Papers by Antonino Romanzo
Diagnostics
Von Hippel–Lindau (VHL) disease is a heritable cancer syndrome in which benign and malignant tumo... more Von Hippel–Lindau (VHL) disease is a heritable cancer syndrome in which benign and malignant tumors and/or cysts develop throughout the central nervous system (CNS) and visceral organs. The disease results from mutations in the VHL tumor suppressor gene located on chromosome 3 (3p25-26). A majority of individuals (60–80%) with VHL disease will develop CNS hemangioblastomas (HMG). Endolymphatic sac tumor (ELST) is an uncommon, locally aggressive tumor located in the medial and posterior petrosal bone region. Its diagnosis is based on clinical, radiological, and pathological correlation, and it can occur in the setting of VHL in up to 10–15% of individuals. We describe a 17-year-old male who presented with a chief complaint of hearing loss. Brain and spine Magnetic Resonance Imaging documented the presence of an expansive lesion in the left cerebellar hemisphere, compatible with HMG in association with a second cerebellopontine lesion compatible with ELST. The peculiarity of the repor...
Investigative Ophthalmology & Visual Science, 2012
Applied Immunohistochemistry & Molecular Morphology, 2021
Retinoblastoma(RB) patients have a high risk to develop second malignant neoplasm (SMN). Dienceph... more Retinoblastoma(RB) patients have a high risk to develop second malignant neoplasm (SMN). Diencephalic tumors(DT) are rare in paediatric age. A retrospective review was performed over 21 years period. Out of 169 RB patients, 3 presented a DT. Two patients presented a Rb1 germline mutation and none received radiotherapy. DT in previously treated RB patients seems a peculiar SMN. However, considering the site, the short time interval from RB and the absence of radiotherapy, an alternative pathogenic mechanism could be supposed. The same embryological origin of the retina and the diencephalon should be considered and biological studies are needed.
Cancers, 2020
Retinoblastoma (RB) is the most common tumor of the eye in early childhood. Although recent advan... more Retinoblastoma (RB) is the most common tumor of the eye in early childhood. Although recent advances in conservative treatment have greatly improved the visual outcome, local tumor control remains difficult in the presence of massive vitreous seeding. Traditional biopsy has long been considered unsafe in RB, due to the risk of extraocular spread. Thus, the identification of new biomarkers is crucial to design safer diagnostic and more effective therapeutic approaches. Exosomes, membrane-derived nanovesicles that are secreted abundantly by aggressive tumor cells and that can be isolated from several biological fluids, represent an interesting alternative for the detection of tumor-associated biomarkers. In this study, we defined the protein signature of exosomes released by RB tumors (RBT) and vitreous seeding (RBVS) primary cell lines by high resolution mass spectrometry. A total of 5666 proteins were identified. Among these, 5223 and 3637 were expressed in exosomes RBT and one RBVS...
Italian Journal of Pediatrics, 2019
Background: Childhood obesity has been correlated with coronary heart disease, but the correlatio... more Background: Childhood obesity has been correlated with coronary heart disease, but the correlation with microvascular disease remains unclear. The retinal microcirculation is affected early in the process of atherosclerosis and it offers the opportunity to indirectly study the effects of obesity on small brain vessels. Insulin-like growth factor 1 (IGF-I) is involved in angiogenesis and it has a crucial role in retinal vascularization. Methods: A single-centre cross-sectional study was performed in 268 children and adolescents (116 males; mean age 13.03 ± 1.9 years,) with overweight/obesity, in order to identify risk factors for early retinopathy. Results: Nine patients (3.3%) showed signs of retinopathy, defined as arteriovenous crossings and/or papilledema. Body mass index and fat mass, analysed by Dual X-ray Absorptiometry, were not different in patients with or without retinopathy. Patients with retinopathy were pubertal and showed higher waist circumference (107.78 ± 15.83 versus 99.46 ± 10.85 cm; p: 0.027), waist circumference/height ratio (0.66 ± 0.07 versus 0.62 ± 0.05; p: 0.04) and IGF-I SDS (0.03 ± 1.3 versus − 0.66 ± 0.9; p: 0.04). Multivariate analysis (after correction for sex, age, family history of type 2 diabetes mellitus, obesity, cardiovascular disease, hypertension and dyslipidaemia) showed that waist circumference/height ratio and IGF-I SDS were the only variables independently correlated with the presence of retinopathy. Conclusions: Retinal vascular changes may become evident as an early complication of overweight and obesity, even during childhood and adolescence. Relatively high levels of IGF-I during this phase may act as an additional risk factor for microvascular damage. The screening for retinopathy should be proposed to all children and adolescents with overweight/obesity.
