Constitutional chromothripsis involving the critical region of 9q21.13 microdeletion syndrome

BACKGROUND: The chromothripsis is a biological phenomenon, first observed in tumors and then rapidly described in congenital disorders. The principle of the chromothripsis process is the occurrence of a local shattering to pieces and rebuilding of chromosomes in a random order. Congenital chromothripsis rearrangements often involve reciprocal rearrangements on multiple chromosomes and have been described as cause of contiguous gene syndromes. We hypothesize that chromothripsis could be responsible for known 9q21.13 microdeletion syndrome, causing a composite phenotype with additional features. CASE PRESENTATION: The case reported is a 16- years-old female with a complex genomic rearrangement of chromosome 9 including the critical region of 9q21.13 microdeletion syndrome. The patient presents with platelet disorder and thyroid dysfunction in addition to the classical neurobehavioral phenotype of the syndrome. CONCLUSIONS: The presence of multiple rearrangements on the same chromosome 9 and the rebuilding of chromosome in a random order suggested that the rearrangement could origin from an event of chromthripsis. To our knowledge this is the first report of congenital chromothripsis involving chromosome 9. Furthermore this is the only case of 9q21.13 microdeletion syndrome due to chromothripsis

New insights in the interpretation of array-CGH: Autism spectrum disorder and positive family history for intellectual disability predict the detection of pathogenic variants

BACKGROUND: Array-CGH (aCGH) is presently used into routine clinical practice for diagnosis of patients with intellectual disability (ID), multiple congenital anomalies (MCA), and autism spectrum disorder (ASD). ACGH could detect small chromosomal imbalances, copy number variations (CNVs), and closely define their size and gene content. ACGH detects pathogenic imbalances in 14-20 % of patients with ID. The aims of this study were: to establish clinical clues potentially associated with pathogenic CNVs and to identify cytogenetic indicators to predict the pathogenicity of the variants of uncertain significance (VOUS) in a large cohort of paediatric patients. METHODS: We enrolled 214 patients referred for either: ID, and/or ASD and/or MCA to genetic services at the Federico II University of Naples, Department of Translational Medicine. For each patient we collected clinical and imaging data. All the patients were tested with aCGH or as first-tier test or as part of a wider diagnostic work-up. RESULTS: Pathologic data were detected in 65 individuals (30 %) and 46 CNVs revealed a known syndrome. The pathological CNVs were usually deletions showing the highest gene-dosage content. The positive family history for ID/ASD/MCA and ASD were good indicators for detecting pathological chromosomal rearrangements. Other clinical features as eyes anomalies, hearing loss, neurological signs, cutaneous dyscromia and endocrinological problems seem to be potential predictors of pathological CNVs. Among patients carrying VOUS we analyzed genetic features including CNVs size, presence of deletion or duplication, genic density, multiple CNVs, to clinical features. Higher gene density was found in patients affected by ID. This result suggest that higher gene content has more chances to include pathogenic gene involved and causing ID in these patients. CONCLUSION: Our study suggest the use of aCGH as first-tier test in patients with neurdevelopmental phenotypes. The inferred results have been used for building a flow-chart to be applied for children with ID

A comparison of laser with radiofrequency ablation for the treatment of benign thyroid nodules: a propensity score matching analysis

reserved18Purpose: To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules.Materials and methods: Institutional review board approval was obtained, and patients' consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 5714years) with LA and 152 (107 females, age 5714years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12months and complications were evaluated.Results: No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12months was -67 +/- 19% vs. -57 +/- 21% (p<0.001)-70 +/- 19% vs. -62 +/- 22% (p =0.001) in LA group and in RFA group, respectively. Nodules with volume>30mL had significantly higher percentage volume reduction at 6 and 12months (-69 +/- 19 vs. -50 +/- 21, p=0.001) and (-73 +/- 18 vs. -54 +/- 23 8, p=0.001) in the LA group than in the RFA group, respectively. In both groups, operator's skills affected the results. Major complications occurred in 4 cases in each group (p=0.116)Conclusions: LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator's skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique.mixedPacella, Claudio Maurizio; Mauri, Giovanni; Cesareo, Roberto; Paqualini, Valerio; Cianni, Roberto; De Feo, Pierpaolo; Gambelunghe, Giovanni; Raggiunti, Bruno; Tina, Doris; Deandrea, Maurilio; Limone, Pier Paolo; Mormile, Alberto; Giusti, Massimo; Oddo, Silvia; Achille, Gaetano; Di Stasio, Enrico; Misischi, Irene; Papini, EnricoPacella, Claudio Maurizio; Mauri, Giovanni; Cesareo, Roberto; Paqualini, Valerio; Cianni, Roberto; De Feo, Pierpaolo; Gambelunghe, Giovanni; Raggiunti, Bruno; Tina, Doris; Deandrea, Maurilio; Limone, Pier Paolo; Mormile, Alberto; Giusti, Massimo; Oddo, Silvia; Achille, Gaetano; Di Stasio, Enrico; Misischi, Irene; Papini, Enric

Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up

Radiofrequency ablation for thyroid nodules: which indications? The first Italian opinion statement

Nodular thyroid disease is a very common finding in clinical practice, discovered by ultrasound (US) in about 50 % of the general population, with higher prevalence in women and in the elderly [1–4]. Whereas therapeutic flowchart is quite established and shared for malignant lesions, multiple options are now available for patients presenting with benign thyroid nod- ules, ranging from simple clinical and US follow-up to thyroid surgery. The majority of thyroid nodules, benign by fine-needle aspiration, are asymptomatic, stable, or slow- growing over time and require no treatmen