Patients fulfilling a clinical diagnosis of PANS or PANDAS from 2014 to 2017 were enrolled.

Intragenic duplication of KCNQ5 gene results in aberrant splicing leading to a premature termination codon in a patient with intellectual disability.

The KCNQ5 gene, widely expressed in the brain, encodes a voltage-gated potassium channel (Kv7.5) important for neuronal function. Here, we report a novel KCNQ5 intragenic duplication at 6q13 spanning about 239 Kb of genomic DNA, identified by array comparative genomic hybridization (array-CGH).

Prospective motor control obeys to idiosyncratic strategies in autism.

Disturbance of primary prospective motor control has been proposed to contribute to faults in higher mind functions of individuals with autism spectrum disorder, but little research has been conducted to characterize prospective control strategies in autism. In the current study, we applied pattern-classification analyses to kinematic features to verify whether children with autism spectrum disorder (ASD) and typically developing (TD) children altered their initial grasp in anticipation of self- and other-actions. Results indicate that children with autism adjusted their behavior to accommodate onward actions.

Intellectual efficiency in children and adolescents with spina bifida myelomeningocele and shunted hydrocephalus.

We studied the intellectual profiles of 13 Italian children diagnosed with spina bifida myelomeningocele and shunted hydrocephalus (MMC HC) against a control group of children. The results showed that MMC HC group had lower performance in all subtests, four indices, and the FSIQ of the Wechsler Intelligence Scale for Children, forth-edition. The MMC HC group showed flat cognitive profiles between subtests within each index and between four core indices.

ATP1A3 spectrum disorders: A video-documented history of 7 genetically confirmed early onset cases.

Mutations in the ATP1A3 gene, which encodes the alpha-subunit of sodium-potassium ATPase, are related to a spectrum of neurological diseases including Rapid onset Dystonia-Parkinsonism (RDP), Alternating Hemiplegia of Childhood (AHC) and Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss (CAPOS) syndrome. Moreover, an increasing number of patients with intermediate and non classical phenotypes have been reported. Herein we describe 7 patients with 6 different de novo ATP1A3 mutations, and we focus on paroxysmal and chronic movement disorders with the help of video documentation.

One hand, two hands, two people: Prospective sensorimotor control in children with autism.

Where grasps are made reveals how grasps are planned. The grasp height effect predicts that, when people take hold of an object to move it to a new position, the grasp height on the object is inversely related to the height of the target position. In the present study, we used this effect as a window into the prospective sensorimotor control of children with autism spectrum disorders without accompanying intellectual impairment.

Combined early treatment in hemiplegic attacks related to CACNA1A encephalopathy with brain oedema: Blocking the cascade?

Introduction Variants in the CACNA1A gene on chromosome 19p13 result in a spectrum of neurological phenotypes ranging from familial or sporadic hemiplegic migraine to congenital or progressive encephalopathies. Patients with CACNA1A variants often show acute attacks with ataxia or hemiplegia till coma, sometimes related to unilateral brain oedema. No guidelines for the medical management of these attacks are available since treatment is empiric, and many cases do not respond to common antimigraine drugs.

Blood oxidative stress and metallothionein expression in Rett syndrome: Probing for markers.

Objectives: Oxidative stress seems to be involved in Rett syndrome (RTT). The aim of this study was to assess the antioxidant status in RTT children with MECP2 gene mutations with respect to healthy controls, and to explore novel blood antioxidant markers for RTT severity.

Methods: In erythrocytes from RTT females aged 2-14 years (n = 27) and age-matched controls (n = 27), we measured the levels of malonaldehyde and the activity of two antioxidant enzymes, Cu/Zn-superoxide dismutase and catalase, by spectrophotometric assays.

Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype.

Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur.

Clinical and molecular characterization of a patient with interstitial 6q21q22.1 deletion.

Background: Interstitial 6q deletions, involving the 6q15q25 chromosomal region, are rare events characterized by variable phenotypes and no clear karyotype/phenotype correlation has been determined yet.

Results: We present a child with a 6q21q22.1 deletion, characterized by array-CGH, associated with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, skeletal, muscle, and brain anomalies.

Antiepileptic drugs in Rett Syndrome.

Purpose: We investigated drugs most often used to treat epilepsy in Rett Syndrome and their efficacy in a large cohort of Italian patients.

Methods: This is a multi-centre retrospective study. Data of 165 Rett subjects were collected from the patients' files, and hospital charts.

Epilepsy in Rett syndrome--lessons from the Rett networked database.

Objective: Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by mutations in the MECP2 gene, and characterized by cognitive and communicative regression, loss of hand use, and midline hand stereotypies. Epilepsy is a core symptom, but literature is controversial regarding genotype-phenotype correlation. Analysis of data from a large cohort should overcome this shortcoming.

Inferior olivary nucleus involvement in pediatric neurodegenerative disorders: does it play a role in neuroimaging pattern-recognition approach?

The diagnostic work up of neurometabolic/degenerative disorders is complex. In such context, identification of neuroradiological features suggestive of specific diagnoses is useful to prompt further diagnostic tests. Involvement of the inferior olivary nucleus (ION) has been reported in several pathologic conditions, either as a primary manifestation of disease or secondary to hypertrophic olivary degeneration (HOD).

Epileptic encephalopathy with continuous spike and wave during sleep associated to periventricular leukomalacia.

Periventricular leukomalacia is the most common type of brain injury in premature infants. Our aim is to describe the frequency and the features of epilepsy in a single-center population of 137 children with periventricular leukomalacia. Forty-two of the 137 (31%) patients presented epilepsy.

Lack of SLC2A1 (glucose transporter 1) mutations in 30 Italian patients with alternating hemiplegia of childhood.

Alternating hemiplegia of childhood is a rare, predominantly sporadic disorder. Diagnosis is clinical, and little is known about genetics. Glucose transporter 1 deficiency syndrome shares with alternating hemiplegia of childhood paroxysmal and nonparoxysmal symptoms.