Canadian Journal of Ophthalmology / Journal Canadien d'Ophtalmologie, 2016
symptom, followed by ipsilateral nasal obstruction (73%) and aural dysfunction (62%). 2 Cranial n... more symptom, followed by ipsilateral nasal obstruction (73%) and aural dysfunction (62%). 2 Cranial nerve palsies were found in 20% of patients with NPC. 2 When a cranial nerve palsy is present, the trigeminal nerve (12.5%) or abducens nerve (10.5%) are typically involved, although involvement of each cranial nerve has been reported. 2 Optic nerve involvement, with subsequent decreased VA, is a very rare presentation of NPC. There have been only 6 reports of decreased VA as the initial presenting feature of NPC, in either the primary or recurrent setting, in which only 2 of these cases presented with no light perception vision loss. 3-8 In contrast to the previously published case reports, this patient was from Hungary, an area not generally recognized as having a high incidence of NPC. This case further highlights that ophthalmic signs and symptoms may occasionally be the initial manifestation of NPC.
Annali dell'Istituto superiore di sanità, 2015
Visual performance of eyes with congenital pathologies is conditioned by an early diagnosis. Fami... more Visual performance of eyes with congenital pathologies is conditioned by an early diagnosis. Families having problems in accessing health services risk to delay or miss both an early diagnosis and an early treatment and amblyopia (lazy eye) prevention. In our hospital, all full-term, healthy newborns are thoroughly examined by an ophthalmologist in the maternal ward, 1 to 3 days after birth. Among the first 5000 newborns examined, a high incidence of congenital pathologies compared to international literature was reported, with differences between Caucasians and non-Caucasians. Performing an early in-hospital thorough eye examination in all newborns as a screening would be an effective way to miss none and to start an early and effective pathway of disease treatment.
BMC Cancer, 2015
Background: Retinoblastoma (RB) is the most common malignant childhood tumor of the eye and resul... more Background: Retinoblastoma (RB) is the most common malignant childhood tumor of the eye and results from inactivation of both alleles of the RB1 gene. Nowadays RB genetic diagnosis requires classical chromosome investigations, Multiplex Ligation-dependent Probe Amplification analysis (MLPA) and Sanger sequencing. Nevertheless, these techniques show some limitations. We report our experience on a cohort of RB patients using a combined approach of Next-Generation Sequencing (NGS) and RB1 custom array-Comparative Genomic Hybridization (aCGH). Methods: A total of 65 patients with retinoblastoma were studied: 29 cases of bilateral RB and 36 cases of unilateral RB. All patients were previously tested with conventional cytogenetics and MLPA techniques. Fifty-three samples were then analysed using NGS. Eleven cases were analysed by RB1 custom aCGH. One last case was studied only by classic cytogenetics. Finally, it has been tested, in a lab sensitivity assay, the capability of NGS to detect artificial mosaicism series in previously recognized samples prepared at 3 different mosaicism frequencies: 10, 5, 1 %. Results: Of the 29 cases of bilateral RB, 28 resulted positive (96.5 %) to the genetic investigation: 22 point mutations and 6 genomic rearrangements (four intragenic and two macrodeletion). A novel germline intragenic duplication, from exon18 to exon 23, was identified in a proband with bilateral RB. Of the 36 available cases of unilateral RB, 8 patients resulted positive (22 %) to the genetic investigation: 3 patients showed point mutations while 5 carried large deletion. Finally, we successfully validated, in a lab sensitivity assay, the capability of NGS to accurately measure level of artificial mosaicism down to 1 %. Conclusions: NGS and RB1-custom aCGH have demonstrated to be an effective combined approach in order to optimize the overall diagnostic procedures of RB. Custom aCGH is able to accurately detect genomic rearrangements allowing the characterization of their extension. NGS is extremely accurate in detecting single nucleotide variants, relatively simple to perform, cost savings and efficient and has confirmed a high sensitivity and accuracy in identifying low levels of artificial mosaicisms.
