Novel Genetic Variant in : Prenatal and Postnatal Neuroimaging Phenotype.

Objectives: To provide a comprehensive description of neuroradiologic findings in a patient with a probable pathogenic variant of , particularly in relation to pontine and cerebellar hypoplasia.

Methods: We first report prenatal and postnatal neuroradiologic phenotype of a female patient carrying a likely pathogenic variant and discuss its function.

Results: An ultrasound shows borderline ventriculomegaly, rotated cerebellar vermis, and dysgenetic corpus callosum.

Amnioreduction for Polyhydramnios in a Consecutive Series at a Single Center: Indications, Risks and Perinatal Outcomes.

Pregnancies complicated by severe polyhydramnios are associated with a high rate of underlying fetal anomaly. Amnioreduction may be offered to alleviate maternal symptoms. This is a retrospective study of amnioreductions performed on singleton and twin gestations complicated by symptomatic polyhydramnios between 2010 and 2023 at our tertiary referral center.

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).

Comparison of first-tier whole-exome sequencing with a multi-step traditional approach for diagnosing paediatric outpatients: An Italian prospective study.

Background: The recent guidelines suggest the use of genome-wide analyses, such as whole exome sequencing (WES), at the beginning of the diagnostic approach for cases with suspected genetic conditions. However, in many realities it still provides for the execution of a multi-step pathway, thus requiring several genetic tests to end the so-called 'diagnostic odyssey'.

Methods: We reported the results of GENE Project (Genomic analysis Evaluation NEtwork): a multicentre prospective cohort study on 125 paediatric outpatients with a suspected genetic disease in which we performed first-tier trio-WES, including exome-based copy number variation analysis, in parallel to a 'traditional approach' of two/three sequential genetic tests.

Case report: Early-onset parkinsonism among the neurological features in children with variants.

is expressed in cardiovascular and neurological tissues. In the brain, it has a role in pre- and post-natal maturation. Previously reported -mutated patients showed early-onset epilepsy and intellectual disability.

FDXR-associated disease: a challenging differential diagnosis with inflammatory peripheral neuropathy.

Background And Aims: Mutations in FDXR gene, involved in mitochondrial pathway, cause a rare recessive neurological disorder with variable severity of phenotypes. The most common presentation includes optic and/or auditory neuropathy, variably associated to developmental delay or regression, global hypotonia, pyramidal, cerebellar signs, and seizures. The review of clinical findings in previously described cases from literature reveals also a significant incidence of sensorimotor peripheral polyneuropathy (22.

The crucial role of titin in fetal development: recurrent miscarriages and bone, heart and muscle anomalies characterise the severe end of titinopathies spectrum.

Background: Titin truncating variants (TTNtvs) have been associated with several forms of myopathies and/or cardiomyopathies. In homozygosity or in compound heterozygosity, they cause a wide spectrum of recessive phenotypes with a congenital or childhood onset. Most recessive phenotypes showing a congenital or childhood onset have been described in subjects carrying biallelic TTNtv in specific exons.

Menkes disease complicated by concurrent ACY1 deficiency: A case report.

Menkes disease is an X-linked recessive condition caused by mutations in the gene, which leads to severe copper deficiency. Aminoacylase-1 deficiency is a rare inborn error of metabolism caused by homozygous or compound heterozygous variant in the gene, characterized by increased urinary excretion of specific N-acetyl amino acids. We report an infant with neurological findings such as seizures, neurodevelopmental delay and hypotonia.

Rock around DYRK1A: Ethnic diversity, clinical challenges.

DYRK1A-related intellectual disability is a recently described syndrome characterized by microcephaly, global developmental delay, impaired speech development, and distinctive facial features, which let to define it as a recognizable syndrome. Here we report four new patients of different ethnicity, broadening the clinical phenotype of the condition and highlighting how ethnic influences in the facial appearance could make it less recognizable.

Newborn screening for X-linked adrenoleukodystrophy in Italy: Diagnostic algorithm and disease monitoring.

Introduction: X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder caused by variants in the gene. The main phenotypes observed in men with X-ALD are primary adrenal insufficiency, adrenomyeloneuropathy, and cerebral ALD (cALD). Cerebral ALD consists of a demyelinating progressive cerebral white matter (WM) disease associated with rapid clinical decline and is fatal if left untreated.

TSEN54 Gene-Related Pontocerebellar-Hypoplasia and Role of Prenatal MR Imaging: Besides the Common Posterior Fossa Cystic Malformations.

Pontocerebellar-hypoplasia (PCH) related to TSEN54-gene mutation, a rare autosomal recessive disorder, can be associated with three different phenotypes: PCH2A, PCH4 and PCH5. Prenatal imaging features are very scant, in particular for PCH4 and PCH5. The aim of this letter is to illustrate key role of prenatal MR imaging in better evaluation of the cerebellar vermis-hemispheres and pons, which may lead to the differential diagnosis between three PCH TSEN54-related phenotypes already at mid-gestation based on the pattern of the degree of involvement of the vermis and the cerebellar cortex respectively.

