Intrafamilial variability in SPTAN1-related disorder: From benign convulsions with mild gastroenteritis to developmental encephalopathy

Mutations in SPTAN1 gene are responsible for a wide spectrum of neurodevelopmental disorders including early-onset epileptic encephalopathy with progressive brain atrophy, severe intellectual disability with cerebellar malformations, and relatively milder phenotypes with or without epilepsy. Herein, we report three affected individuals including two siblings of 13 and 8 years and their 39-year-old mother, carrying a novel pathogenic variant in SPTAN1 gene. The phenotype of the index cases and their mother was remarkable for the variable expressivity, including benign convulsions with mild gastroenteritis, intellectual disability and developmental encephalopathy with epilepsy. Our clinical observation suggests for the first time that variants in SPTAN1 gene might be involved in the aetiology of benign convulsions correlated with mild gastroenteritis

A novel SHANK3 interstitial microdeletion in a family with intellectual disability and brain MRI abnormalities resembling Unidentified Bright Objects.

Background SHANK3 mutations are responsible for Phelan-McDermid syndrome but they are also associated with autism and/or intellectual disability. Case report We report a family with four affected individuals including the 37 year-old mother, her 12 year-old male monozygotic twins and 8 year-old daughter harboring a novel SHANK3 interstitial microdeletion. All four members presented with intellectual disability of variable severity. The twins showed brain abnormalities similar to Unidentified Bright Objects (UBOs), typically detected in patients with Neurofibromatosis type 1 (NF1), but they did not display causative mutations in NF1 gene. Conclusion To date, this is the first report of an affected individual with SHANK3 interstitial deletion able to reproduce. Moreover, we found a previously unreported possible association between SHANK3 deletion and UBOs-like lesions in the brai

A novel SHANK3 interstitial microdeletion in a family with intellectual disability and brain MRI abnormalities resembling Unidentified Bright Objects

Background SHANK3 mutations are responsible for Phelan-McDermid syndrome but they are also associated with autism and/or intellectual disability. Case report We report a family with four affected individuals including the 37 year-old mother, her 12 year-old male monozygotic twins and 8 year-old daughter harboring a novel SHANK3 interstitial microdeletion. All four members presented with intellectual disability of variable severity. The twins showed brain abnormalities similar to Unidentified Bright Objects (UBOs), typically detected in patients with Neurofibromatosis type 1 (NF1), but they did not display causative mutations in NF1 gene. Conclusion To date, this is the first report of an affected individual with SHANK3 interstitial deletion able to reproduce. Moreover, we found a previously unreported possible association between SHANK3 deletion and UBOs-like lesions in the brain

Modeling the polar motion of Titan

The angular momentum of the atmosphere and of the hydrocarbon lakes of Titan have a large equatorial component that can excite polar motion, a variable orientation of the rotation axis of Titan with respect to its surface. We here use the angular momentum obtained from a General Circulation Model of the atmosphere of Titan and from an Ocean Circulation Model for Titan's polar lakes to model the polar motion of Titan as a function of the interior structure. Besides the gravitational torque exerted by Saturn on Titan's aspherical mass distribution, the rotational model also includes torques arising due to the presence of an ocean under a thin ice shell as well as the influence of the elasticity of the different layers. The Chandler wobble period of a solid and rigid Titan without its atmosphere is about 279 years. The period of the Chandler wobble is mainly influenced by the atmosphere of Titan (-166 years) and the presence of an internal global ocean (+135 to 295 years depending on the internal model) and to a lesser extent by the elastic deformations (+3.7 years). The forced polar motion of a solid and rigid Titan is elliptical with an amplitude of about 50 m and a main period equal to the orbital period of Saturn. It is mainly forced by the atmosphere of Titan while the lakes of Titan are at the origin of a displacement of the mean polar motion, or polar offset. The subsurface ocean can largely increase the polar motion amplitude due to resonant amplification with a wobble free mode of Titan. The amplitudes as well as the main periods of the polar motion depend on whether and which forcing period is close to the period of a free mode. For a thick ice shell, the polar motion mainly has an annual period and an amplitude of about 1 km. For thinner ice shells, the polar motion amplitude can reach several tens of km and shorter periods become dominant. We demonstrate that for thick ice shells, the ice shell rigidity weakly influences the amplitude of the polar motion. For thin ice shells, the level of the resonant amplification of the polar motion amplitude depends on the ice shell rigidity. Future observations of the polar motion of Titan could help constraining some properties of its interior structure as the ice shell thickness and ocean density

Corpus callosum abnormalities: neuroimaging, cytogenetics and clinical characterization of a very large multicenter Italian series

Corpus callosum abnormalities (CCA) have an estimated prevalence ranging from 0.3% up to 0.7% in patients undergoing brain imaging. CCA can be identified incidentally, or can be part of a developmental disease. We performed a retrospective study of 551 patients, identified non-syndromic (NS) CCA and syndromic (S) CCA, reviewing clinical features, neuroradiological aspects, genetic etiology, and chromosomal microarray (CMA) results. Syndromic CCA subjects were prevalent (60%) and they showed the most severe clinical features. Cortical malformations and cerebellar anomalies were 23% of cerebral malformation associated to CCA (plus), 23 and 14% respectively in syndromic forms. A clinical and/or genetic diagnosis was obtained in 37% of syndromic CCA including chromosomal rearrangements on high-resolution karyotype (18%), microdeletion/microduplication syndromes (31%) and monogenic diseases (51%). Non-syndromic CCA anomalies had mildest clinical features, although intellectual disability was present in 49% of cases and epilepsy in 13%. CMA diagnostic rate in our cohort of patients ranged from 11 to 23% (NS to S). A high percentage of patients (76% 422/551) remain without a diagnosis. Combined high resolution CMA studies and next-generation sequencing (NGS) strategies will increase the probability to identify new causative genes of CCA and to redefine genotype–phenotype correlation