Anticancer research, 2014
Trilateral retinoblastoma (TRB) is a rare disease associating bilateral retinoblastoma (RB) with ... more Trilateral retinoblastoma (TRB) is a rare disease associating bilateral retinoblastoma (RB) with primitive intracranial neuroblastic tumor. To verify the occurrence of TRB in a single-Center case series and point out the clinical relevance of a baseline brain magnetic resonance imaging (MRI) in RB, focusing on pineal gland lesions. Baseline MRI was routinely performed in all cases of RB from 1999. All MRIs were reviewed for this study and the RB database was checked in order to identify patients characteristics, treatments and follow-up. A total of 107 patients with RB were diagnosed between 1999 and 2012. Sixty-two patients had unilateral RB and 45 bilateral RB. MRI revealed the presence of pineal gland lesions in 10 patients (9%); seven were considered pineal benign cysts (6.5%), while in three patients (2.8%), TRB was suspected. All patients with TRB presented hereditary RB. In one patient, the suspected TRB was metachronous and in the other two patients was synchronous. Biopsy w...
British Journal of Ophthalmology, 2009
Background: Metastatic spread in retinoblastoma is a rare occurrence in developed countries but s... more Background: Metastatic spread in retinoblastoma is a rare occurrence in developed countries but still associated with a poor prognosis. Patients and Methods: Medical records of all metastatic retinoblastoma diagnosed during a 20year period were retrospectively reviewed. Results: 6 patients out of 104 presented a metastatic disease with an incidence at diagnosis of 2%. Three had a metastatic disease at diagnosis, one patient a trilateral retinoblastoma and 2 a metastatic spread after enucleation. All but one were sporadic retinoblastoma. Central Nervous System (CNS) involvement was reported in 5 patients while one patient had an intra-orbital lesion and bone and bone marrow spread. Different treatment strategies were administered based on local treatment plus chemotherapy and radiotherapy with or without high dose chemotherapy. Ifosfamide/carboplatin/etoposide (ICE) regimen was administered in 3 patients resulting in a partial response. Out of 6 patients, 4 died and 2 patients are alive at 60 and 63 months from diagnosis. Both children with a long follow-up were treated with high dose chemotherapy. All but one patients with CNS involvement died; the survivor was a patient with pineal involvement.. Conclusion: This retrospective review confirms a curable strategy based on local treatment and conventional plus high dose chemotherapy. Patients with CNS involvement remain incurable.
Pediatric Blood & Cancer, 2015
Certainly, considering the incidence of a pylocitic astrocytoma (1 per 50,000) and retinoblastoma... more Certainly, considering the incidence of a pylocitic astrocytoma (1 per 50,000) and retinoblastoma (1 per 15,000), the occurrence of both these two tumors is a rare coincidence. Further analyses on large series are needed to clarify the risk and pathogenesis of CNS tumors in RB patients according to RB1 alteration and treatments.
Journal of Cardiovascular Development and Disease, 2022
Cardiomyopathy (CMP) is a rare disease in the pediatric population, with a high risk of morbidity... more Cardiomyopathy (CMP) is a rare disease in the pediatric population, with a high risk of morbidity and mortality. The genetic etiology of CMPs in children is extremely heterogenous. These two factors play a major role in the difficulties of establishing standard diagnostic and therapeutic protocols. Isolated CMP in children is a frequent finding, mainly caused by sarcomeric gene variants with a detection rate that can reach up to 50% of analyzed cohorts. Complex multisystemic forms of pediatric CMP are even more heterogenous. Few studies in literature take into consideration this topic as the main core since it represents a rarity (systemic CMP) within a rarity (pediatric population CMP). Identifying etiology in this cohort is essential for understanding prognosis, risk stratification, eligibility to heart transplantation and/or mechanical-assisted procedures, preventing multiorgan complications, and relatives’ recurrence risk calculation. The previous points represent a cornerstone ...
Pediatric Allergy and Immunology
Vernal keratoconjunctivitis (VKC) is a bilateral, chronic, allergic condition mostly affecting ch... more Vernal keratoconjunctivitis (VKC) is a bilateral, chronic, allergic condition mostly affecting children. Clinical evaluations may not necessarily reflect the impact of the disease on the patients’ health‐related quality of life (HRQoL). We aimed to evaluate HRQoL in children at VKC diagnosis and to analyze correlations between HRQoL and clinical and laboratory variables.
