Clinical genetic services in the Emilia-Romagna region, Italy: current activity and open issues: a mixed-method study.

In 2002, in the Emilia-Romagna region of Italy, a comprehensive strategic plan was developed with the aim of improving the integration and efficiency of the genetic services. Two decades later, this report aims to explore the current functioning of the regional network, with special focus on clinical genetics in the evolving scenarios. To this aim, we analyzed the activity data of the medical genetics services in the region, to identify and possibly improve currently open issues.

De novo variants in LRRC8C resulting in constitutive channel activation cause a human multisystem disorder.

Volume-regulated anion channels (VRACs) are multimeric proteins composed of different paralogs of the LRRC8 family. They are activated in response to hypotonic swelling, but little is known about their specific functions. We studied two human individuals with the same congenital syndrome affecting blood vessels, brain, eyes, and bones.

Sensory-Motor Polyneuropathy in an 11-year- old Girl with a Pathogenic Variant in SMC1A: A Case Report.

Pathogenic variants in the gene are often dominant-negative and cause an X-linked form of Cornelia de Lange syndrome (CdLS) with growth retardation and typical facial features. However, rare variants cause a developmental and epileptic encephalopathy (DEE) with intractable early-onset epilepsy that is absent in CdLS. Here we describe an 11-year-old girl with epilepsy, walking disorder, and neurodevelopmental disorder.

Two novel compound heterozygous HOXB1 variants in congenital facial palsy: A case report and a brief review of the literature.

Hereditary congenital facial palsy (HCFP) is a medical condition caused by dysfunction of the seventh cranial nerve. HCFP is characterized by feeding difficulties and dysmorphic features in the orofacial region. In some cases hearing loss, strabismus, limb malformations, and musculoskeletal defects may be associated.

Myhre syndrome in adulthood: clinical variability and emerging genotype-phenotype correlations.

Myhre syndrome (MS, MIM 139210) is a rare multisystemic disorder caused by recurrent pathogenic missense variants in SMAD4. The clinical features have been mainly documented in childhood and comprise variable neurocognitive development, recognizable craniofacial features, a short stature with a pseudo-muscular build, hearing loss, thickened skin, joint limitations, diverse cardiovascular and airway manifestations, and increased fibrosis often following trauma or surgery. In contrast, adults with MS are underreported obscuring potential clinical variability.

Early-onset dysphagia and severe neurodevelopmental disorder as early signs in a patient with two novel variants in NARS1: a case report and brief review of the literature.

Aminoacyl-tRNA synthetases (ARSs) aminoacylate tRNA molecules with their cognate amino acid, enabling information transmission and providing substrates for protein biosynthesis. They also take part in nontranslational functions, mediated by the presence of other proteins domains. Mutations in ARS genes have been described as responsive to numerous factors, including neurological, autoimmune, and oncological.

Heterozygous truncating variant of TAOK1 in a boy with periventricular nodular heterotopia: a case report and literature review of TAOK1-related neurodevelopmental disorders.

Background: Thousand and one amino-acid kinase 1 (TAOK1) encodes the MAP3K protein kinase TAO1, which has recently been displayed to be essential for neuronal maturation and cortical differentiation during early brain development. Heterozygous variants in TAOK1 have been reported in children with neurodevelopmental disorders, with or without macrocephaly, hypotonia and mild dysmorphic traits. Literature reports lack evidence of neuronal migration disorders in TAOK1 patients, although studies in animal models suggest this possibility.

Identification of the DNA methylation signature of Mowat-Wilson syndrome.

Mowat-Wilson syndrome (MOWS) is a rare congenital disease caused by haploinsufficiency of ZEB2, encoding a transcription factor required for neurodevelopment. MOWS is characterized by intellectual disability, epilepsy, typical facial phenotype and other anomalies, such as short stature, Hirschsprung disease, brain and heart defects. Despite some recognizable features, MOWS rarity and phenotypic variability may complicate its diagnosis, particularly in the neonatal period.

Animal displacement from marine energy development: Mechanisms and consequences.

For marine wave and tidal energy to successfully contribute to global renewable energy goals and climate change mitigation, marine energy projects need to expand beyond small deployments to large-scale arrays. However, with large-scale projects come potential environmental effects not observed at the scales of single devices and small arrays. One of these effects is the risk of displacing marine animals from their preferred habitats or their migration routes, which may increase with the size of arrays and location.

Genetic Epilepsies and Developmental Epileptic Encephalopathies with Early Onset: A Multicenter Study.

The genetic causes of epilepsies and developmental and epileptic encephalopathies (DEE) with onset in early childhood are increasingly recognized. Their outcomes vary from benign to severe disability. In this paper, we wished to retrospectively review the clinical, genetic, EEG, neuroimaging, and outcome data of patients experiencing the onset of epilepsy in the first three years of life, diagnosed and followed up in four Italian epilepsy centres (Epilepsy Centre of San Paolo University Hospital in Milan, Child Neurology and Psychiatry Unit of AUSL-IRCCS di Reggio Emilia, Pediatric Neurology Unit of Vittore Buzzi Children's Hospital, Milan, and Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia).

'A novel TRIP4 Variant Associated with Peripheral Neuropathy: Expanding the Clinical and Genetic Spectrum of ASC1-Related Myopathy'.

