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Salvatore Grosso

Publications and source records attributed to Salvatore Grosso.

At least 19 recordsLinked to original sources
PubMed2025

AUTS2-related syndrome: Insights from a large European cohort.

PURPOSE: AUTS2-related syndrome is characterized by developmental delay, autism spectrum disorder, and intellectual disability. From alternative promoters, AUTS2 encodes 2 distinct long and short isoforms encoding a putative transcriptional activator. METHODS: Through a European collaborative study, we collected clinical and genotype data on the largest AUTS2-related syndrome cohort of 58 patients harboring genomic rearrangements or single-nucleotide variants (SNVs). RESULTS: Pathogenic SNVs were recurrently found in individuals from different countries, suggesting mutational hotspots. Independent of the underlying defect at the AUTS2 locus, we observed that autistic behavior, hyperactivity, learning difficulties, and speech delay are common features of AUTS2-related syndrome. Among patients with SNVs, individuals carrying pathogenic variants affecting both longer and shorter AUTS2 transcripts showed a recognizable phenotype with microcephaly, brachycephaly, microretrognathia, broad nasal base, and anteverted nares. Behavioral disorders were more common in patients with variants affecting only the longer isoform. Arthrogryposis and stiff movements were only observed in patients with SNVs. CONCLUSION: This study provides a comprehensive clinical characterization of AUTS2-related syndrome, reveals few genotype-phenotype correlations, and suggests that the disruption of the 2 distinct AUTS2 transcripts has a different impact on the clinical phenotype.

Humans↗
PubMed2006

Photoparoxysmal responses in children with chromosomal aberrations.

Electroencephalographic (EEG) anomalies and epilepsy are commonly observed in the clinical picture of patients with chromosomal aberrations. However, no investigations have been performed on the relationship between chromosomal disorders and photoparoxysmal response (PPR). In this study, we evaluate the characteristics of PPRs elicited with intermittent photic stimulation during a routine electroencephalogram in children affected by chromosomal anomalies and correlated this with the clinical profile of the child. A review of the literature has also been performed. PPRs occurred in 14% (4/28) of patients. PPRs were brief (<less 5s), self-limited, elicited by several series of flashes, with an onset latency between 2 and 9s, and scarcely controlled by anticonvulsants. Although further studies are needed to confirm the present data, our observations and the review of the literature suggest that patients carrying chromosomal anomalies might have a higher risk for photosensitivity when compared to the normal population. In these patients, PPR might occur early in life, persist into adulthood, and is commonly inscribed in more polymorphic electroclinical patterns.

Adolescent↗
PubMed2005

Loss-of-function mutation of the AF9/MLLT3 gene in a girl with neuromotor development delay, cerebellar ataxia, and epilepsy.

The human AF9/MLLT3 gene is a common fusion partner for the MLL gene in translocations t(9;11)(p22;q23) associated with acute myeloid leukemia and acute lymphocytic leukemia. The exact function of the gene is still unknown, although a mouse knock-out model points to a role as a controller of embryo patterning. We report the case of a constitutional translocation t(4;9)(q35;p22) disrupting the AF9/MLLT3 gene in a girl with neuromotor development delay, cerebellar ataxia and epilepsy. Array-CGH analysis at 1 Mbase resolution did not reveal any additional deletions/duplications. We hypothesize a loss-of-function mutation of the AF9/MLLT3 gene, and a possible role for the FAT gene on chromosome 4, in the genesis of the proband's severe neurological phenotype.

Base Sequence↗
PubMed2005

CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome.

