The mechanics of the collateral ligaments in the metacarpophalangeal joints: A scoping review.

Background: The metacarpophalangeal (MCP) joint's collateral ligaments have been extensively debated, with no clear consensus on their mechanics. Understanding their function is crucial for comprehending joint movement and stability.

Methods: A thorough search was conducted across databases, including PubMed, Scopus, Cochrane library and grey literature.

Clinical profiling of MRD48 and functional characterization of two novel pathogenic RAC1 variants.

RAC1 is a member of the Rac/Rho GTPase subfamily within the RAS superfamily of small GTP-binding proteins, comprising 3 paralogs playing a critical role in actin cytoskeleton remodeling, cell migration, proliferation and differentiation. De novo missense variants in RAC1 are associated with a rare neurodevelopmental disorder (MRD48) characterized by DD/ID and brain abnormalities coupled with a wide range of additional features. Structural and functional studies have documented either a dominant negative or constitutively active behavior for a subset of mutations.

Dominant ARF3 variants disrupt Golgi integrity and cause a neurodevelopmental disorder recapitulated in zebrafish.

Vesicle biogenesis, trafficking and signaling via Endoplasmic reticulum-Golgi network support essential developmental processes and their disruption lead to neurodevelopmental disorders and neurodegeneration. We report that de novo missense variants in ARF3, encoding a small GTPase regulating Golgi dynamics, cause a developmental disease in humans impairing nervous system and skeletal formation. Microcephaly-associated ARF3 variants affect residues within the guanine nucleotide binding pocket and variably perturb protein stability and GTP/GDP binding.

Prevalence of bladder cancer in Costello syndrome: New insights to drive clinical decision-making.

Costello syndrome (CS) is a rare disorder affecting development and growth characterized by cancer predisposition and caused by mutations in HRAS proto-oncogene. Somatic HRAS mutations drive bladder carcinogenesis. The aim of this study was to analyze prevalence and histological characterization of bladder cancer (BC) in a cohort of patients with CS to help clinicians plan effective management strategies.

SPRED2 loss-of-function causes a recessive Noonan syndrome-like phenotype.

Upregulated signal flow through RAS and the mitogen-associated protein kinase (MAPK) cascade is the unifying mechanistic theme of the RASopathies, a family of disorders affecting development and growth. Pathogenic variants in more than 20 genes have been causally linked to RASopathies, the majority having a dominant role in promoting enhanced signaling. Here, we report that SPRED2 loss of function is causally linked to a recessive phenotype evocative of Noonan syndrome.

Co-Occurring Heterozygous and Truncating Variants: Unusual Presentation and Refinement of the IDDSADF Phenotype.

, the application of genomic sequencing in clinical practice has allowed us to appreciate the contribution of co-occurring pathogenic variants to complex and unclassified clinical phenotypes. Besides the clinical relevance, these findings have provided evidence of previously unrecognized functional links between genes in the context of developmental processes and physiology. , a 5-year-old patient showing an unclassified phenotype characterized by developmental delay, speech delay, peculiar behavioral features, facial dysmorphism and severe cardiopathy was analyzed by trio-based whole exome sequencing (WES) analysis to identify the genomic events underlying the condition.

Broadening the phenotypic spectrum of Beta3GalT6-associated phenotypes.

Biallelic mutations in B3GALT6, coding for a galactosyltransferase involved in the synthesis of glycosaminoglycans (GAGs), have been associated with various clinical conditions, causing spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1 or SEMDJL Beighton type), Al-Gazali syndrome (ALGAZ), and a severe progeroid form of Ehlers-Danlos syndrome (EDSSPD2). In the 2017 Ehlers-Danlos syndrome (EDS) classification, Beta3GalT6-related disorders were grouped in the spondylodysplastic EDSs together with spondylodysplastic EDSs due to B4GALT7 and SLC39A13 mutations. Herein, we describe a patient with a previously unreported homozygous pathogenic B3GALT6 variant resulting in a complex phenotype more severe than spondyloepimetaphyseal dysplasia with joint laxity type 1, and having dural ectasia and aortic dilation as additionally associated features, further broadening the phenotypic spectrum of the Beta3GalT6-related syndromes.

SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females.

Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms.

When to test fetuses for RASopathies? Proposition from a systematic analysis of 352 multicenter cases and a postnatal cohort.

Purpose: Recent studies have identified suggestive prenatal features of RASopathies (e.g., increased nuchal translucency [NT], cystic hygroma [CH], hydrops, effusions, congenital heart diseases [CHD], polyhydramnios, renal anomalies).

Vascularized bone grafts for post-traumatic defects in the upper extremity.

Vascularized bone grafts (VBGs) are widely employed to reconstruct upper extremity bone defects. Conventional bone grafting is generally used to treat defects smaller than 5-6 cm, when tissue vascularization is adequate and there is no infection risk. Vascularized fibular grafts (VFGs) are mainly used in the humerus, radius or ulna in cases of persistent non-union where traditional bone grafting has failed or for bone defects larger than 6 cm.

De Novo VPS4A Mutations Cause Multisystem Disease with Abnormal Neurodevelopment.

The endosomal sorting complexes required for transport (ESCRTs) are essential for multiple membrane modeling and membrane-independent cellular processes. Here we describe six unrelated individuals with de novo missense variants affecting the ATPase domain of VPS4A, a critical enzyme regulating ESCRT function. Probands had structural brain abnormalities, severe neurodevelopmental delay, cataracts, growth impairment, and anemia.

Enhanced MAPK1 Function Causes a Neurodevelopmental Disorder within the RASopathy Clinical Spectrum.

Signal transduction through the RAF-MEK-ERK pathway, the first described mitogen-associated protein kinase (MAPK) cascade, mediates multiple cellular processes and participates in early and late developmental programs. Aberrant signaling through this cascade contributes to oncogenesis and underlies the RASopathies, a family of cancer-prone disorders. Here, we report that de novo missense variants in MAPK1, encoding the mitogen-activated protein kinase 1 (i.