Heterozygosity for loss-of-function variants in LZTR1 is associated with isolated multiple café-au-lait macules.

Purpose: Pathogenic LZTR1 variants cause schwannomatosis and dominant/recessive Noonan syndrome (NS). We aim to establish an association between heterozygous loss-of-function LZTR1 alleles and isolated multiple café-au-lait macules (CaLMs).

Methods: A total of 849 unrelated participants with multiple CaLMs, lacking pathogenic/likely pathogenic NF1 and SPRED1 variants, underwent RASopathy gene panel sequencing.

The detection of a strong episignature for Chung-Jansen syndrome, partially overlapping with Börjeson-Forssman-Lehmann and White-Kernohan syndromes.

Chung-Jansen syndrome is a neurodevelopmental disorder characterized by intellectual disability, behavioral problems, obesity and dysmorphic features. It is caused by pathogenic variants in the PHIP gene that encodes for the Pleckstrin homology domain-interacting protein, which is part of an epigenetic modifier protein complex. Therefore, we hypothesized that PHIP haploinsufficiency may impact genome-wide DNA methylation (DNAm).

Narcissistic Personality Disorder as Prodromal Feature of Early-Onset, GRN-Positive bvFTD: A Case Report.

Background: Behavioral variant frontotemporal dementia (bvFTD) typically involves subtle changes in personality that can delay a timely diagnosis.

Objective: Here, we report the case of a patient diagnosed of GRN-positive bvFTD at the age of 52 presenting with a 7-year history of narcissistic personality disorder, accordingly to DSM-5 criteria.

Methods: The patient was referred to neurological and neuropsychological examination.

Organization and Activity of Italian Echocardiographic Laboratories: A Survey of the Italian Society of Echocardiography and Cardiovascular Imaging.

Background: The Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand better how different echocardiographic modalities are used and accessed in Italy.

Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved via an electronic survey based on a structured questionnaire, uploaded on the SIECVI website.

Case report: Functional characterization of a novel intronic variant in patients with CHARGE syndrome.

Because CHARGE syndrome is characterized by high clinical variability, molecular confirmation of the clinical diagnosis is of pivotal importance. Most patients have a pathogenic variant in the gene; however, variants are distributed throughout the gene and most cases are due to mutations. Often, assessing the pathogenetic effect of a variant can be challenging, requiring the design of a unique assay for each specific case.

Behavioral profiling in children and adolescents with Malan syndrome.

Malan syndrome (MALNS) is an ultra-rare genetic disorder caused by heterozygous chromosomal microdeletions involving the 19p13.2 region or loss-of-function variants in the gene. It is characterized by specific phenotypical features, intellectual disability (ID), and limitations in adaptive functioning and behavioral problems.

A deep phenotyping experience: up to date in management and diagnosis of Malan syndrome in a single center surveillance report.

Background: Malan syndrome (MALNS) is a recently described ultrarare syndrome lacking guidelines for diagnosis, management and monitoring of evolutive complications. Less than 90 patients are reported in the literature and limited clinical information are available to assure a proper health surveillance.

Results: A multidisciplinary team with high expertise in MALNS has been launched at the "Ospedale Pediatrico Bambino Gesù", Rome, Italy.

Novel genetic variants of KHDC3L and other members of the subcortical maternal complex associated with Beckwith-Wiedemann syndrome or Pseudohypoparathyroidism 1B and multi-locus imprinting disturbances.

Background: Beckwith-Wiedemann syndrome (BWS) and Pseudohypoparathyroidism type 1B (PHP1B) are imprinting disorders (ID) caused by deregulation of the imprinted gene clusters located at 11p15.5 and 20q13.32, respectively.

Genotypes and phenotypes heterogeneity in PIK3CA-related overgrowth spectrum and overlapping conditions: 150 novel patients and systematic review of 1007 patients with PIK3CA pathogenetic variants.

Background: Postzygotic activating variants cause several phenotypes within the -related overgrowth spectrum (PROS). Variant strength, mosaicism level, specific tissue involvement and overlapping disorders are responsible for disease heterogeneity. We explored these factors in 150 novel patients and in an expanded cohort of 1007 mutated patients, analysing our new data with previous literature to give a comprehensive picture.

DNA methylation episignature testing improves molecular diagnosis of Mendelian chromatinopathies.

Purpose: Chromatinopathies include more than 50 disorders caused by disease-causing variants of various components of chromatin structure and function. Many of these disorders exhibit unique genome-wide DNA methylation profiles, known as episignatures. In this study, the methylation profile of a large cohort of individuals with chromatinopathies was analyzed for episignature detection.

Novel Frameshift Mutation in a Patient Affected by a Syndromic Form of Neurodevelopmental Disorder.

