Clinical, developmental and serotonemia phenotyping of a sample of 70 Italian patients with Phelan-McDermid Syndrome.

Background: Phelan-McDermid syndrome (PMS) is caused by monoallelic loss or inactivation at the SHANK3 gene, located in human chr 22q13.33, and is often associated with Autism Spectrum Disorder (ASD).

Objectives: To assess the clinical and developmental phenotype in a novel sample of PMS patients, including for the first time auxometric trajectories and serotonin blood levels.

Cognitive, behavioral and socio-communication skills as predictors of response to Early Start Denver Model: a prospective study in 32 young children with Autism Spectrum Disorder.

Introduction: The effectiveness of early interventions in young autistic children is well established, but there is great interindividual variability in treatment response. Predictors of response to naturalistic developmental behavioral interventions (NDBI), like the Early Start Denver Model (ESDM), are needed.

Methods: We conducted an exploratory study to prospectively seek predictors of response in 32 young children treated with ESDM after receiving an ASD diagnosis.

Diagnostic yield and clinical impact of chromosomal microarray analysis in autism spectrum disorder.

Background: Autism spectrum disorder (ASD) is characterized by high heritability estimates and recurrence rates; its genetic underpinnings are very heterogeneous and include variable combinations of common and rare variants. Array-comparative genomic hybridization (aCGH) offers significant sensitivity for the identification of copy number variants (CNVs), which can act as susceptibility or causal factors for ASD.

Methods: The aim of this study was to evaluate both diagnostic yield and clinical impact of aCGH in 329 ASD patients of Italian descent.

Urinary Untargeted Metabolic Profile Differentiates Children with Autism from Their Unaffected Siblings.

Autism Spectrum Disorder (ASD) encompasses a clinical spectrum of neurodevelopmental conditions that display significant heterogeneity in etiology, symptomatology, and severity. We previously compared 30 young children with idiopathic ASD and 30 unrelated typically-developing controls, detecting an imbalance in several compounds belonging mainly to the metabolism of purines, tryptophan and other amino acids, as well as compounds derived from the intestinal flora, and reduced levels of vitamins B6, B12 and folic acid. The present study describes significant urinary metabolomic differences within 14 pairs, including one child with idiopathic ASD and his/her typically-developing sibling, tightly matched by sex and age to minimize confounding factors, allowing a more reliable identification of the metabolic fingerprint related to ASD.

Efficacy and Safety of Q10 Ubiquinol With Vitamins B and E in Neurodevelopmental Disorders: A Retrospective Chart Review.

Increased oxidative stress and defective mitochondrial functioning are shared features among many brain disorders. The aim of this study was to verify retrospectively the clinical efficacy and safety of a metabolic support therapy with Q10 ubiquinol, vitamin E and complex-B vitamins in various neurodevelopmental disorders. This retrospective chart review study included 59 patients (mean age 10.

Gut mobilization improves behavioral symptoms and modulates urinary p-cresol in chronically constipated autistic children: A prospective study.

Chronic constipation is common among children with ASD and is associated with more severe hyperactivity, anxiety, irritability, and repetitive behaviors. Young autistic children with chronic constipation display higher urinary, and foecal concentrations of p-cresol, an aromatic compound produced by gut bacteria, known to negatively affect brain function. Acute p-cresol administration to BTBR mice enhances anxiety, hyperactivity and stereotypic behaviors, while blunting social interaction.

Genotype-phenotype correlation in Phelan-McDermid syndrome: A comprehensive review of chromosome 22q13 deleted genes.

Phelan-McDermid syndrome (PMS, OMIM #606232), also known as chromosome 22q13 deletion syndrome, is a rare genetic disorder characterized by intellectual disability, hypotonia, delayed or absent speech, motor impairment, autism spectrum disorder, behavioral anomalies, and minor aspecific dysmorphic features. Haploinsufficiency of SHANK3, due to intragenic deletions or point mutations, is sufficient to cause many neurobehavioral features of PMS. However, several additional genes located within larger 22q13 deletions can contribute to the great interindividual variability observed in the PMS phenotype.

The pediatric psychopharmacology of autism spectrum disorder: A systematic review - Part I: The past and the present.

Autism Spectrum Disorder (ASD) is a severe and lifelong neurodevelopmental disorder, with high social costs and a dramatic burden on the quality of life of patients and family members. Despite its high prevalence, reaching 1/54 children and 1/45 adults in the United States, no pharmacological treatment is still directed to core symptoms of ASD, encompassing social and communication deficits, repetitive behaviors, restricted interests, and abnormal sensory processing. The purpose of this review is to provide an overview of the state-of-the-art of psychopharmacological therapy available today for ASD in children and adolescents, in order to foster best practices and to organize new strategies for future research.

Huntingtin gene CAG repeat size affects autism risk: Family-based and case-control association study.

The Huntingtin (HTT) gene contains a CAG repeat in exon 1, whose expansion beyond 39 repeats consistently leads to Huntington's disease (HD), whereas normal-to-intermediate alleles seemingly modulate brain structure, function and behavior. The role of the CAG repeat in Autism Spectrum Disorder (ASD) was investigated applying both family-based and case-control association designs, with the SCA3 repeat as a negative control. Significant overtransmission of "long" CAG alleles (≥17 repeats) to autistic children and of "short" alleles (≤16 repeats) to their unaffected siblings (all p < 10 ) was observed in 612 ASD families (548 simplex and 64 multiplex).

FARP-1 deletion is associated with lack of response to autism treatment by early start denver model in a multiplex family.

Background: Children with autism spectrum disorder (ASD) display impressive clinical heterogeneity, also involving treatment response. Genetic variants can contribute to explain this large interindividual phenotypic variability.

Methods: Array-CGH (a-CGH) and whole genome sequencing (WGS) were performed on a multiplex family with two small children diagnosed with ASD at 17 and 18 months of age.

The psychopharmacology of autism spectrum disorder and Rett syndrome.

Autism spectrum disorder (ASD) appears in early childhood and is characterized by persistent deficits in communication and social interaction, as well as restricted interests, repetitive behaviors, and unusual sensory issues. ASD can be idiopathic or syndromic, in the latter case representing one of the many manifestations of a genetic disorder, such as Rett syndrome. Psychopharmacology cannot directly ameliorate core autistic symptoms, but rather aims at treating comorbid disorders, such as ADHD, sleep disturbances, psychomotor agitation and aggressiveness, seizures, and anxiety.

Phenotypic spectrum of NRXN1 mono- and bi-allelic deficiency: A systematic review.

Neurexins are presynaptic cell adhesion molecules critically involved in synaptogenesis and vesicular neurotransmitter release. They are encoded by three genes (NRXN1-3), each yielding a longer alpha (α) and a shorter beta (β) transcript. Deletions spanning the promoter and the initial exons of the NRXN1 gene, located in chromosome 2p16.

Evidence that ITGB3 promoter variants increase serotonin blood levels by regulating platelet serotonin transporter trafficking.

Elevated serotonin (5-HT) blood levels, the first biomarker identified in autism research, has been consistently found in 20-30% of patients with Autism Spectrum Disorder (ASD). Hyperserotonemia is mainly due to greater 5-HT uptake into platelets, mediated by the 5-HT transporter (SERT) located at the platelet plasma membrane. The protein complex involved in platelet SERT trafficking and externalization includes integrin β3, the beta subunit of the platelet membrane adhesive GP IIb/IIIa.