Celeste Panteghini
Carlo Besta Neurological Institute
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Featured researches published by Celeste Panteghini.
Seminars in Pediatric Neurology | 2012
Celeste Panteghini; Giovanna Zorzi; Paola Venco; Sabrina Dusi; Chiara Reale; Dario Brunetti; Luisa Chiapparini; Federica Zibordi; Brigitte Siegel; Barbara Garavaglia; Alessandro Simonati; Enrico Bertini; Nardo Nardocci; Valeria Tiranti
Neurodegeneration with brain iron accumulation (NBIA) defines a wide spectrum of clinical entities characterized by iron accumulation in specific regions of the brain, predominantly in the basal ganglia. We evaluated the presence of FA2H and C19orf12 mutations in a cohort of 46 Italian patients with early onset NBIA, which were negative for mutations in the PANK2 and PLA2G6 genes. Follow-up molecular genetic and in vitro analyses were then performed. We did not find any mutations in the FA2H gene, although we identified 3 patients carrying novel mutations in the C19orf12 gene. The recent discovery of new genes responsible for NBIA extends the spectrum of the genetic investigation now available for these disorders and makes it possible to delineate a clearer clinical-genetic classification of different forms of this syndrome. A large fraction of patients still remain without a molecular genetics diagnosis, suggesting that additional NBIA genes are still to be discovered.
Parkinsonism & Related Disorders | 2017
Miryam Carecchio; Niccolo E. Mencacci; Alessandro Iodice; Roser Pons; Celeste Panteghini; Giovanna Zorzi; Federica Zibordi; Anastasios Bonakis; Argyris Dinopoulos; Joseph Jankovic; Leonidas Stefanis; Kailash P. Bhatia; Valentina Monti; Lea R'Bibo; Liana Veneziano; Barbara Garavaglia; Carlo Fusco; Nicholas W. Wood; Maria Stamelou; Nardo Nardocci
Introduction ADCY5 mutations have been recently identified as an important cause of early-onset hyperkinetic movement disorders. The phenotypic spectrum associated with mutations in this gene is expanding. However, the ADCY5 mutational frequency in cohorts of paediatric patients with hyperkinetic movement disorders has not been evaluated. Methods We performed a screening of the entire ADCY5 coding sequence in 44 unrelated subjects with genetically undiagnosed childhood-onset hyperkinetic movement disorders, featuring chorea alone or in combination with myoclonus and dystonia. All patients had normal CSF analysis and brain imaging and were regularly followed-up in tertiary centers for paediatric movement disorders. Results We identified five unrelated subjects with ADCY5 mutations (11% of the cohort). Three carried the p. R418W mutation, one the p. R418Q and one the p. R418G mutation. Mutations arose de novo in four cases, while one patient inherited the mutation from his similarly affected father. All patients had delayed motor and/or language milestones with or without axial hypotonia and showed generalized chorea and dystonia, with prominent myoclonic jerks in one case. Episodic exacerbations of the baseline movement disorder were observed in most cases, being the first disease manifestation in two patients. The disease course was variable, from stability to spontaneous improvement during adolescence. Conclusion Mutations in ADCY5 are responsible for a hyperkinetic movement disorder that can be preceded by episodic attacks before the movement disorder becomes persistent and is frequently misdiagnosed as dyskinetic cerebral palsy. A residual degree of neck hypotonia and a myopathy-like facial appearance are frequently observed in patients with ADCY5 mutations.
European Journal of Paediatric Neurology | 2016
Davide Tonduti; Simona Orcesi; Emma M. Jenkinson; Imen Dorboz; Florence Renaldo; Celeste Panteghini; Gillian I. Rice; Marco Henneke; John H. Livingston; Monique Elmaleh; Lydie Burglen; M.A.A.P. Willemsen; Luisa Chiapparini; Barbara Garavaglia; Diana Rodriguez; Odile Boespflug-Tanguy; Isabella Moroni; Yanick J. Crow
BACKGROUND Cystic leukoencephalopathy without megalencephaly is a disorder related in some cases to RNASET2 mutations and characterized by bilateral anterior temporal subcortical cysts and multifocal lobar white matter lesions with sparing of central white matter structures. This phenotype significantly overlaps with the sequelae of in utero cytomegalovirus (CMV) infection, including the presence of intracranial calcification in some cases. Aicardi-Goutières syndrome (AGS) is another inherited leukodystrophy with cerebral calcification mimicking congenital infection. Clinical, radiological and biochemical criteria for the diagnosis of AGS have been established, although the breadth of phenotype associated with mutations in the AGS-related genes is much greater than previously envisaged. PATIENTS AND METHODS We describe the clinical, biochemical and radiological findings of five patients demonstrating a phenotype reminiscent of AGS. RESULTS All patients were found to carry biallelic mutations of RNASET2. CONCLUSIONS Our patients illustrate the clinical and radiological overlap that can be seen between RNASET2-related leukodystrophy and AGS in some cases. Our data highlight the need to include both disorders in the same differential diagnosis, and hint at possible shared pathomechanisms related to auto-inflammation which are worthy of further investigation.