Rett syndrome (RTT) is a severe neurodevelopmental disorder almost exclusively affecting females and characterized by a wide spectrum of clinical manifestations. Most patients affected by classic RTT and a smaller percentage of patients with the milder form 'preserved speech variant' have either point mutations or deletions/duplications in the MECP2 gene. Recently, mutations in the CDKL5 gene, coding for a putative kinase, have been found in female patients with a phenotype overlapping with that of RTT. Here, we report two patients with the early seizure variant of RTT, bearing two novel CDKL5 truncating mutations, strengthening the correlation between CDKL5 and RTT. Considering the similar phenotypes caused by mutations in MECP2 and CDKL5, it has been suggested that the two genes play a role in common pathogenic processes. We show here that CDKL5 is a nuclear protein whose expression in the nervous system overlaps with that of MeCP2, during neural maturation and synaptogenesis. Importantly, we demonstrate that MeCP2 and CDKL5 interact both in vivo and in vitro and that CDKL5 is indeed a kinase, which is able to phosphorylate itself and to mediate MeCP2 phosphorylation, suggesting that they belong to the same molecular pathway. Furthermore, this paper contributes to the clarification of the phenotype associated with CDKL5 mutations and indicates that CDKL5 should be analyzed in each patient showing a clinical course similar to RTT but characterized by a lack of an early normal period due to the presence of seizures.

Age of Onset↗
PubMed2005

Non-progressive leukoencephalopathy with bilateral anterior temporal cysts: a case report and review of the literature.

A newly described disease is characterized by anterior bilateral temporal lobe cysts associated with multilobar leukoencephalopathy and a non-progressive clinical course. We report a patient with bilateral anterior temporal lobe cystic changes associated with a non-progressive neurological disorder, microcephaly, spasticity, mental retardation, and sensorineural deafness. From the literature, 12 other patients have shown a similar phenotype. The common neuroradiological findings in these patients have been bilateral anterior temporal lobe cystic changes and non-progressive leukoencephalopathy. By contrast, variability in the clinical phenotype has been observed, ranging from severe neuromotor handicap with mental retardation and microcephaly to spasticity in the lower limbs associated with normal cognitive function. The pathological basis of the defect remains to be defined.

Central Nervous System Cysts↗
PubMed2005

Post-ictal circulating levels of allopregnanolone in children with partial or generalized seizures.

INTRODUCTION: Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) is a neurosteroid with a potent modulating activity on the gamma-aminobutyric acid (GABA)(a) receptor complex. It plays a key role in the epileptogenesis of partial seizures. Serum allopregnanolone concentrations significantly increase in the postcritical phase. In the present study we investigated the post-ictal serum allopregnanolone levels in children with partial seizures and generalized seizures, respectively. PATIENTS AND METHODS: Three groups of subjects were included in the study. Group 1 consisted of 18 children affected by complex partial seizures. Group 2 consisted of 11 children presenting with generalized epilepsy. Group 3 consisted of 20 healthy age-matched subjects. Serum allopregnanolone levels were assayed in the inter-ictal phase and within 30 min after an epileptic event. RESULTS: The data we obtained suggest that circulating allopregnanolone level significantly increases in the post-ictal phase. However, we found no significant differences in the post-ictal serum allopregnanolone concentrations between patients with partial seizures and those with generalized seizures. CONCLUSIONS: Further studies are needed to establish if allopregnanolone is a reliable circulating marker of epileptic seizures. However, our observations seem to indicate that post-ictal circulating allopregnanolone level is not useful in differentiating focal and generalized epilepsy events.

Anesthetics↗
PubMed2005

Childhood absence epilepsy: evolution and prognostic factors.

PURPOSE: To evaluate how diagnostic criteria influence remission rates for patients with childhood absence epilepsy (CAE) and to assess clinical and EEG parameters as predictors of outcome. METHODS: One hundred nineteen patients were diagnosed with CAE, according to International League Against Epilepsy (ILAE) classification criteria. They were subsequently evaluated according to stricter diagnostic criteria. Sixty-two subjects fulfilled these criteria as group 2; 57 did not and constituted group 1. Diagnostic parameters that prevented patients of group 1 from entering group 2, and variables such as sex, familial history of generalized epilepsy, and personal history of febrile convulsions also were tested as prognostic factors for terminal remission. RESULTS: Compared with those in group 1, patients of group 2 had significantly higher rates of seizure control (95% vs. 77%), higher rates of terminal remission (82% vs. 51%), fewer generalized tonic-clonic seizures (8% vs. 30%), and shorter mean periods of treatment (2.2 vs. 3.8 years). Significantly fewer patients were receiving polytherapy in group 2 than in group 1 (11% vs. 47%), and fewer patients had seizure relapses at antiepileptic drug discontinuation (0 vs. 22%). CONCLUSIONS: Remission rates of patients with CAE are greatly influenced by the classification criteria used for selection. Stricter diagnostic criteria allow the definition of a homogeneous group of patients with excellent prognosis. Factors predicting unfavorable prognosis were generalized tonic-clonic seizures in the active stage of absences, myoclonic jerks, eyelid myoclonia or perioral myoclonia, and EEG features atypical for CAE.

