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1.
Cerebellum ; 18(5): 972-975, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31410782

RESUMO

Spinocerebellar Ataxia 23 (SCAR23) is a newly described condition caused by mutations in TDP2 gene. To date, only four patients from two families have been reported, all carrying the same homozygous mutation. We describe a fifth patient, carrying a novel mutation in the same gene, thus confirming the role of TDP2 mutations in determining the disease and defining the main features SCAR23: pediatric onset ataxia and drug-resistant epilepsy and intellectual disability. We further show the clinical presentation which is associated with the neuroradiological evidence of progressive cerebellar atrophy, giving the evidence that SCAR23 can be classified as a degenerative condition.

3.
Mol Genet Metab ; 126(4): 489-494, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30826161

RESUMO

BACKGROUND: Aicardi-Goutières syndrome (AGS) is a rare genetic leukoencephalopathy related to inappropriate activation of type I interferon. Neuroradiological findings are typically characterized by white matter abnormalities, cerebral atrophy and cerebral calcification. The disease usually manifests itself during the first year of life in the form of an initial "encephalitic-like" phase followed by a chronic phase of stabilization of the neurological signs. Recently new therapeutic strategies have been proposed aimed at blocking the abnormal activation of the interferon cascade. MATERIALS AND METHODS: We reviewed clinical and MRI findings in three young RNASEH2B-mutated patients studied with serial CT and MRI studies. RESULTS: All three patients presented clinical and MRI features consistent with AGS but, very unexpectedly, an improving neuroradiological course. In patient 1, the MRI improvement was noted some months after treatment with high-dose steroid and IVIg treatment; in patients 2 and 3 it occurred spontaneously. Patient 2 did not show cerebral calcification on CT images. CONCLUSIONS: Our series highlights the possibility of spontaneous neuroradiological improvement in AGS2 patients, as well as the possibility of absence of cerebral calcification in AGS. The study underlines the need for extreme caution when using MRI as an outcome measure in therapeutic trials specific for this disease. MRI follow-up studies in larger series are necessary to describe the natural course of AGS.

4.
Am J Med Genet A ; 179(4): 588-594, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30793471

RESUMO

Overgrowth-intellectual disability (OGID) syndromes are characterized by increased growth (height and/or head circumference ≥+2 SD) in association with an intellectual disability. Constitutive EED variants have previously been reported in five individuals with an OGID syndrome, eponymously designated Cohen-Gibson syndrome and resembling Weaver syndrome. Here, we report three additional individuals with constitutive EED variants, identified through exome sequencing of an OGID patient series. We compare the EED phenotype with that of Weaver syndrome (56 individuals), caused by constitutive EZH2 variants. We conclude that while there is considerable overlap between the EED and EZH2 phenotypes with both characteristically associated with increased growth and an intellectual disability, individuals with EED variants more frequently have cardiac problems and cervical spine abnormalities, boys have cryptorchidism and the facial gestalts can usually be distinguished.

5.
Eur J Med Genet ; 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30528446

RESUMO

OBJECTIVE OF THE STUDY: To give a full overview of the clinical presentation of PTEN mutations in pediatric patients and to propose a pediatric follow-up protocol. METHODS: Recruitment of 16 PTEN mutated children (age 6 months-11 years) from two pediatric centers in Milan (Italy) between 2006 and 2017. All the patients underwent clinical and neurologic evaluations, cognitive and behavioral tests, and brain MRI; they are currently following an oncologic follow-up. RESULTS: Extreme macrocephaly is present in all the patients (69% HC above +4 SD). Neuropsychiatric issues have high prevalence, with 56% of patients showing developmental delay and 25% showing autism spectrum disorder. Brain MRI reveals in 75% of the patients at least one of the following: enlarged perivascular spaces, white matter anomalies, and/or downward displacement of the cerebellar tonsils through the foramen magnum, resulting in Chiari I malformation in two patients. Vascular malformations have a prevalence of 19%, with further evidence that complex cardiovascular malformations may be related to PTEN mutations; 31% of patients present hamartomas. None of our patients have so far experienced any oncologic complication. CONCLUSIONS: We suggest to screen for PTEN mutations all children presenting macrocephaly and one of the following: neurodevelopmental issues, one of the three major brain MRI anomalies, cutaneous lesions, vascular malformations, family history positive for PTEN related malignancies; or also with macrocephaly alone when exceeding +3 SD. Basing on our cohort results and further recent studies on the condition, we recommend a follow-up protocol that includes annual clinical and dermatological examination, thyroid and abdominal US, and Fecal Occult Blood test plus neurodevelopmental evaluation, heart US (to exclude congenital heart malformations), and brain MRI (to exclude Chiari I malformation) at diagnosis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30403813