Current Neurology and Neuroscience Reports | 2016
Davide Tonduti; Luisa Chiapparini; Isabella Moroni; Anna Ardissone; Giovanna Zorzi; Federica Zibordi; Sergio Raspante; Celeste Panteghini; Barbara Garavaglia; Nardo Nardocci
Neostriatal abnormalities can be observed in a very large number of neurological conditions clinically dominated by the presence of movement disorders. The neuroradiological picture in some cases has been described as “bilateral striatal necrosis” (BSN). BSN represents a condition histo-pathologically defined by the involvement of the neostriata and characterized by initial swelling of putamina and caudates followed by degeneration and cellular necrosis. After the first description in 1975, numerous acquired and hereditary conditions have been associated with the presence of BSN. At the same time, a large number of disorders involving neostriata have been described as BSN, in some cases irrespective of the presence of signs of cavitation on MRI. As a consequence, the etiological spectrum and the nosographic boundaries of the syndrome have progressively become less clear. In this study, we review the clinical and radiological features of the conditions associated with MRI evidence of bilateral striatal lesions. Based on MRI findings, we have distinguished two groups of disorders: BSN and other neostriatal lesions (SL). This distinction is extremely helpful in narrowing the differential diagnosis to a small group of known conditions. The clinical picture and complementary exams will finally lead to the diagnosis. We provide an update on the etiological spectrum of BSN and propose a diagnostic flowchart for clinicians.
Parkinsonism & Related Disorders | 2016
Francesco Nicita; Lorena Travaglini; Sandro Sabatini; Barbara Garavaglia; Celeste Panteghini; Massimiliano Valeriani; Enrico Bertini; Nardo Nardocci; Federico Vigevano; Alessandro Capuano
ATP1A3 gene mutations are associated with alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism (RPD) and CAPOS syndrome (Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, and Sensorineural deafness) [1]. So far, nearly 60 distinct ATP1A3 mutations have been described in association with a wide spectrum of neurological and psychiatric symptoms. These may go beyond the well-defined boundaries of RDP or AHC, thus generating overlapping phenotypes [2,3]. In this study, we describe two sporadic patients harboring novel ATP1A3 mutations and showing overlapping or atypical clinical features in the spectrum of RDP and AHC. Patient 1 is a 17-year-old girl who showed right focal clonic seizures at the age of 3 months. At that time, brain MRI was normal and electroencephalogram (EEG) showed epileptic discharges in left temporal lobe. In addition, she had paroxysmal episodes, lasting many hours, and characterized by generalized weakness, tonic gaze deviation, neck hyperextension, or hypotonia in the right hemisoma. A treatment based on phenobarbital combined with and carbamazepine proved effective. Over the following years a slight delay in motor and cognitive skills became evident. At the age of 12 years and 10 months, she abruptly developed within few hours a clinical picture characterized by ideomotor slowdown, apathy, facial hypomimiawith sialorrhoea, slurred speech, bradykinesia, rigidity and dystonic postures mainly of the right hand. The above symptoms worsened in 24 hours and remained stable in the next days (video 1). EEGwas unremarkable. Full metabolic tests in blood and cerebro-spinal fluid (CSF), were normal. RDP was hypothesized and ATP1A3 gene sequencing was performed. A novel heterozygous missense variant c.1747G>T; p.D583Y was identified. This variant was not found in both parents and in 100 unrelated healthy controls. In silico analysis by SIFT (sift.jcvi.org/) and PolyPhen-2 (http://genetics.bwh.harvard.edu/pph2/prediction) classified the mutation as damaging. L-Dopa was ineffective, while lorazepam 1mg/daywas effective in reducing drooling, anxiety and
Journal of Child Neurology | 2015
Carlo Fusco; Daniele Frattini; Celeste Panteghini; Rosario Pascarella; Barbara Garavaglia
Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder, with onset in the first or second year of life. Mutations in the PLA2G6 gene encoding iPLA2-VI, a calcium-independent phospholipase, have been identified in these children. In classic infantile neuroaxonal dystrophy–affected children, psychomotor regression is the most frequent presentation, usually with ataxia and optic atrophy, followed by the development of tetraparesis. We report a child carrying a homozygous mutation in the PLA2G6 gene with neonatal onset of disease and somewhat different clinical phenotype such as severe congenital hypotonia, marked weakness, and bulbar signs suggesting that infantile neuroaxonal dystrophy can start at birth with atypical phenotype.
