Ivan Ivanovski
University of Modena and Reggio Emilia
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Ivan Ivanovski.
Italian Journal of Pediatrics | 2014
Livia Garavelli; Lucia Santoro; Alexandra Iori; Giancarlo Gargano; Silvia Braibanti; Simona Pedori; Nives Melli; Daniele Frattini; Lucia Zampini; Tiziana Galeazzi; Lucia Padella; Stefano Pepe; Anita Wischmeijer; Simonetta Rosato; Ivan Ivanovski; Lorenzo Iughetti; Chiara Gelmini; Sergio Bernasconi; Andrea Superti-Furga; Andrea Ballabio; Orazio Gabrielli
Multiple Sulfatase Deficiency (MSD; OMIM 272200) is a rare autosomal recessive inborn error of metabolism caused by mutations in the sulfatase modifying factor 1 gene, encoding the formylglycine-generating enzyme (FGE), and resulting in tissue accumulation of sulfatides, sulphated glycosaminoglycans, sphingolipids and steroid sulfates. Less than 50 cases have been published so far. We report a new case of MSD presenting in the newborn period with hypotonia, apnoea, cyanosis and rolling eyes, hepato-splenomegaly and deafness. This patient was compound heterozygous for two so far undescribed SUMF1 mutations (c.191C > A; p.S64X and c.818A > G; p.D273G).
Genetics in Medicine | 2017
Livia Garavelli; Ivan Ivanovski; Stefano Giuseppe Caraffi; Daniela Santodirocco; Marzia Pollazzon; Duccio Maria Cordelli; Ebtesam M. Abdalla; P. Accorsi; Adam Mp; Chiara Baldo; Allan Bayat; E Belligni; Federico Bonvicini; Jeroen Breckpot; Bert Callewaert; Guido Cocchi; Goran Cuturilo; Koenraad Devriendt; Mary Beth P. Dinulos; Olivera Djuric; Roberta Epifanio; Francesca Faravelli; Debora Formisano; L. Giordano; Marina Grasso; Sabine Grønborg; Alessandro Iodice; Lorenzo Iughetti; Didier Lacombe; Massimo Maggi
Purpose:Mowat–Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined.Methods:Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype–phenotype correlations.Results:Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis.Conclusion:This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016
American Journal of Medical Genetics Part A | 2015
Livia Garavelli; Viviana Cordeddu; Stefania Errico; Patrizia Bertolini; Maria E. Street; Simonetta Rosato; Marzia Pollazzon; Anita Wischmeijer; Ivan Ivanovski; Paola Daniele; Ermanno Bacchini; Alfonsa Anna Lombardi; Giancarlo Izzi; Giacomo Biasucci; Carmine Del Rossi; Domenico Corradi; Giovanni Cazzaniga; Carlo Dominici; Cesare Rossi; Alessandro De Luca; Sergio Bernasconi; Riccardo Riccardi; Eric Legius; Marco Tartaglia
Noonan‐like syndrome with loose anagen hair (NSLH), also known as Mazzanti syndrome, is a RASopathy characterized by craniofacial features resembling Noonan syndrome, cardiac defects, cognitive deficits and behavioral issues, reduced growth generally associated with GH deficit, darkly pigmented skin, and an unique combination of ectodermal anomalies. Virtually all cases of NSLH are caused by an invariant and functionally unique mutation in SHOC2 (c.4A>G, p.Ser2Gly). Here, we report on a child with molecularly confirmed NSLH who developed a neuroblastoma, first suspected at the age 3 months by abdominal ultrasound examination. Based on this finding, scanning of the SHOC2 coding sequence encompassing the c.4A>G change was performed on selected pediatric cohorts of malignancies documented to occur in RASopathies (i.e., neuroblastoma, brain tumors, rhabdomyosarcoma, acute lymphoblastic, and myeloid leukemia), but failed to identify a functionally relevant cancer‐associated variant. While these results do not support a major role of somatic SHOC2 mutations in these pediatric cancers, this second instance of neuroblastoma in NSLAH suggests a possible predisposition to this malignancy in subjects heterozygous for the c.4A>G SHOC2 mutation.