RESUMO

Background: Joubert syndrome (JS) is an inherited ciliopathy characterized by a complex midbrain-hindbrain malformation and multiorgan involvement. Renal disease, mainly juvenile nephronophthisis (NPH), was reported in 25-30% patients although only ∼18% had a confirmed diagnosis of chronic kidney disease (CKD). NPH often remains asymptomatic for many years, resulting in delayed diagnosis. The aim of the study was to identify a biomarker able to quantify the risk of progressive CKD in young children with JS. Methods: Renal features were investigated in 93 Italian patients, including biochemical tests, ultrasound and 1-deamino-8D-arginine vasopressin test in children with reduced basal urine osmolality. A subset of patients was followed-up over time. Results: At last examination, 27 of 93 subjects (29%) presented with CKD, ranging from isolated urinary concentration defect (UCD) to end-stage renal disease. Both normal and pathological urine osmolality levels remained stable over time, even when obtained at very early ages. Follow-up data showed that the probability of developing CKD can be modelled as a function of the urine osmolality value, exceeding 75% for levels <600 mOsm/kg H2O, and significantly increased in patients with an early diagnosis of isolated UCD. Conclusions: We conclude that the frequency of CKD in JS increases with age and is higher than previously reported. Urine osmolality represents an early sensitive quantitative biomarker of the risk of CKD progression.

7.
Am J Med Genet B Neuropsychiatr Genet ; 177(6): 557-562, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30105822

RESUMO

The presence of redundant copy number variants (CNVs) in groups of patients with neurological diseases suggests that these variants could have pathogenic effect. We have collected array comparative genomic hybridization (CGH) data of about 2,500 patients affected by neurocognitive disorders and we observed that CNVs in 2p16.3 locus were as frequent as those in 15q11.2, being both the most frequent unbalances in our cohort of patients. Focusing to 2p16.3 region, unbalances involving NRXN1 coding region have been already associated with neuropsychiatric disorders, although with incomplete penetrance, but little is known about CNVs located proximal to the gene, in the long noncoding RNA AK127244. We found that, in our cohort of patients with neuropsychiatric disorders, the frequency of CNVs involving AK127244 was comparable to that of NRXN1 gene. Patients carrying 2p16.3 unbalances shared some common clinical characteristics regardless NRXN1 and AK127244 CNVs localization, suggesting that the AK127244 long noncoding RNA could be involved in neurocognitive disease with the same effect of NRXN1 unbalances. AK127244 as well as NRXN1 unbalances seem to have a particular influence on language development, behavior or mood, according with the topographic correlation between NRXN1 expression and prefrontal cortex functions.

8.
Handb Clin Neurol ; 154: 167-180, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29903438

RESUMO

The question posed today is not whether the cerebellum plays a role in cognition, but instead, how the cerebellum contributes to cognitive processes, even in the developmental age. The central role of the cerebellum in many areas of human abilities, motor as well as cognitive, in childhood as well as in adulthood, is well established but cerebellar basic functioning is still not clear and is much debated. Of particular interest is the changing face of cerebellar influence on motor, higher cognitive, and behavioral functioning when adult and developmental lesions are compared. The idea that the cerebellum might play quite different roles during development and in adulthood has been proposed, and evidence from experimental and clinical literature has been provided, including for sequencing, behavioral aspects, and executive functions Still, more data are needed to fully understand the changes of cerebrocerebellar interactions within the segregated loops which connect cerebrum and cerebellum, not only between childhood and adulthood but also in health and disease.


