A deep phenotyping experience: up to date in management and diagnosis of Malan syndrome in a single center surveillance report

Background Malan syndrome (MALNS) is a recently described ultrarare syndrome lacking guidelines for diagnosis, management and monitoring of evolutive complications. Less than 90 patients are reported in the literature and limited clinical information are available to assure a proper health surveillance. Results A multidisciplinary team with high expertise in MALNS has been launched at the "Ospedale Pediatrico Bambino Gesu", Rome, Italy. Sixteen Italian MALNS individuals with molecular confirmed clinical diagnosis of MALNS were enrolled in the program. For all patients, 1-year surveillance in a dedicated outpatient Clinic was attained. The expert panel group enrolled 16 patients and performed a deep phenotyping analysis directed to clinically profiling the disorder and performing critical revision of previously reported individuals. Some evolutive complications were also assessed. Previously unappreciated features (e.g., high risk of bone fractures in childhood, neurological/neurovegetative symptoms, noise sensitivity and Chiari malformation type 1) requiring active surveillance were identified. A second case of neoplasm was recorded. No major cardiovascular anomalies were noticed. An accurate clinical description of 9 new MALNS cases was provided. Conclusions Deep phenotyping has provided a more accurate characterization of the main clinical features of MALNS and allows broadening the spectrum of disease. A minimal dataset of clinical evaluations and follow-up timeline has been proposed for proper management of patients affected by this ultrarare disorder

Performance metrics of the scoring system for the diagnosis of the beckwith–wiedemann spectrum (bwsp) and its correlation with cancer development

Different scoring systems for the clinical diagnosis of the Beckwith–Wiedemann spectrum (BWSp) have been developed over time, the most recent being the international consensus score. Here we try to validate and provide data on the performance metrics of these scoring systems of the 2018 international consensus and the previous ones, relating them to BWSp features, molecular tests, and the probability of cancer development in a cohort of 831 patients. The consensus scoring system had the best performance (sensitivity 0.85 and specificity 0.43). In our cohort, the diagnostic yield of tests on blood-extracted DNA was low in patients with a low consensus score (~20% with a score = 2), and the score did not correlate with cancer development. We observed hepatoblastoma (HB) in 4.3% of patients with UPD(11)pat and Wilms tumor in 1.9% of patients with isolated lateralized overgrowth (ILO). We validated the efficacy of the currently used consensus score for BWSp clinical diagnosis. Based on our observation, a first-tier analysis of tissue-extracted DNA in patients with <4 points may be considered. We discourage the use of the consensus score value as an indicator of the probability of cancer development. Moreover, we suggest considering cancer screening for negative patients with ILO (risk ~2%) and HB screening for patients with UPD(11)pat (risk ~4%)

Nomenclature and definition in asymmetric regional body overgrowth

We designate a novel term “isolated lateralized overgrowth” (ILO) for the findings previously described as “isolated hemihypertrophy” and “isolated hemihyperplasia.” ILO is defined as lateralized overgrowth in the absence of a recognized pattern of malformations, dysplasia, or morphologic variants. ILO is likely genetically heterogeneous. Further study is required to determine more of the underlying genetic etiologies and potential associations with currently unrecognized patterns of malformation.National Cancer Institute, Grant number: K08CA193915; Alex’s Lemonade Stand Foundationfor Childhood Cancer; St. Baldrick’s Foundatio

Fast preamplifier for time-of-flight silicon strip detectors operating in the temperature range from 20°C to -55°C

A fast preamplifier for time-of-flight measurements has been constructed and operated at low temperature (−55°C). The design criteria and performance tests are presented. The measured rise time with a silicon strip detector with a capacitance of 15 pF is 3.2 ns. This preamplifier is employed in a cold silicon strip time-of-flight apparatus which has a time resolution of 120±6 ps at −55°C for minimum ionizing particles of unitary charge

Performance of a time-of-flight silicon strip telescope in the temperature range 20°C to -55°C

A cold silicon strip telescope for time-of-flight determination at −55°C has been tested using a hadron beam at Saturne II. Saclay. We present performance tests of the telescope, the time-of-flight distributions between pairs of silicon hodoscopes and their dependence on temperature. A detailed description of the apparatus, the refrigerator system and the calibration procedures is also reported. A linear relationships between the time resolution and the temperature of the apparatus is measured. An improvement of a factor 2 in the time-of-flight resolution is observed when the temperature decreases from +20°C to −55°