American Journal of Medical Genetics Part A | 2016
Simonetta Rosato; Delfien Syx; Ivan Ivanovski; Marzia Pollazzon; Daniela Santodirocco; Loredana De Marco; Marina Beltrami; Bert Callewaert; Livia Garavelli; Fransiska Malfait
Biallelic defects in the RIN2 gene, encoding the Ras and Rab interactor 2 protein, are associated with a rare autosomal recessive connective tissue disorder, with only nine patients from four independent families reported to date. The condition was initially termed MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis), based on the clinical features of the first identified family; however, with the expansion of the clinical phenotype in additional families, it was subsequently coined RIN2 syndrome. Hallmark features of this condition include dysmorphic facial features with striking, progressive facial coarsening, sparse hair, normal to enlarged occipitofrontal circumference, soft redundant and/or hyperextensible skin, and scoliosis. Patients with RIN2 syndrome present phenotypic overlap with other conditions, including EDS (especially the dermatosparaxis and kyphoscoliosis subtypes). Here, we describe a 10th patient, the first patient of Caucasian origin and the oldest reported patient so far, who harbors the previously identified homozygous RIN2 mutation c.1878dupC (p. (Ile627Hisfs*7)). Besides the hallmark features, this patient also presents problems not previously associated with RIN2 syndrome, including cervical vertebral fusion, mild hearing loss, and colonic fibrosis. We provide an overview of the clinical findings in all reported patients with RIN2 mutations and summarize some of the possible pathogenic mechanisms that may underlie this condition.
World Journal of Gastroenterology | 2017
Ivan Ivanovski; Milos M. Jesic; Ana Ivanovski; Livia Garavelli; Petar Ivanovski
The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Conclusion: Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liver damage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.
Psychology and Neuroscience | 2018
Andrea Zangrandi; Federico Gasparini; Alessandro Marti; Ivan Ivanovski; Manuela Napoli; Caterina Barletta-Rodolfi; Damiano Angelini; Enrico Ghidoni
Idiopathic basal ganglia calcification, also known as Fahr’s disease, is a rare neurological disorder characterized by abnormal calcium deposition in basal ganglia and cerebellum, usually associated with neuropsychiatric symptoms and movement disorders. The same diagnostic label probably encompasses different diseases with variable characteristics. Here we report 4 patients who meet criteria for Fahr’s disease, presenting different radiological, neuropsychological, psychiatric, and systemic features, to assess the role of cerebral calcifications in the clinical picture. All patients underwent complete neuropsychological evaluations at our unit. Cerebral computed tomography scans were obtained for all patients, and magnetic resonance images were also available for patients 1, 2, and 4. Patients presented heterogeneous radiological and neuropsychological features; overall clinical pictures varied from completely asymptomatic to severe cognitive impairment. In our patients, the site and extent of brain calcification appear only partially indicative of clinical severity because the worsening of brain calcifications does not lead to a corresponding clinical worsening.
Genetics in Medicine | 2018
Ivan Ivanovski; Olivera Djuric; Stefano Giuseppe Caraffi; Daniela Santodirocco; Marzia Pollazzon; Simonetta Rosato; Duccio Maria Cordelli; Ebtesam M. Abdalla; P. Accorsi; Adam Mp; Paola Francesca Ajmone; Magdalena Badura-Stronka; Chiara Baldo; Maddalena Baldi; Allan Bayat; Stefania Bigoni; Federico Bonvicini; Jeroen Breckpot; Bert Callewaert; Guido Cocchi; Goran Cuturilo; Daniele De Brasi; Koenraad Devriendt; Mary Beth P. Dinulos; Tina Duelund Hjortshøj; Roberta Epifanio; Francesca Faravelli; Agata Fiumara; Debora Formisano; L. Giordano
PurposeMowat–Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype–phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.ResultsAll anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.