Parkinsonism & Related Disorders | 2016
Miryam Carecchio; Celeste Panteghini; Chiara Reale; Chiara Barzaghi; Valentina Monti; Luigi Romito; Francesco Sasanelli; Barbara Garavaglia
INTRODUCTION Mutations in GNAL have been associated with adult-onset cranio-cervical dystonia, but a limited number of cases have been reported so far and the clinical spectrum associated with this gene still needs to be fully characterized. METHODS We identified an Italian family with adult-onset, dominantly-inherited dystonia whose members presented with different combinations of dystonia affecting the cervical, oro-mandibular and laryngeal regions associated with prominent tremor in some cases. Pure asymmetric upper limb dystonic tremor was present in one of the members and jerky cervical dystonia was also observed. A dedicate dystonia gene panel (Illumina) was used to screen for dystonia-associated genes and Sanger sequencing was performed to confirm results obtained and to perform segregation analysis. RESULTS A novel single-base mutation in GNAL exon 9 (c.628G>A; p.Asp210Asn) leading to an aminoacidic substitution was identified and confirmed by Sanger sequencing. In silico prediction programmes as well as segregation analysis confirmed its pathogenicity. Clinically, no generalization of dystonia was observed after onset and DBS lead to an excellent motor outcome in two cases. CONCLUSION We report a novel GNAL mutation and expand the clinical spectrum associated with mutations in this gene to comprise pure asymmetric dystonic tremor and a jerky cervical phenotype partially mimicking DYT11 positive cases.
Movement Disorders | 2017
Silvia Esposito; Miryam Carecchio; Davide Tonduti; Veronica Saletti; Celeste Panteghini; Luisa Chiapparini; Giovanna Zorzi; Chiara Pantaleoni; Barbara Garavaglia; Dimitri Krainc; Steven Lubbe; Nardo Nardocci; Niccolo E. Mencacci
Recently, de novo and bi-allelic mutations in PDE10A, encoding a cyclic nucleotide phosphodiesterase selectively expressed in striatal medium spiny neurons, have been recognized as a cause of childhood-onset chorea. Brain MRI consistently showed striking bilateral striatal lesions in the 3 patients with de novo mutations identified to date. Interestingly, these radiological features were not observed in any of the patients with recessive mutations despite a more severe clinical presentation. Herein, we describe a patient carrying a de novo PDE10A mutation presenting with bilateral striatal MRI abnormalities and a yet unreported circadian pattern of nonprogressive chorea. The patient is an Italian 5-year-old boy born full term after an uneventful pregnancy and delivery. Motor and language milestones were normally achieved. At age 2.5 he presented with subacute onset of chorea involving the lower limbs causing frequent falls. No febrile illness preceded the onset of movement disorder. During the following 3 months, chorea slowly progressed and became generalized with sparing of the oro-mandibular and facial muscles and he developed mild dystonic posturing of upper limbs. At this stage, diurnal fluctuations of chorea became evident, with increased severity lasting about 2 hours after waking up in the morning (Video 1). Chorea slowly improved during the day, showed no worsening before falling asleep, and was absent at night. Cognitive assessment was normal (total IQ 5 114). Brain MRI performed 2 months after onset of symptoms revealed bilateral symmetrical hyper-intense lesions on T2weighted, FLAIR and diffusion weighted images involving the putamen and caudate nuclei (Fig. 1). An extensive diagnostic workup, including CSF analysis (neurotransmitters, folates), plasma lactate/pyruvate, activity of the respiratory chain enzymes in muscle, basic metabolic panel, and a screening for autoimmune and infectious conditions, was unremarkable. Targeted sequencing of striatal necrosis-related genes yielded negative results. Whole-exome sequencing was performed as previously described and revealed a heterozygous known pathogenic PDE10A missense variant (c.1000T>C, p.Phe334Leu; transcript ENST00000539869). Sanger sequencing confirmed the presence of the variant and segregation analysis in the parents demonstrated it arose de novo in the proband. The patient was started on trihexyphenidyl (1 mg daily), which was discontinued because of behavioral changes. Tetrabenazine was not administered because of the patient’s young age and overall mild severity of chorea. After 2 years of follow-up, chorea showed no progression, but diurnal fluctuations consistently persisted (Video 1) and brain MRI was unchanged. No additional therapies were started. This report confirms the homogeneous phenotype related to dominant PDE10A mutations. The unique clinical presentation of childhood-onset chorea with a scarcely progressive course associated with bilateral striatal lesions is highly suggestive of dominant PDE10A mutations. To date, only 2 recurrent dominant pathogenic variants have been identified (p.Phe300Leu and p.Phe334Leu, each detected in 2 unrelated patients), suggesting that these residues are mutational hotspots. Unlike previously reported PDE10A mutation carriers, our case showed marked diurnal fluctuations with chorea being more severe upon awakening in the morning. Differently from our case, patients with ADCY5-related chorea often show characteristic exacerbations lasting up to hours both upon awakening and falling asleep. Cases with DOPA-responsive dystonia as a result of GCH1 mutations present with marked worsening of symptoms during the day. The pattern of motor fluctuation observed in this case of PDE10A-related chorea may represent an additional clue for the identification of this rare movement disorder.