Adolescent↗
PubMed2005

Efficacy and safety of topiramate in refractory epilepsy of childhood: long-term follow-up study.

This study aimed to evaluate the long-term efficacy and safety of topiramate in treating children with drug-resistant epilepsy. A multicentric, retrospective, open-label, add-on study was undertaken of 277 children (mean age 8.4 years; range 12 months to 16 years) affected by drug-resistant epilepsy. The efficacy was rated according to the seizure types and epilepsy syndrome. After a mean period of 27.5 months of treatment (range 24-61 months), 11 patients (4%) were seizure free and 56 (20%) had more than 50% reduction in seizure frequency. The efficacy of topiramate treatment was noted in localization-related epilepsy and in generalized epilepsy. In addition, in a group of 114 patients, we compared the initial efficacy (evaluated after a mean of 9 months of follow-up) and the retention at a mean of 30 months of topiramate with regard to loss of efficacy (defined as the return to the baseline seizure frequency). Fifty-five (48%) of 114 patients were initial responders. The retention at a mean of 30 months was 23 of 114 patients (20%), 4 of whom (3.5%) were still seizure free. A loss of efficacy occurred in 32 of the 55 initial responders (58%). It was prominent in patients with generalized epilepsy, such as symptomatic infantile spasms and Lennox-Gastaut syndrome, as well as in those with Dravet syndrome. By contrast, a well-sustained topiramate efficacy was noted among patients with localization-related epilepsy. Globally, adverse events were observed in 161 patients (58%) and were mainly represented by weight loss, hyperthermia, sedation, and nervousness, which, in most cases, disappeared after slowing titration or reducing the dosage of the drug. In conclusion, the present long-term study confirms that topiramate represents a useful drug effective in a wide range of seizures and epilepsy syndromes. Moreover, preliminary data seem to suggest that the efficacy of topiramate, when evaluated in the long-term perspective, is more sustained in localization-related epilepsy than in generalized epilepsy.

Adolescent↗
PubMed2004

Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria.

d-2-hydroxyglutaric aciduria is a neurometabolic disorder with both a mild and a severe phenotype and with unknown etiology. Recently, a novel enzyme, d-2-hydroxyglutarate dehydrogenase, which converts d-2-hydroxyglutarate into 2-ketoglutarate, and its gene were identified. In the genes of two unrelated patients affected with d-2-hydroxyglutaric aciduria, we identified disease-causing mutations. One patient was homozygous for a missense mutation (c.1331T-->C; p.Val444Ala). The other patient was compound heterozygous for a missense mutation (c.440T-->G; p.Ile147Ser) and a splice-site mutation (IVS1-23A-->G) that resulted in a null allele. Overexpression studies in HEK-293 cells of proteins containing the missense mutations showed a marked reduction of d-2-hydroxyglutarate dehydrogenase activity, proving that mutations in the d-2-hydroxyglutarate dehydrogenase gene cause d-2-hydroxyglutaric aciduria.

Alcohol Oxidoreductases↗
PubMed2004

Craniofacial dyssynostosis: case report and review.

Craniofacial dyssynostosis (CFD) is a rare disorder related to premature closure of the lambdoid suture and the posterior part of the sagittal suture. Epilepsy, mental retardation, abnormalities of the corpus callosum, and short stature have been reported. We studied a patient with CFD, hydronephrosis, and partially empty sella turcica; the latter two features are reported for the first time. We discuss the brain anomalies and their neurologic sequelae, which are part of the CFD phenotype.

Abnormalities, Multiple↗
PubMed2004

Hot water epilepsy and focal malformation of the parietal cortex development.