BMC Cancer, 2015
Retinoblastoma (RB) is the most common malignant childhood tumor of the eye and results from inac... more Retinoblastoma (RB) is the most common malignant childhood tumor of the eye and results from inactivation of both alleles of the RB1 gene. Nowadays RB genetic diagnosis requires classical chromosome investigations, Multiplex Ligation-dependent Probe Amplification analysis (MLPA) and Sanger sequencing. Nevertheless, these techniques show some limitations. We report our experience on a cohort of RB patients using a combined approach of Next-Generation Sequencing (NGS) and RB1 custom array-Comparative Genomic Hybridization (aCGH). A total of 65 patients with retinoblastoma were studied: 29 cases of bilateral RB and 36 cases of unilateral RB. All patients were previously tested with conventional cytogenetics and MLPA techniques. Fifty-three samples were then analysed using NGS. Eleven cases were analysed by RB1 custom aCGH. One last case was studied only by classic cytogenetics. Finally, it has been tested, in a lab sensitivity assay, the capability of NGS to detect artificial mosaicism series in previously recognized samples prepared at 3 different mosaicism frequencies: 10, 5, 1 %. Of the 29 cases of bilateral RB, 28 resulted positive (96.5 %) to the genetic investigation: 22 point mutations and 6 genomic rearrangements (four intragenic and two macrodeletion). A novel germline intragenic duplication, from exon18 to exon 23, was identified in a proband with bilateral RB. Of the 36 available cases of unilateral RB, 8 patients resulted positive (22 %) to the genetic investigation: 3 patients showed point mutations while 5 carried large deletion. Finally, we successfully validated, in a lab sensitivity assay, the capability of NGS to accurately measure level of artificial mosaicism down to 1 %. NGS and RB1-custom aCGH have demonstrated to be an effective combined approach in order to optimize the overall diagnostic procedures of RB. Custom aCGH is able to accurately detect genomic rearrangements allowing the characterization of their extension. NGS is extremely accurate in detecting single nucleotide variants, relatively simple to perform, cost savings and efficient and has confirmed a high sensitivity and accuracy in identifying low levels of artificial mosaicisms.
Pediatric Blood & Cancer, 2015
BMC ophthalmology, 2014
Congenital cystic eye is an exceedingly rare ocular malformative disease, originated from the fai... more Congenital cystic eye is an exceedingly rare ocular malformative disease, originated from the failure in the invagination of the optic vesicle during the fetal period and it can be associated with other ocular and non-ocular abnormalities. Diagnosis is based on clinical, radiological and histological features. We report a case of a congenital cystic eye associated with a cerebellar lesion accidentally detected at magnetic resonance imaging. Biopsy of the mass has not been performed due to parental rejection. Based on radiologic features and absence of clinical signs, a low-grade glioma diagnosis was hypothesized, but histological characterization was not obtained. Follow-up neuro-imaging 6 months after diagnosis showed that intracranial lesion spontaneously regressed without any treatment. Our report stresses the importance of early MRI in children with ocular malformations, in order to detect associated intracranial defects, also of non-malformative origin. Additionally, we debate ...
Cancer Genetics, 2013
Retinoblastoma (RB) is the most common eye tumor in children; it originates from germline and/ or... more Retinoblastoma (RB) is the most common eye tumor in children; it originates from germline and/ or somatic mutations that inactivate both alleles of the RB1 gene located on chromosome 13q14. Patients with unilateral or bilateral RB infrequently may develop an additional intracranial neuroblastic tumor, usually in the pineal gland, which characterizes the trilateral retinoblastoma (TRB) syndrome. The most common chromosomal abnormalities detected in TRB are deletions at 13q14, even if some rare cases of RB1 point mutations were described. In our report, we investigated two patients with TRB who showed a germline RB1 point mutation that has never been found to date and a large deletion involving RB1, respectively. Genetic data were compared to our in-house series and to current literature; these data suggested a role for other candidate regions in the pathogenesis of TRB. Moreover, our study highlights the need for new approaches allowing a multigenic analysis to clarify the genotypeÀphenotype correlation in TRB.
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Papers by Antonino Romanzo