Journal of Neurology | 2017
Alessandro Iodice; Celeste Panteghini; Carlotta Spagnoli; Grazia Gabriella Salerno; Daniele Frattini; Carmela Russo; Barbara Garavaglia; Carlo Fusco
We read with great interest the paper by Leonardi et al. [1] which presented an Italian family harboring a novel homozygous mutation in SPG56/CYP2U1 with pigmentary degenerative maculopathy as a prominent feature. SPG56, due to CYP2U1 mutation, is a rare autosomal recessive early-onset complicated form of hereditary spastic paraplegia with spasticity in the upper limbs, rare dystonic postures, cognitive impairment and subclinical neuropathy [2]. The phenotypic spectrum of SPG56 has been recently expanded: 18 subjects have currently been reported with increasing clinical and neuroradiological heterogeneity [1–6]. We would like to present a further case with two novel mutations in in CYP2U1 gene and pigmentary degenerative maculopathy to highlight how the phenotypic variability so far reported might also be age-dependent and not only related to genetic heterogeneity. This 34-year-old patient was the first daughter of healthy non-consanguineous Caucasian parents. During the long-term follow-up started since the first year of age, she underwent different genetic and neurometabolic investigations. We finally identified thanks to targeted re-sequencing TruSeq Custom Amplicon panel (MiSeq Illumina platform) formed by 21 idiopathic intracranial calcification genes two novel heterozygote mutations in SPG56/CYP2U1 gene: a c.1288?1G[A splicing mutation (exon 3) and a c.1545_1546delTTAC frameshift mutation (exon 5). The segregation of the mutations in the family was confirmed by DNA analysis of the parents. To prove pathogenicity of the mutations we conducted studies through the Next Generation Sequencing of the cDNA of CYP2U1 extracted from patient fibroblasts, evidenced the absence of the allele containing the 4 bp deletion and a significative exon 3 skipping. Until 14 years of age, our patient did not show the described pigmentary maculopathy on the retina, although she had already developed macular haemorrhagic lesions. Moreover, delayed flashing lights and P100 in visualevoked potentials only appeared after 10 years of age. Differently from our case and the case reported by Leonardi et al. [1], in other descriptions ophthalmological examinations were unremarkable [3, 4], probably because subjects were in the pediatric age, whereas in the cases reported by Tesson et al. no information about ophthalmological features were available [1]. In our patient, normal developmental milestones were reported until 14 months, when her motor skills began to deteriorate rapidly for the first 3 years and subsequently slowed down in progression. Since 16 months of age, she developed four limbs spasticity, more remarkable in the lower limbs, with ‘‘bottom to top’’ progression. After the age of 4 years appeared dysarthria and focal dystonic postures of the upper limbs probably due to the basal ganglia involvement. In the time of the last evaluation at 34 years old, she was on a wheelchair due severe spasticity with joint contractures especially in a lower limbs and presented swallowing difficulties. These appear to be & Alessandro Iodice [email protected]
Frontiers in Neurology | 2017
Mattia Fonderico; Michele Laudisi; Nico Golfrè Andreasi; Stefania Bigoni; Costanza Lamperti; Celeste Panteghini; Barbara Garavaglia; Miryam Carecchio; Elia Antonio Emanuele; Gian Luca Forni; Enrico Granieri
Here, we report the case of a 36-year-old patient with a diagnosis of de novo mutation of the WDR45 gene, responsible for beta-propeller protein-associated neurodegeneration, a phenotypically distinct, X-linked dominant form of Neurodegeneration with Brain Iron Accumulation. The clinical history is characterized by a relatively stable intellectual disability and a hypo-bradykinetic and hypertonic syndrome with juvenile onset. Genetic investigations and T1 and T2-weighted MR images align with what is described in literature. The patient was also subjected to PET with 18-FDG investigation and DaT-Scan study. In reporting relevant clinical data, we want to emphasize the fact that the patient received a chelation therapy with deferiprone (treatment already used in other forms of NBIA with encouraging results), which, however, had to be interrupted because the parkinsonian symptoms worsened. Conversely, the patient has benefited from non-drug therapies and, in particular, from an adapted motor activity with assisted pedaling (method in the process of validation in treatments of parkinsonian syndromes), which started before the treatment with deferiprone and still continues.