Hot water epilepsy (HWE) refers to a specific type of reflex epilepsy precipitated by the stimulus of bathing in hot water. HWE is considered to be a geographically specific epileptic syndrome since it mainly occurs in the Indian community. Spontaneous seizures may also occur later in life. The seizure pattern includes complex partial attacks. Although the pathogenesis of HWE is still unknown, temporal lobe has been thought to take part in the epileptogenesis. This paper reports on a 4-year-old girl who, at the age of 6 months, experienced complex partial seizures triggered by bathing in hot water. Non-provoked seizures intercritical EEG showed isolated spikes and spike-and-waves in the left parietal region. Brain MRI detected a left parietal focal cortical dysplasia. This is the second patient with HWE in whom a cortical malformation has been observed. The observation present here and data reported in the literature seem to indicate that the sensory cortex might also be involved in triggering seizures precipitated by a bath in hot water. Moreover, the authors believe that MRI examination should be considered for this group of patients.

Anticonvulsants↗
PubMed2004

Epilepsy and electroencephalographic findings in pericentric inversion of chromosome 12.

Epilepsy, together with mental retardation, represents a common manifestation of chromosomal aberrations. Specific electroencephalographic (EEG) and epileptic patterns have been described in several chromosomal disorders, such as Angelman's syndrome, Miller-Dieker syndrome, Wolf-Hirschhorn syndrome, and ring 20 syndrome. A peculiar electroclinical pattern has also been identified in trisomy 12p syndrome. We report three patients with a pericentric inversion of chromosome 12, with breakpoints localized to p11-q13 and affected by epilepsy or EEG anomalies. Two suffered from epilepsy, which, in the clinical course, was mainly characterized by complex partial seizures with a semiology related to the temporal lobe. In one patient, myoclonic absences, head drop, and massive jerky attacks were also present. In both patients, generalized 3 Hz bursts were registered, together with multifocal and focal paroxysmal activity, which were most prominent in the temporoparietal and temporal areas, respectively. In the other patient, who had no epilepsy, EEG showed bioccipital paroxysmal activity. In all patients, the clinical picture was characterized by the presence of moderate mental retardation and behavioral disorders. The incidence of epilepsy or EEG anomalies among patients with a pericentric inversion of chromosome 12 remains to be ascertained. However, the present study confirms that chromosome 12 anomalies can be associated with epilepsy. Although myoclonic absence-like episodes can occasionally be part of the epileptic phenotype, the electroclinical pattern in pericentric inversion of chromosome 12 seems to be more polymorphic when compared with that observed in trisomy 12p syndrome.

Adult↗
PubMed2003

Medial temporal lobe dysgenesis in Muenke syndrome and hypochondroplasia.

Hypochondroplasia (HCH) and Muenke syndrome (MS) are caused by mutations on FGFR3 gene. FGFR3 is known to play a role in controlling nervous system development. We describe the clinical and neuroradiological findings of the first two patients, to our knowledge, affected by HCH and MS, respectively, in whom bilateral dysgenesis of the medial temporal lobe structures has been observed. In both patients diagnosis was confirmed by molecular analysis. They were mentally normal and showed similarities in early-onset temporal lobe-related seizures. In both patients EEG recorded bilateral temporal region discharges. MRI detected temporal lobe anomalies with inadequate differentiation between white and gray matter, defective gyri, and abnormally shaped hippocampus.

Abnormalities, Multiple↗
PubMed2003

Molecular analysis of the GNAS1 gene for the correct diagnosis of Albright hereditary osteodystrophy and pseudohypoparathyroidism.

Pseudohypoparathyroidism (PHP) is a heterogeneous disease characterized by PTH resistance and classified as types Ia, Ib, Ic, and II, according to its different pathogenesis and phenotype. PHP-Ia patients show Gsalpha protein deficiency, PTH resistance, and typical Albright hereditary osteodystrophy (AHO). Heterozygous mutations in the GNAS1 gene encoding the Gsalpha protein have been identified both in PHP-Ia and in pseudopseudohypoparathyroidism (PPHP), a disorder with isolated AHO. A single GNAS1 mutation may be responsible for both PHP-Ia and PPHP in the same family when inherited from the maternal and the paternal allele, respectively, suggesting that GNAS1 is an imprinted gene. To evaluate whether molecular diagnosis is a useful tool to characterize AHO and PHP when testing for Gsalpha activity and PTH resistance is not available, we have performed GNAS1 mutational analysis in 43 patients with PTH resistance and/or AHO. Sequencing of the whole coding region of the GNAS1 gene identified 11 mutations in 18 PHP patients, eight of which have not been reported previously. Inheritance was ascertained in 13 cases, all of whom had PHP-Ia: the mutated alleles were inherited from the mothers, who had AHO (PPHP), consistent with the proposed imprinting mechanism. GNAS1 molecular analysis confirmed the diagnosis of PHP-Ia and PPHP in the mutated patients. Our results stress the usefulness of this approach to obtain a complete diagnosis, expand the GNAS1 mutation spectrum, and illustrate the wide mutation heterogeneity of PHP and PHP-Ia.