Assuntos
Cerebelo/fisiologia , Cognição/fisiologia , Função Executiva/fisiologia , Doenças Cerebelares/complicações , Cerebelo/patologia , Humanos , Transtornos do Neurodesenvolvimento/patologia
10.
Am J Hum Genet ; 101(4): 552-563, 2017 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-28965847

RESUMO

The Sonic Hedgehog (SHH) pathway is a key signaling pathway orchestrating embryonic development, mainly of the CNS and limbs. In vertebrates, SHH signaling is mediated by the primary cilium, and genetic defects affecting either SHH pathway members or ciliary proteins cause a spectrum of developmental disorders. SUFU is the main negative regulator of the SHH pathway and is essential during development. Indeed, Sufu knock-out is lethal in mice, and recessive pathogenic variants of this gene have never been reported in humans. Through whole-exome sequencing in subjects with Joubert syndrome, we identified four children from two unrelated families carrying homozygous missense variants in SUFU. The children presented congenital ataxia and cerebellar vermis hypoplasia with elongated superior cerebellar peduncles (mild "molar tooth sign"), typical cranio-facial dysmorphisms (hypertelorism, depressed nasal bridge, frontal bossing), and postaxial polydactyly. Two siblings also showed polymicrogyria. Molecular dynamics simulation predicted random movements of the mutated residues, with loss of the native enveloping movement of the binding site around its ligand GLI3. Functional studies on cellular models and fibroblasts showed that both variants significantly reduced SUFU stability and its capacity to bind GLI3 and promote its cleavage into the repressor form GLI3R. In turn, this impaired SUFU-mediated repression of the SHH pathway, as shown by altered expression levels of several target genes. We demonstrate that germline hypomorphic variants of SUFU cause deregulation of SHH signaling, resulting in recessive developmental defects of the CNS and limbs which share features with both SHH-related disorders and ciliopathies.


Assuntos
Anormalidades Múltiplas/genética , Doenças do Desenvolvimento Ósseo/genética , Cerebelo/anormalidades , Anormalidades Craniofaciais/genética , Anormalidades do Olho/genética , Genes Recessivos , Proteínas Hedgehog/metabolismo , Doenças Renais Císticas/genética , Mutação de Sentido Incorreto , Proteínas Repressoras/genética , Retina/anormalidades , Anormalidades Múltiplas/patologia , Doenças do Desenvolvimento Ósseo/patologia , Células Cultivadas , Cerebelo/patologia , Criança , Estudos de Coortes , Anormalidades Craniofaciais/patologia , Anormalidades do Olho/patologia , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Doenças Renais Císticas/patologia , Fatores de Transcrição Kruppel-Like/metabolismo , Masculino , Proteínas do Tecido Nervoso/metabolismo , Proteínas Repressoras/química , Proteínas Repressoras/metabolismo , Retina/patologia , Análise de Sequência de DNA , Transdução de Sinais , Pele/metabolismo , Pele/patologia , Proteína Gli3 com Dedos de Zinco
12.
Eur Radiol ; 27(12): 5080-5092, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28677066

RESUMO

OBJECTIVE: To determine the neuroimaging pattern of cerebellar dysplasia (CD) and other posterior fossa morphological anomalies associated with mutations in tubulin genes and to perform clinical and genetic correlations. METHODS: Twenty-eight patients harbouring 23 heterozygous pathogenic variants (ten novel) in tubulin genes TUBA1A (n = 10), TUBB2B (n = 8) or TUBB3 (n = 5) were studied by a brain MRI scan performed either on a 1.5 T (n = 10) or 3 T (n = 18) MR scanner with focus on the posterior fossa. RESULTS: Cerebellar anomalies were detected in 24/28 patients (86%). CD was recognised in 19/28 (68%) including cortical cerebellar dysplasia (CCD) in 18/28, either involving only the cerebellar hemispheres (12/28) or associated with vermis dysplasia (6/28). CCD was located only in the right hemisphere in 13/18 (72%), including four TUBB2B-, four TUBB3- and five TUBA1A-mutated patients, while in the other five TUBA1A cases it was located only in the left hemisphere or in both hemispheres. The postero-superior region of the cerebellar hemispheres was most frequently affected. CONCLUSIONS: The cerebellar involvement in tubulinopathies shows specific features that may be labelled as 'tubulin-related CD'. This pattern is unique and differs from other genetic causes of cerebellar dysplasia. KEY POINTS: • Cortical cerebellar dysplasia without cysts is suggestive of tubulin-related disorder. • Cerebellar dysplasia in tubulinopathies shows specific features labelled as 'tubulin-related CD'. • Focal and unilateral involvement of cerebellar hemispheres has important implications for counselling.