Activating Signal Cointegrator 1 complex (ASC-1 complex) is a ribonucleoprotein tetramer participating in transcriptional coactivation and RNA processing, consisting of four subunits: ASCC1-ASCC3 and ASC-1. Pathogenic variants in the TRIP4 and ASCC1 genes, encoding the ASC-1 and ASCC1 subunits, were recently described in congenital myopathic conditions without signs of motor neuron involvement, and Spinal Muscular Atrophy-like (SMA-like) phenotype with prenatal bone fractures. We present a novel pathogenic TRIP4 variant in two siblings with severe phenotype and mixed sensory-motor polyneuropathy.

Expanding Phenotype of -Related Neurodevelopmental Disorder: Case Report and Literature Review.

Introduction: Synaptotagmin 1 (SYT1), the predominant SYT isoform in the central nervous system, likely acts by promoting vesicle docking, deforming the plasma membrane via Ca-dependent membrane penetration.

Case Presentation: Here, we describe a 21-year-old woman harboring a novel variant in the gene, who presents with a complex phenotype, featuring severe intellectual disability, absent speech, behavioral abnormalities, motor stereotypies, dystonic posturing of her hands, a hyperkinetic movement disorder in her childhood, infantile hypotonia, sialorrhea, mild dysmorphic features, epilepsy, peculiar EEG findings, and severe scoliosis.

Discussion: Based on our case and literature review on the 22 previously described patients, we can confirm a complex neurodevelopmental disorder in which, unlike other synaptopathies, epilepsy is present in a subset of cases (including our patient: 5/23, 22%), although characteristic EEG changes are far more common (10/23, 43.

Severe Neurodevelopmental Disorder in Autosomal Recessive Spinocerebellar Ataxia 13 (SCAR13) Caused by Two Novel Frameshift Variants in GRM1.

Autosomal recessive spinocerebellar ataxia 13 (SCAR13) is a neurological disease characterized by psychomotor delay, mild to profound intellectual disability with poor or absent language, nystagmus, stance ataxia, and, if walking is acquired, gait ataxia. Epilepsy and polyneuropathy have also been documented in some patients. Cerebellar atrophy and/or ventriculomegaly may be present on brain MRI.

Diprosopus: A Rare Case of Craniofacial Duplication and a Systematic Review of the Literature.

In 1990, Gorlin et al. described four types of craniofacial duplications: (1) single mouth with duplication of the maxillary arch; (2) supernumerary mouth laterally placed with rudimentary segments; (3) single mouth with replication of the mandibular segments; and (4) true facial duplication, namely diprosopus. We describe a newborn born with wide-spaced eyes, a very broad nose, and two separate mouths.

Case Report: Sequential postzygotic mutation and gains of the paternal chromosome 11 carrying the mutated allele in a patient with epidermal nevus and rhabdomyosarcoma: evidence of a multiple-hit mechanism involving in oncogenic transformation.

We report a 7-year-old boy born with epidermal nevi (EN) arranged according to Blaschko's lines involving the face and head, right upper limb, chest, and left lower limb, who developed a left paratesticular embryonal rhabdomyosarcoma at 18 months of age. Parallel sequencing identified a gain-of-function variant (c.37G>C, p.

Split Hand-Foot and Deafness in a Patient with 7q21.13-q21.3 Deletion Not Including the Genes.

Split Hand-Foot Malformation (SHFM) is a congenital limb defect characterized by a median cleft of the hands and/or feet due to the absence/hypoplasia of the central rays. It may occur as part of a syndromic condition or as an isolated malformation. The most common of the six genetic loci identified for this condition is correlated to SHFM1 and maps in the 7q21q22 region.

Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature.

Background: KBG syndrome is caused by haploinsufficiency of and is characterised by macrodontia of upper central incisors, distinctive facial features, short stature, skeletal anomalies, developmental delay, brain malformations and seizures. The central nervous system (CNS) and skeletal features remain poorly defined.

Methods: CNS and/or skeletal imaging were collected from molecularly confirmed individuals with KBG syndrome through an international network.

Case report: Expanding the phenotype of -related intellectual disability syndrome and hyperkinetic movement disorder in differential diagnosis with epileptic seizures.

Objective: We aimed to report on previously unappreciated clinical features associated with -related intellectual disability (ID) syndrome, a rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, and language delay, with or without autistic features.

Methods: We performed whole-exome sequencing (WES) to molecularly characterize an individual presenting with ID, epilepsy, autism spectrum disorder, behavioral problems, and facial dysmorphisms as major features.

Results: WES allowed us to identify a previously unreported splice site variant, c.

Developmental and epileptic encephalopathy in a young Italian woman with a de novo missense variant in the CLCN4 gene: A case report.

Introduction: Raynaud-Claes syndrome is a very rare X-linked condition, characterized by intellectual disability, impaired language development, brain abnormalities, facial dysmorphisms and drug-resistant epilepsy. It is caused by loss-of-function variants in the CLCN4 gene, which encodes the 2Cl-/H + exchanger ClC-4, prominently expressed in the hippocampus and cerebellum. Different genotypic variants have been described, each exhibiting specific phenotypic characteristics.