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Lateral meningocele syndrome (LMS) is due to specific pathogenic variants in the last exon of NOTCH3 gene. Besides the lateral meningoceles, this condition presents with dysmorphic features, short stature, congenital heart defects, and feeding difficulties.Here, we report a girl with neurosensorial hearing loss, severe gastroesophageal reflux disease, congenital heart defects, multiple renal cysts, kyphosis and left-convex scoliosis, dysmorphic features, and mild developmental delay. Exome sequencing detected the previously unreported de novo loss-of-function variant in exon 33 of NOTCH3 p.(Lys2137fs). Following the identification of the gene defect, MRI of the brain and spine revealed temporal encephaloceles, inner ears anomalies, multiple spinal lateral meningoceles, and intra-and extra-dural arachnoid spinal cysts. This case illustrates the power of reverse phenotyping to establish clinical diagnosis and expands the spectrum of clinical manifestations related to LMS to include inner ear abnormalities and multi-cystic kidney disease. K E Y W O R D S encephalocele, lateral meningocele syndrome, NOTCH3

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Background and Aims We describe the relationship between overweight and obesity and Hypertension on ABPM. Method We conducted a cross-sectional study using a database of patients aged 6-16 years, who had undergone 24h ABPM from December 2002 through December 2016. ABPM were performed using the validated device Spacelab 90217. Were evaluated the 24h MAP, daytime MAP, nocturnal MAP, systolic and diastolic load, MAP Systolic and Diastolic. Subjects were grouped by BMI Z-score into overweight (>1<2), obese (BMI Z-score >2<3) and severe obese (BMI Z-score >3). A total of 1016 patients were enrolled and recorded n.1210 ABPMs. Obese pts were 202 (19.8%); 126 M;76F;median age 10,2 y. Overweight childrens were 97 (11.9%);52 M;45F;median age 8,4y. Results Among overweight childrens (BMI Z-Score >1<2): 12 (12.3%) had hypertension, 22 (22.6%) pre-hypertension, 15 (15.4%) MH; non dipping pattern was recorded in 26 (52%). 48 were normotensive. Among obese childrens, 122 had hypertension (60.3%): 24 pts had Masked Hypertension (19.6%); 72 (59.0%) had severe ambulatory hypertension with BMI z-score >3 (mean 3.8) ,and in this category all pts were both systolic and diastolic non dipping. 32 (64%) obese with BMI z-score >2, <3 were non-dipping. Diastolic load was significantly higher (p>0,0001) in severe obese. 28 pts had ambulatory prehypertension (13.8%), 11 pts had White Coat Hypertension (4.9%).41 pts had normotension (20.2%). Conclusion The severity of ambulatory hypertension increased with increased BMI Z-score. The non-dipping status is associated, not only with higher BMI Z-score, but was present in overweight and obese with BMI z-score >2<3 also. ABPM is an effective tool that should become routine in all obese patient, but also in overweight childrens, which may lead to better treatments and prevention methods.

Background and Aims Immunoglobulin A Nephropathy (IgAN) is the most common cause of idiopathic glomerulonephritis in paediatric patients. The typical presentation is characterized by recurrent episodes of macroscopic haematuria or persistent microhaematuria with mild or overt proteinuria. Renal function is normally preserved, though a slow progression to chronic kidney disease (CKD) may occur. However, in rare cases IgAN may assume atypical features, presenting with nephrotic syndrome (NS), acute kidney injury (AKI) or assuming the characteristic of a rapidly progressive glomerulonephritis, leading to significant difficulties in management and critical impact on prognosis. Method Of total 756 renal biopsies performed in our centre from 2000 till 2019, 174 (23%) diagnosis of IgA nephropathy were made: 123 (70,6%) of 174 with a milder histological stage (I or II according to Lee’s) and 51 (29,3%) with severe stages (III-IV). Clinical onset of these 51 patients was mostly characterized by a nephritic syndrome with micro-macrohaematuria, though in 7 of them it assumed atypical features (table 1). Results Patients 1, 2, 3 and 4 showed a rapidly progressive IgAN with extensive crescentic lesions at histological evaluation. In all of the four patients the onset of the disease was characterised by a compromised renal function, thought, according to the medical history, in patients 2 and 4 clinical signs of nephropathy had started some months before the first medical evaluation. This detail, considering the poorer clinical outcome of patients 2 and 4 (table 1), strongly highlights the need of promptness in the treatment of these conditions. Patient 1 achieved a complete remission after steroid pulse therapy (Pozzi scheme), while for patients 2,3,4 an additional immunosuppressive treatment was required. The nephropathy of patient 5 was, instead, characterized by AKI with consistent macrohaematuria. Interestingly, the severity of the clinical presentation was not related to the glomerular lesion (the histology showed a minimal change disease), rather to the intra-tubular haemorrhage, causing an obstructive acute kidney injury. Patient 5 achieved a complete remission after steroid treatment. The onset of IgAN in patients 6 and 7 was characterized by a nephrotic syndrome, which is a very uncommon feature (<2% of all IgAN). Patient 6, who showed a massive proteinuria (till 11 grams/24 hours) was promptly treated with steroid and tacrolimus, achieving a complete remission in 6 moths. Patient 7, a sri-lankan girl, was diagnosed in 2008 in Sri-Lanka. She underwent treatment with steroid and Mycophenolate and successively, for the persistence of proteinuria, with Cyclosporine A. From 2014 she has been followed by our centre. Despite a second cycle with Cyclosporine she has shown a persistence of proteinuria and a slow progression to CKD. Conclusion This study highlights that a typical disease like IgAN may hide behind an atypical and severe presentation. Moreover, the blackboard of the atypical forms is extremely heterogeneous, stretching from NS to crescentic and progressive diseases. As a consequence, the treatment of these conditions is not codified and represents an important challenge for the clinician. This calls for multicentric studies which could provide shared recommendation for the management of these atypical forms of IgAN.