Seasonal and pandemic influenza vaccine: recommendations to families of at-risk children during the 2009-10 season

We performed a study in three Italian regions to evaluate the association between provided recommendations and immunization uptake of the two influenza vaccines in children with chronic diseases. We interviewed families of 119 at-risk children, collecting information regarding recommendations and immunizations against pandemic and seasonal influenza. In total 60.5% of children had received seasonal influenza vaccine, 38.7% had received pandemic influenza vaccine and 33.6% had not been vaccinated. The majority of immunized children had received specific recommendations by a physician. Physicians involved in the management of children with chronic diseases should actively recommend influenza immunization

GH EXCESS IN CHILDREN WITH OPG AND NF1: A SINGLE INSTITUTION EXPERIENCE

Optic pathway gliomas (OPGs) are low-grade tumors often arising in the context of Neurofibromatosis 1 (NF1). NF1 can be associated with a dysre- gulation of Growth Hormone (GH) secretion: whereas a deficiency is well known, the occurrence of GH excess is exceedingly rare and mostly involves children with OPGs. We describe GH excess in a cohort of patients referred to our institution for OPG. Children diagnosed with OPG were evaluated for height, height-velocity and pubertal status. When height velocity was .2 SDS, FT4, TSH, prolactin basal levels, IGF-1, GH levels after oral glucose tolerance tests (OGTT) and bone age were assessed. If precocious puberty was evident, LH and sex steroid hormone levels were tested. Children with a confirmed GH excess (lack of GH suppressibility to ,1.0 ng/mL during OGTT) were treated with GH inhibitor lanreotide. From January to December 2013, 37 children (median age 110 months; F/M 19/18) were screened. Thirty-four patients (92%) had NF1, seven of which (19%) showed a pathologic GH secretion (median IGF1 390 ng/ml). Median height was 2.96 SDS and all children showed normal levels of FT4, TSH, prolactin. One child was already being treated for precocious puberty with complete clinical and biochemical control and 3 were receiving chemother- apy according to SIOP LGG 2004 protocol. Lanreotide was started in 3 chil- dren obtaining the normalization of IGF-1 levels with no major adverse events. Disease assessments after 6-12 months showed clinical and radio- logical stability in all the patients; notably, one of them had previously shown persistent progression despite chemotherapy. Our pilot study suggests that pathologic GH secretion in children with OPG and NF1 could be more frequent than previously reported. Treatment with lanreotide was well toler- ated and effective at reducing GH secretion, an effect that might improve tumor control. Larger cohort and longer follow-up are required to draw firm conclusions

Ligneous periodontal lesions in a young child with severe plasminogen deficiency: a case report

BACKGROUND: Ligneous periodontitis or gingivitis is a rare periodontal disorder, secondary to plasminogen deficiency, characterised by nodular gingival enlargements and progressive destructive membranous periodontal disease. CASE REPORT: We describe the early and successful dental management of a case of ligneous gingivitis secondary to plasminogen deficiency in a 6-year- old girl. The patient was referred because of a nodular asymptomatic gingival hypertrophy with ulceration around the eruption site of tooth 36, without any detectable tooth mobility. After non-surgical management of the lesion and strict follow-up, the first molar erupted completely, with no signs of bone and periodontal disease. CONCLUSION: Ulcerated periodontal lesions could represent the ?rst signs of plasminogen deficiency. The early treatment is essential in preventing infections and the onset of a destructive periodontitis. The paediatric dentist may play a key role in early diagnosis and treatment

Temperature dependence of time resolution and electronic noise in a silicon detector telescope

We have constructed a silicon detector time-of-flight spectrometer operating at low temperature with an overall time resolution of 115.2 ± 2.0 ps at −50°C for minimum ionizing particles with unitary charge. We report the measurement of the overall time resolution of the telescope versus temperature in several relevant experimental conditions from −50 to 20°C. An extensive experimental study of the noise components of the detector and of the electronic readout as a function of the temperature is also given. We present an analysis of the measured noise components in order to account for the improvement of time resolution when the temperature varies from 20 to −50°C. Future developments of cold silicon strip detectors for time-of-flight determination are considered