Expanding the Molecular Spectrum of Gene Defects in 33 Patients with a Clinical Presentation of KBG Syndrome.

KBG syndrome (KBGS) is a neurodevelopmental disorder caused by the Ankyrin Repeat Domain 11 () haploinsufficiency. Here, we report the molecular investigations performed on a cohort of 33 individuals with KBGS clinical suspicion. By using a multi-testing genomic approach, including gene sequencing, Chromosome Microarray Analysis (CMA), and RT-qPCR gene expression assay, we searched for pathogenic alterations in .

Novel Variant in Exon 3 of the Gene Resulted in Ectopic Posterior Pituitary, Craniocervical Junction Dysmorphism and Limb Anomaly.

. Pituitary differentiation involves a large number of transcription factors. In particular, expression is fundamental for pituitary gland commitment from the ventral diencephalon, suppressing Shh expression in Rathke's pouch.

Successful use of perampanel in GABRA1-related myoclonic epilepsy with photosensitivity.

Pathogenic variants in gamma-aminobutyric acid type A receptor subunit alpha1 (GABRA1) is a protein coding gene that has been associated with a broad phenotypic spectrum of epilepsies. These have ranged from mild generalized forms to early-onset severe epileptic encephalopathies. Both in mild and in severe forms, tonic-clonic and myoclonic seizures with generalized spike and wave discharges and photoparoxysmal responses are common clinical manifestations.

Mucopolysaccharidosis-Plus Syndrome, a Rapidly Progressive Disease: Favorable Impact of a Very Prolonged Steroid Treatment on the Clinical Course in a Child.

Mucopolysaccharidosis-plus syndrome (MPS-PS) is a novel autosomal recessive disorder caused by a mutation in the gene. This syndrome presents with typical symptoms of mucopolysaccharidosis, as well as congenital heart defects, renal, and hematopoietic system disorders. To date, twenty-four patients have been described.

Long-term outcome of consecutive case series of congenital isolated agenesis of corpus callosum.

Objective: To describe the long-term outcome of children with prenatally diagnosed isolated complete agenesis of the corpus callosum (cACC).

Methods: In this single-center case series, we reviewed retrospectively the charts of fetuses referred to our fetal therapy unit from January 2004 to July 2020 for a suspected anomaly of the corpus callosum (CC). Cases with prenatally diagnosed isolated cACC were included.

Progressive Clinical and Neuroradiological Findings in a Child with BCL11B Missense Mutation: Expanding the Phenotypic Spectrum of Related Disorder.

We report a patient affected by -related disorder, providing the first extensive demonstration of clinical and neuroradiological progressive course of the disease, with possible implications on the way it is studied and followed-up. Never described clinical aspects such as toes abnormalities and hypospadias widen the range of dysmorphisms associated with this condition. Our data suggest that mutations may be implicated not only in impaired morphogenesis and hematopoiesis but also in progressive central nervous system damage, which remains to be further investigated and clarified.

Neonatal Diabetes in Patients Affected by Liang-Wang Syndrome Carrying KCNMA1 Variant p.(Gly375Arg) Suggest a Potential Role of Ca and Voltage-Activated K Channel Activity in Human Insulin Secretion.

Liang-Wang syndrome (LIWAS) is a polymalformative syndrome first described in 2019 caused by heterozygous mutation of the KCNMA1 gene encoding the Ca and voltage-activated K channel (BKC). The KCNMA1 variant p.(Gly356Arg) abolishes the function of BKC and blocks the generation of K current.

L1CAM variants cause two distinct imaging phenotypes on fetal MRI.

Data on fetal MRI in L1 syndrome are scarce with relevant implications for parental counseling and surgical planning. We identified two fetal MR imaging patterns in 10 fetuses harboring L1CAM mutations: the first, observed in 9 fetuses was characterized by callosal anomalies, diencephalosynapsis, and a distinct brainstem malformation with diencephalic-mesencephalic junction dysplasia and brainstem kinking. Cerebellar vermis hypoplasia, aqueductal stenosis, obstructive hydrocephalus, and pontine hypoplasia were variably associated.

Autosomal Dominant Hypophosphatemic Rickets: A Case Report and Review of the Literature.

Autosomal dominant hypophosphatemic rickets (ADHR) is an extremely rare form of genetic rickets caused by mutations in the fibroblast growth factor 23 gene. ADHR is characterized by hypophosphatemia secondary to isolated renal phosphate wasting. Only a few cases of ADHR have been reported in the literature to date.

Neonatal Dyshormonogenetic Goiter with Hypothyroidism Associated with Novel Mutations in Thyroglobulin and SLC26A4 Gene.

Congenital goiter is an uncommon cause of neck swelling and it can be associated with hypothyroidism. We discuss a case of primary hypothyroidism with goiter presenting at birth. Ultrasound showed the enlargement of the gland and thyroid function tests detected marked hypothyroidism.