Neurological phenotype of mowat-wilson syndrome

Mowat-Wilson Syndrome (MWS) (OMIM # 235730) is a rare disorder due to ZEB2 gene defects (heterozygous mutation or deletion). The ZEB2 gene is a widely expressed regulatory gene, extremely important for the proper prenatal development. MWS is characterized by a specific facial gestalt and multiple musculoskeletal, cardiac, gastrointestinal, and urogenital anomalies. The nervous system involvement is extensive and constitutes one of the main features in MWS, heavily affecting prognosis and life quality of affected individuals. This review aims to comprehensively organize and discuss the neurological and neurodevelopmental phenotype of MWS. First, we will describe the role of ZEB2 in the formation and development of the nervous system by reviewing the preclinical studies in this regard. ZEB2 regulates the neural crest cell differentiation and migration, as well as in the modulation of GABAergic transmission. This leads to different degrees of structural and functional impairment that have been explored and deepened by various authors over the years. Subsequently, the different neurological aspects of MWS (head and brain malformations, epilepsy, sleep disorders, and enteric and peripheral nervous system involvement, as well as developmental, cognitive, and behavioral features) will be faced one at a time and extensively examined from both a clinical and etiopathogenetic point of view, linking them to the ZEB2 related pathways

Experimental validation of a subject-specific finite element model of lumbar spine segment using digital image correlation

Pathologies such as cancer metastasis and osteoporosis strongly affect the mechanical properties of the vertebral bone and increase the risk of fragility fractures. The prediction of the fracture risk with a patient-specific model, directly generated from the diagnostic images of the patient, could help the clinician in the choice of the correct therapy to follow. But before such models can be used to support any clinical decision, their credibility must be demonstrated through verification, validation, and uncertainty quantification. In this study we describe a procedure for the generation of such patient-specific finite element models and present a first validation of the kinematics of the spine segment. Quantitative computed tomography images of a cadaveric lumbar spine segment presenting vertebral metastatic lesions were used to generate the model. The applied boundary conditions replicated a specific experimental test where the spine segment was loaded in compression-flexion. Model predictions in terms of vertebral surface displacements were compared against the full-field experimental displacements measured with Digital Image Correlation. A good agreement was obtained from the local comparison between experimental data and simulation results (R2 > 0.9 and RMSE% <8%). In conclusion, this work demonstrates the possibility to apply the developed modelling pipeline to predict the displacement field of human spine segment under physiological loading conditions, which is a first fundamental step in the credibility assessment of these clinical decision-support technology

Oral manifestation of Goltz-Gorlin syndrome in a young girl

Introduction Focal dermal hypoplasia (Goltz-Gorlin syndrome) is a multi-system disorder characterized by involvement of skin, skeletal system, eyes and face. It is caused by loss-of-function mutations in the PORCN gene. We report the case of a young female, focusing on the dental features. Aim To describe the oral manifestation of a rare disorder that resembles ectodermal dysplasia (ED). Case report Clinical, radiological and genetic findings revealed common features of Goltz-Gorlin syndrome and pure ED. Oro-dental characteristics of the patient mostly corresponded to those described in the literature. However, previously unreported oro-dental findings such as taurodontism, peg-shaped teeth and microdontia are considered unusual for Goltz-Gorlin syndrome, but similar to the dental features of hypohidrotic ED. Clinical characterization of the patient by a multidisciplinary approach is described and a comprehensive review of the literature is presented

Computing the absorption and emission spectra of 5-methylcytidine in different solvents: a test-case for different solvation models

International audience; The optical spectra of 5-methylcytidine in three different solvents (tetrahydrofuran, acetonitrile, and water) is measured, showing that both the absorption and the emission maximum in water are significantly blue-shifted (0.08 eV). The absorption spectra are simulated based on CAM-B3LYP/TD-DFT calculations but including solvent effects with three different approaches: (i) a hybrid implicit/explicit full quantum mechanical approach, (ii) a mixed QM/MM static approach, and (iii) a QM/MM method exploiting the structures issuing from molecular dynamics classical simulations. Ab-initio Molecular dynamics simulations based on CAM-B3LYP functionals have also been performed. The adopted approaches all reproduce the main features of the experimental spectra, giving insights on the chemical−physical effects responsible for the solvent shifts in the spectra of 5-methylcytidine and providing the basis for discussing advantages and limitations of the adopted solvation models