Assuntos
Cerebelo/anormalidades , Mutação , Malformações do Sistema Nervoso/diagnóstico por imagem , Neuroimagem/métodos , Tubulina (Proteína)/genética , Adulto , Tronco Encefálico/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Feminino , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/patologia , Adulto Jovem
14.
Am J Med Genet A ; 173(5): 1358-1363, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28345801

RESUMO

ZC4H2 is involved in human brain development, and, if mutated, can be responsible for a rare X-linked disorder, originally presented in literature as Wieacker-Wolff syndrome and Miles-Carpenter syndrome. In males, severe intellectual disability is associated with variable symptoms of central and peripheral nervous system involvement, such as spasticity, hyperreflexia, muscle weakness, and arthrogryposis. Female carriers are usually described as asymptomatic or only mildly affected. Here, we report on a girl carrying a de novo deletion of ZC4H2 detected by array-CGH analysis. She showed a complex neurodevelopmental disorder resembling the clinical picture commonly observed in male patients. X-inactivation was found to be random. Additionally, she had an unusual appearance of fingers and hand creases, and electromyography showed a peculiar pattern of both neurogenic and myopathic anomalies. The present patient confirms that female carriers can also be severely affected. Systematic clinical investigations of both males and females are needed to define the variety in nature and severity of phenotypes related to ZC4H2 variants.


Assuntos
Apraxias/genética , Proteínas de Transporte/genética , Contratura/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Deficiência Intelectual/genética , Retardo Mental Ligado ao Cromossomo X/genética , Retardo Mental Ligado ao Cromossomo X/psicologia , Atrofia Muscular/genética , Oftalmoplegia/genética , Adolescente , Apraxias/diagnóstico , Apraxias/fisiopatologia , Criança , Hibridização Genômica Comparativa , Contratura/diagnóstico , Contratura/fisiopatologia , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/fisiopatologia , Masculino , Retardo Mental Ligado ao Cromossomo X/diagnóstico , Retardo Mental Ligado ao Cromossomo X/fisiopatologia , Atrofia Muscular/diagnóstico , Atrofia Muscular/fisiopatologia , Oftalmoplegia/diagnóstico , Oftalmoplegia/fisiopatologia , Deleção de Sequência
15.
Am J Med Genet A ; 170(12): 3115-3124, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27530364

RESUMO

Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by a distinctive cerebellar and brainstem malformation recognizable on brain imaging, the so-called molar tooth sign. The full spectrum of cognitive and behavioral phenotypes typical of JS is still far from being elucidated. The aim of this multicentric study was to define the clinical phenotype and neurobehavioral features of a large cohort of subjects with a neuroradiologically confirmed diagnosis of JS. Fifty-four patients aged 10 months to 29 years were enrolled. Each patient underwent a neurological evaluation as well as psychiatric and neuropsychological assessments. Global cognitive functioning was remarkably variable with Full IQ/General Quotient ranging from 32 to 129. Communication skills appeared relatively preserved with respect to both Daily Living and Socialization abilities. The motor domain was the area of greatest vulnerability, with a negative impact on personal care, social, and academic skills. Most children did not show maladaptive behaviors consistent with a psychiatric diagnosis but approximately 40% of them presented emotional and behavioral problems. We conclude that intellectual disability remains a hallmark but cannot be considered a mandatory diagnostic criterion of JS. Despite the high variability in the phenotypic spectrum and the extent of multiorgan involvement, nearly one quarter of JS patients had a favorable long-term outcome with borderline cognitive deficit or even normal cognition. Most of JS population also showed relatively preserved communication skills and overall discrete behavioral functioning in everyday life, independently from the presence and/or level of intellectual disability. © 2016 Wiley Periodicals, Inc.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/fisiopatologia , Cerebelo/anormalidades , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/fisiopatologia , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/fisiopatologia , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/fisiopatologia , Retina/anormalidades , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/psicologia , Adolescente , Adulto , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Criança , Pré-Escolar , Cognição/fisiologia , Emoções/fisiologia , Anormalidades do Olho/diagnóstico por imagem , Anormalidades do Olho/psicologia , Feminino , Humanos , Lactente , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/psicologia , Doenças Renais Císticas/diagnóstico por imagem , Doenças Renais Císticas/psicologia , Imagem por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Fenótipo , Retina/diagnóstico por imagem , Retina/fisiopatologia
16.
J Med Genet ; 53(9): 608-15, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27208211