American Journal of Medical Genetics Part A | 2018
Margherita Lucia De Bernardi; Ivan Ivanovski; Stefano Giuseppe Caraffi; Ilenia Maini; Maria Elisabeth Street; Allan Bayat; Marcella Zollino; Francesca Lepri; Maria Gnazzo; Edoardo Errichiello; Andrea Superti-Furga; Livia Garavelli
KBG syndrome is characterized by short stature, distinctive facial features, and developmental/cognitive delay and is caused by mutations in ANKRD11, one of the ankyrin repeat‐containing cofactors. After the advent of whole exome sequencing, the number of clinical reports with KBG diagnosis has increased, leading to a revision of the phenotypic spectrum associated with this syndrome. Here, we report a female child showing clinical features of the KBG syndrome in addition to a caudal appendage at the coccyx with prominent skin fold and a peculiar calcaneus malformation. Exons and exon–intron junctions targeted resequencing of SH3PXD2B and MASP1 genes, known to be associated with prominent coccyx, gave negative outcome, whereas sequencing of ANKRD11 whose mutations matched the KBG phenotype of the proband showed a de novo heterozygous frameshift variant c.4528_4529delCC in exon 9 of ANKRD11. This report contributes to expand the knowledge of the clinical features of KBG syndrome and highlights the need to search for vertebral anomalies and suspect this condition in the presence of a prominent, elongated coccyx.
American Journal of Medical Genetics Part A | 2018
Ivan Ivanovski; Susan Akbaroghli; Marzia Pollazzon; Chiara Gelmini; Stefano Giuseppe Caraffi; Mahboubeh Mansouri; Zahra Chavoshzadeh; Simonetta Rosato; Valeria Polizzi; Giancarlo Gargano; Marielle Alders; Livia Garavelli; Raoul C. M. Hennekam
Biallelic variants in FAT4 are associated with the two disorders, Van Maldergem syndrome (VMS) (n = 11) and Hennekam syndrome (HS) (n= 40). Both conditions are characterized by a typical facial gestalt and mild to moderate intellectual disability, but differ in the occurrence of neonatal hypotonia and feeding problems, hearing loss, tracheal anomalies, and osteopenia in VMS, and lymphedema in HS. VMS can be caused by autosomal recessive variants in DCHS1 as well, and HS can also be caused by autosomal recessive variants in CCBE1 and ADAMTS3. Here we report two siblings with VMS and one girl with HS, all with FAT4 variants, and provide an overview of the clinical findings in all patients reported with FAT4 variants. Our comparison of the complete phenotypes of patients with VMS and HS indicates a resemblance of several signs, but differences in several other main signs and symptoms, each of marked importance for affected individuals.
Molecular Syndromology | 2016
Ilenia Maini; Ivan Ivanovski; Alessandro Iodice; Simonetta Rosato; Marzia Pollazzon; Manuela Mussini; E Belligni; Charles Coutton; Maria Marinelli; Veronica Barbieri; Manuela Napoli; Rosario Pascarella; Chiara Sartori; Francesca Madia; Carlo Fusco; Fabrizia Franchi; Maria E. Street; Livia Garavelli
To date, 5 cases of 17p13.1 microduplications have been described in the literature. Intellectual disability was reported as the core feature, together with minor facial dysmorphisms and obesity, but a characteristic phenotype for 17p13.1 microduplication has not been delineated. Here, we describe a patient with a 1.56-Mb de novo duplication in 17p13.1, affected by mild intellectual disability, facial dysmorphisms, obesity, and diabetes. By comparing the different phenotypes of currently described cases, we delineated the main clinical features of 17p13.1 microduplication syndrome. All patients described to date had variable facial dysmorphisms; therefore, it was difficult to define a common facial gestalt. Furthermore, we stress endocrinological abnormalities as important features and the need to monitor these over time.