Clinical Variability of Shashi-Pena Syndrome: A Novel Variant Associated with Overgrowth and Minor Neurodevelopmental Features.

Introduction: Shashi-Pena syndrome (SHAPNS) is a rare congenital disorder characterized by macrocephaly, delayed psychomotor development with intellectual disability, hypotonia, seizures, episodic hypoglycemia, distinct facial features, and glabellar nevus flammeus, caused by heterozygous variants of the gene.

Case Presentation: We report on a 15-year-old patient in care at our hospital since the age of 4 years presenting with minor neurodevelopmental problems, marked postnatal overgrowth without advanced bone age, and dental anomalies.

Conclusion: Patients described in the literature with SHAPNS are reported indicating a broad spectrum of clinical manifestations.

Copy Number Variants in Cardiac Channelopathies: Still a Missed Part in Routine Arrhythmic Diagnostics.

Inherited cardiac channelopathies are major causes of sudden cardiac death (SCD) in young people. Genetic testing is focused on the identification of single-nucleotide variants (SNVs) by Next-Generation Sequencing (NGS). However, genetically elusive cases can carry copy number variants (CNVs), which need specific detection tools.

Epidemiological characterization of SARS-CoV-2 variants in children over the four COVID-19 waves and correlation with clinical presentation.

Since the start of SARS-CoV-2 pandemic, children aged ≤ 12 years have always been defined as underrepresented in terms of SARS-CoV-2 infections' frequency and severity. By correlating SARS-CoV-2 transmission dynamics with clinical and virological features in 612 SARS-CoV-2 positive patients aged ≤ 12 years, we demonstrated a sizeable circulation of different SARS-CoV-2 lineages over the four pandemic waves in paediatric population, sustained by local transmission chains. Age < 5 years, highest viral load, gamma and delta clades positively influence this local transmission.

Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic Lymphohistiocytosis.

We describe a 2 year old boy with two previously undescribed frameshift mutations in the interferon (IFN)α/β receptor 2 () gene presenting with hemophagocytic lymphohistiocytosis (HLH) following measles-mumps-rubella vaccination. Functional analyses show the absence of response to type I IFN in the patient's cells, as revealed by the lack of phosphorylation of STAT1 and the lack of induction of interferon-stimulated genes upon stimulation with IFNα. HLH has been reported in patients with inborn errors of type I IFN-mediated immune responses following vaccination with live-attenuated viruses.

TUBB3 E410K syndrome: Case report and review of the clinical spectrum of TUBB3 mutations.

The tubulinopathies refer to a wide range of brain malformations caused by mutations in one of the seven genes encoding different tubulin's isotypes. The β-tubulin isotype III (TUBB3) gene has a primary function in nervous system development and axon generation and maintenance, due to its neuron-specific expression pattern. A recurrent heterozygous mutation, c.

p.Arg1809Cys substitution in neurofibromin is associated with a distinctive NF1 phenotype without neurofibromas.

Analysis of 786 NF1 mutation-positive subjects with clinical diagnosis of neurofibromatosis type 1 (NF1) allowed to identify the heterozygous c.5425C>T missense variant (p.Arg1809Cys) in six (0.

Familial spinal neurofibromatosis due to a multiexonic NF1 gene deletion.

We report the detailed clinical presentation and molecular features of a spinal neurofibromatosis familial case where a 40-year-old woman, presenting with multiple bilateral spinal neurofibromas and no other clinical feature of neurofibromatosis type 1 (NF1), inherited a paternal large multiexonic deletion (c.5944-?_7126+?del) which resulted in NF1 gene haploinsufficiency at the RNA level. In the clinically unaffected 73-year-old father, spinal cord MRI disclosed bilateral and symmetrical hypertrophy of spinal lumbosacral roots.

Germline mosaicism in neurofibromatosis type 1 due to a paternally derived multi-exon deletion.

We report on the clinical and molecular features of a family in which neurofibromatosis type 1 (NF1) occurred in two of three siblings born to unaffected parents and in one granddaughter. Linkage analysis showed that the two affected siblings and the daughter of one of them shared the same paternal allele, whereas they had inherited different maternal alleles. We detected a disease-causing deletion (c.