RESUMO

BACKGROUND: Ciliopathies are an extensive group of autosomal recessive or X-linked disorders with considerable genetic and clinical overlap, which collectively share multiple organ involvement and may result in lethal or viable phenotypes. In large numbers of cases the genetic defect remains yet to be determined. The aim of this study is to describe the mutational frequency and phenotypic spectrum of the CEP120 gene. METHODS: Exome sequencing was performed in 145 patients with Joubert syndrome (JS), including 15 children with oral-facial-digital syndrome type VI (OFDVI) and 21 Meckel syndrome (MKS) fetuses. Moreover, exome sequencing was performed in one fetus with tectocerebellar dysraphia with occipital encephalocele (TCDOE), molar tooth sign and additional skeletal abnormalities. As a parallel study, 346 probands with a phenotype consistent with JS or related ciliopathies underwent next-generation sequencing-based targeted sequencing of 120 previously described and candidate ciliopathy genes. RESULTS: We present six probands carrying nine distinct mutations (of which eight are novel) in the CEP120 gene, previously found mutated only in Jeune asphyxiating thoracic dystrophy (JATD). The CEP120-associated phenotype ranges from mild classical JS in four patients to more severe conditions in two fetuses, with overlapping features of distinct ciliopathies that include TCDOE, MKS, JATD and OFD syndromes. No obvious correlation is evident between the type or location of identified mutations and the ciliopathy phenotype. CONCLUSION: Our findings broaden the spectrum of phenotypes caused by CEP120 mutations that account for nearly 1% of patients with JS as well as for more complex ciliopathy phenotypes. The lack of clear genotype-phenotype correlation highlights the relevance of comprehensive genetic analyses in the diagnostics of ciliopathies.


Assuntos
Anormalidades Múltiplas/genética , Proteínas de Ciclo Celular/genética , Cerebelo/anormalidades , Anormalidades do Olho/genética , Doenças Renais Císticas/genética , Mutação/genética , Retina/anormalidades , Sequência de Aminoácidos , Doenças Cerebelares/genética , Criança , Ciliopatias/genética , Encefalocele/genética , Feminino , Estudos de Associação Genética/métodos , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Humanos , Masculino , Taxa de Mutação , Síndromes Orofaciodigitais/genética , Linhagem , Fenótipo , Alinhamento de Sequência
17.
Am J Med Genet A ; 170A(1): 148-55, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26437767