The cohesin complex is a large evolutionary conserved functional unit which plays an essential role in DNA repair and replication, chromosome segregation and gene expression. It consists of four core proteins, SMC1A, SMC3, RAD21, and STAG1/2, and by proteins regulating the interaction between the complex and the chromosomes. Mutations in the genes coding for these proteins have been demonstrated to cause multisystem developmental disorders known as "cohesinopathies".

Protein instability associated with AARS1 and MARS1 mutations causes trichothiodystrophy.

Trichothiodystrophy (TTD) is a rare hereditary neurodevelopmental disorder defined by sulfur-deficient brittle hair and nails and scaly skin, but with otherwise remarkably variable clinical features. The photosensitive TTD (PS-TTD) forms exhibits in addition to progressive neuropathy and other features of segmental accelerated aging and is associated with impaired genome maintenance and transcription. New factors involved in various steps of gene expression have been identified for the different non-photosensitive forms of TTD (NPS-TTD), which do not appear to show features of premature aging.

Whole Exome Sequencing Reveals a Novel In-Frame Deletion in a Boy with Global Developmental Delay, Absent Speech, Dysmorphic Features, and Cerebral Anomalies.

Neurodevelopmental disorders (NDDs) are a group of highly prevalent, clinically and genetically heterogeneous pediatric disorders comprising, according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-V), intellectual disability, developmental delay, autism spectrum disorders, and other neurological and cognitive disorders manifesting in the developmental age. To date, more than 1000 genes have been implicated in the etiopathogenesis of NNDs. Among them, (OMIM # 607270) encodes a protein involved in neural migration and neuritogenesis, and causes NNDs with different molecular mechanisms including copy number variations, single or multiple exonic deletion and single nucleotide variants.

Epicardial Adipose Tissue and IL-13 Response to Myocardial Injury Drives Left Ventricular Remodeling After ST Elevation Myocardial Infarction.

Introduction: Left ventricular (LV) remodeling after ST-segment elevation myocardial infarction (STEMI) is explained only in part by the infarct size, and the inter-patient variability may be ascribed to different inflammatory response to myocardial injury. Epicardial adipose tissue (EAT) is a source of inflammatory mediators which directly modulates the myocardium. EAT increase is associated to several cardiovascular diseases; however, its response to myocardial injury is currently unknown.

Customised next-generation sequencing multigene panel to screen a large cohort of individuals with chromatin-related disorder.

Background: The regulation of the chromatin state by epigenetic mechanisms plays a central role in gene expression, cell function, and maintenance of cell identity. Hereditary disorders of chromatin regulation are a group of conditions caused by abnormalities of the various components of the epigenetic machinery, namely writers, erasers, readers, and chromatin remodelers. Although neurological dysfunction is almost ubiquitous in these disorders, the constellation of additional features characterizing many of these genes and the emerging clinical overlap among them indicate the existence of a community of syndromes.

Correction to: Case report: acute clinical presentation and neonatal management of primary hyperparathyroidism due to a novel CaSR mutation.

In the published article [1], an error has been noticed in the author group section.

Long QT syndrome in chromosome 7q35q36.3 deletion involving KCNH2 gene: Warning for chlorpheniramine prescription.

Background: The deletion of the distal 7q region is a rare chromosomal syndrome characterized by wide phenotypic manifestations including growth and psychomotor delay, facial dysmorphisms, and genitourinary malformations.

Methods: We describe a 6-year-old child with a 12-Mb deletion of the region 7q35q36.3.

Pericardial thrombus and cardiac tamponade after pericardiocentesis with intact heart walls.

A young patient affected by a lung neoplasm, presented at emergency department with cardiac tamponade, underwent pericardiocentesis with a prompt restoration of hemodynamic stability. An hour later, the patient presented again signs of tamponade, without evidence of fluids in the drainage that was left in pericardial space. The echocardiography revealed an intrapericardial thrombus compressing the right chambers.

Case report: acute clinical presentation and neonatal management of primary hyperparathyroidism due to a novel CaSR mutation.

Background: Neonatal severe primary hyperparathyroidism (NSHPT) is a rare autosomal recessive disorder of calcium homeostasis, characterized by striking hyperparathyroidism, marked hypercalcemia and hyperparathyroid bone disease. We report the case of a newborn with a novel homozygous mutation of the CaSR, treated by successful subtotal parathyroidectomy, who had an acute presentation of the disease, i.e.

Refinement of the critical 7p22.1 deletion region: Haploinsufficiency of ACTB is the cause of the 7p22.1 microdeletion-related developmental disorders.

Non-recurrent microdeletion (≤2 Mb in size) in 7p22.1 is a rarely described cytogenetic aberration, only recently reported in patients with developmental delay/intellectual disability, short stature and microcephaly. The size of the deletions ranged from 0.

Clinical and molecular characterization of an emerging chromosome 22q13.31 microdeletion syndrome.

Microdeletion of chromosome 22q13.31 is a very rare condition. Fourteen patients have been annotated in public databases but, to date, a clinical comparison has not been done and, consequently, a specific phenotype has not been delineated yet.