Adolescent↗
PubMed2003

GM2 gangliosidosis variant B1 neuroradiological findings.

Variant B1 is a rare type of GM2 gangliosidosis. Clinically, it shows a wide spectrum of forms ranging from infantile to juvenile. We report the first magnetic resonance imaging (MRI) findings from three patients affected by GM2 gangliosidosis variant B1, two presenting with the infantile form and one with the juvenile form. The MRI appearances of the two patients with the infantile form disease are congruent with those reported for the early-onset type of both Tay-Sachs and Sandhoff diseases, and are characterized by early involvement of the basal ganglia and thalamus with cortical atrophy appearing later. In contrast, the patient with the juvenile form of variant B1 showed progressive cortical and white-matter atrophy of the supratentorial structures and, to a lesser extent, the infratentorial structures. No basal ganglia or thalamic anomalies were observed. Because in the adult forms of both Tay-Sachs and Sandhoff diseases a progressive cerebellar atrophy represents the only abnormality detectable, it appears that an MRI pattern peculiar to GM2 gangliosidosis can be defined. This pattern ranges from the basal ganglia injury associated with the early and severe demyelination process noted in the infantile form of the disease, to cerebellar atrophy with no supratentorial anomalies in the adult form. An "intermediate" MRI picture, with cortical atrophy and mild cerebellar atrophy, but without basal ganglia impairment, can be observed in the juvenile form. In addition, our investigations suggest that MRI abnormalities in GM2 gangliosidosis correlate with the clinical form of the disease rather than with the biochemical variant of the enzymatic defect.

Age Factors↗
PubMed2003

Linear scleroderma associated with progressive brain atrophy.

Linear scleroderma (LS) is characterized by scleroatrophic lesions affecting limbs and legs, unilaterally. Neurological involvement may be associated with ipsilateral facial and skull involvement in disorders referred to clinically as LS 'en coup de sabre', and Parry-Romberg syndrome. We report a child with LS presenting with a severe neurological disorder characterized by epilepsy, progressive mental deterioration and a rapid process of atrophy involving the ipsilateral cerebral hemisphere, but not associated with an overlying facial structure involvement. Functional brain studies showed a reduction in the diameter of the left internal carotid and of the left middle cerebral artery. Our observations suggest that neuroimaging studies should be considered in all patients with linear scleroderma, and such studies become necessary when neurological symptoms occur.

Brain Diseases↗
PubMed2003

Schinzel-Giedion syndrome: a further cause of West syndrome.

Schinzel-Giedion syndrome (SGS) is a rare disorder with a likely autosomal recessive pattern of inheritance which is characterized by several facial dysmorphisms, midface hypoplasia, multiple skeletal anomalies including short and sclerotic skull base, short neck, and post-axial polydactyly. Cardiac and urogenital malformations are also present. Thirty-three cases have been described so far. We report on a boy affected by SGS in whom a long-term EEG follow-up showed a progressive deterioration of the background bioelectric activity ending, at the age of 19 months, with a hypsarrhythmic pattern clinically correlated with severe and refractory infantile spasms. EEG deterioration and neuroradiological findings, which showed progressive brain atrophy, confirm the neurodegenerative nature of SGS. We also re-evaluated all the published cases and found that 33% of patients with SGS experienced neonatal seizures and another 25% developed West syndrome in the following months. The seizures appeared extremely refractory to several anticonvulsive treatments. In conclusion, we believe that SGS should be included among the causes of secondary West syndrome.

Abnormalities, Multiple↗