Renormalization--Group Solutions for Yukawa Potential

The self--similar renormalization group is used to obtain expressions for the spectrum of the Hamiltonian with the Yukawa potential. The critical screening parameter above which there are no bound states is also obtained by this method. The approach presented illustrates that one can achieve good accuracy without involving extensive numerical calculations, but invoking instead the renormalization--group techniques.Comment: 1 file, 12 pages, RevTe

Ten-Year Longitudinal Study of Thyroid Function in Children with Down's Syndrome

Background/Aims: The natural history of thyroid function in children with Down's syndrome is relatively unknown. We hypothesized that in these patients the occurrence of thyroid dysfunction rises during development. Methods: Thyroid function was assessed yearly in 145 children with Down's syndrome, all followed from birth up to 10 years of age. Heteroskedastic binary and ordinary logistic regression for repeated measures was used to evaluate the relationship of thyroid function with continuous time. Results: Congenital hypothyroidism was detected in 7% of cases. The probability of acquired thyroid dysfunction increased from 30% at birth to 49% at 10 years (p < 0.001). The subclinical hypothyroidism was nearly stable during the follow-up. The probability of hypothyroidism increased from 7 to 24% at 10 years (p < 0.001). Positive anti-thyroglobulin antibodies were associated with higher odds of more severe hypothyroidism (odds ratio 3.6). Positive anti-thyroid peroxidase antibodies were a better predictor of more severe hypothyroidism (odds ratio 6.1). Diffuse hypoechogenicity on thyroid ultrasound was found in 34 out of 145 children. Conclusion: The probability of thyroid dysfunction increasing during development is higher than previously reported. Such children should be carefully monitored annually to early identify thyroid dysfunction

Clinical and molecular characterization of 40 patients with classic Ehlers--Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations.

Classic Ehlers-Danlos syndrome (cEDS) is a rare autosomal dominant connective tissue disorder that is primarily characterized by skin hyperextensibility, abnormal wound healing/atrophic scars, and joint hypermobility. A recent study demonstrated that more than 90% of patients who satisfy all of these major criteria harbor a type V collagen (COLLV) defect. This cohort included 40 patients with cEDS who were clinically diagnosed according to the Villefranche nosology. The flowchart that was adopted for mutation detection consisted of sequencing the COL5A1 gene and, if no mutation was detected, COL5A2 analysis. In the negative patients the presence of large genomic rearrangements in COL5A1 was investigated using MLPA, and positive results were confirmed via SNP-array analysis. We report the clinical and molecular characterization of 40 patients from 28 families, consisting of 14 pediatric patients and 26 adults. A family history of cEDS was present in 9 patients. The majority of the patients fulfilled all the major diagnostic criteria for cEDS; atrophic scars were absent in 2 females, skin hyperextensibility was not detected in a male and joint hypermobility was negative in 8 patients (20% of the entire cohort). Wide inter- and intra-familial phenotypic heterogeneity was observed. We identified causal mutations with a detection rate of approximately 93%. In 25/28 probands, COL5A1 or COL5A2 mutations were detected. Twenty-one mutations were in the COL5A1 gene, 18 of which were novel (2 recurrent). Of these, 16 mutations led to nonsense-mediated mRNA decay (NMD) and to COLLV haploinsufficiency and 5 mutations were structural. Two novel COL5A2 splice mutations were detected in patients with the most severe phenotypes. The known p. (Arg312Cys) mutation in the COL1A1 gene was identified in one patient with vascular-like cEDS. Our findings highlight that the three major criteria for cEDS are useful and sufficient for cEDS clinical diagnosis in the large majority of the patients. The borderline patients for whom these criteria fail can be diagnosed when minor signs of connective tissue diseases and family history are present and when genetic testing reveals a defect in COLLV. Our data also confirm that COL5A1 and COL5A2 are the major, if not the only, genes involved in cEDS

Multiple sulfatase deficiency with neonatal manifestation.

Multiple Sulfatase Deficiency (MSD; OMIM 272200) is a rare autosomal recessive inborn error of metabolism caused by mutations in the sulfatase modifying factor 1 gene, encoding the formylglycine-generating enzyme (FGE), and resulting in tissue accumulation of sulfatides, sulphated glycosaminoglycans, sphingolipids and steroid sulfates. Less than 50 cases have been published so far. We report a new case of MSD presenting in the newborn period with hypotonia, apnoea, cyanosis and rolling eyes, hepato-splenomegaly and deafness. This patient was compound heterozygous for two so far undescribed SUMF1 mutations (c.191C &gt; A; p.S64X and c.818A &gt; G; p.D273G)