RESUMO

Seizures are rarely reported in Williams-Beuren syndrome (WBS)--a contiguous-gene-deletion disorder caused by a 7q11.23 heterozygous deletion of 1.5-1.8 Mb--and no previous study evaluated electro-clinical features of epilepsy in this syndrome. Furthermore, it has been hypothesized that atypical deletion (e.g., larger than 1.8 Mb) may be responsible for a more pronounced neurological phenotypes, especially including seizures. Our objectives are to describe the electro-clinical features in WBS and to correlate the epileptic phenotype with deletion of the 7q11.23 critical region. We evaluate the electro-clinical features in one case of distal 7q11.23 deletion syndrome and in eight epileptic WBS (eWBS) patients. Additionally, we compare the deletion size-and deleted genes-of four epileptic WBS (eWBS) with that of four non-epileptic WBS (neWBS) patients. Infantile spasms, focal (e.g., motor and dyscognitive with autonomic features) and generalized (e.g., tonic-clonic, tonic, clonic, myoclonic) seizures were encountered. Drug-resistance was observed in one patient. Neuroimaging discovered one case of focal cortical dysplasia, one case of fronto-temporal cortical atrophy and one case of periventricular nodular heterotopia. Comparison of deletion size between eWBS and neWBS patients did not reveal candidate genes potentially underlying epilepsy. This is the largest series describing electro-clinical features of epilepsy in WBS. In WBS, epilepsy should be considered both in case of typical and atypical deletions, which do not involve HIP1, YWHAG or MAGI2.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Epilepsia/etiologia , Síndrome de Williams/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Epilepsia/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Síndrome de Williams/complicações , Síndrome de Williams/patologia , Adulto Jovem
18.
J Child Neurol ; 31(6): 691-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26511719

RESUMO

Microarray-based comparative genomic hybridization is a method of molecular analysis that identifies chromosomal anomalies (or copy number variants) that correlate with clinical phenotypes. The aim of the present study was to apply a clinical score previously designated by de Vries to 329 patients with intellectual disability/developmental disorder (intellectual disability/developmental delay) referred to our tertiary center and to see whether the clinical factors are associated with a positive outcome of aCGH analyses. Another goal was to test the association between a positive microarray-based comparative genomic hybridization result and the severity of intellectual disability/developmental delay. Microarray-based comparative genomic hybridization identified structural chromosomal alterations responsible for the intellectual disability/developmental delay phenotype in 16% of our sample. Our study showed that causative copy number variants are frequently found even in cases of mild intellectual disability (30.77%). We want to emphasize the need to conduct microarray-based comparative genomic hybridization on all individuals with intellectual disability/developmental delay, regardless of the severity, because the degree of intellectual disability/developmental delay does not predict the diagnostic yield of microarray-based comparative genomic hybridization.


Assuntos
Hibridização Genômica Comparativa/métodos , Variações do Número de Cópias de DNA/genética , Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Aberrações Cromossômicas , Deficiências do Desenvolvimento/diagnóstico por imagem , Eletroencefalografia , Feminino , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/diagnóstico por imagem , Modelos Logísticos , Masculino , Análise em Microsséries , Estudos Retrospectivos , Índice de Gravidade de Doença
19.
Eur J Paediatr Neurol ; 20(1): 183-7, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26565673

RESUMO

INTRODUCTION: 17q21.31 microduplication syndrome is a recently described condition associated with a broad clinical spectrum, of which psychomotor delay, behavioral disorders and poor social interaction seem to be the most consistent features. Only seven patients have been reported thus far. All have behavioral disorders reminiscent of the autistic spectrum with intellectual skills ranging from normal to mild intellectual deficiency. Other features are variable with no striking common phenotypic features. CASE STUDY: Here we describe the segregation of 17q21.31 duplication in an Italian family. DISCUSSION: Clinical features and genetic data are reported, and compared with previously reported patients with 17q21.31 microduplication. A comparison of clinical manifestations between deletion and duplication syndromes of the chromosome regione is provided.


Assuntos
Duplicação Cromossômica/genética , Cromossomos Humanos Par 17/genética , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Itália , Masculino , Linhagem , Fenótipo , Síndrome
20.
J Child Neurol ; 30(13): 1824-30, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25944474

RESUMO

Electroencephalographic (EEG) photoparoxysmal response has been little investigated in very young patients. We studied 5055 patients aged less than 5 years with no acquired brain damage, who underwent EEG recording. We determined the prevalence and significance of photoparoxysmal response induced by 1 to 20 Hz photic stimulation. Fifty-three showed photoparoxysmal response and were diagnosed as having Dravet syndrome (11), epileptic encephalopathy with myoclonic seizures (8), neurodegenerative disorders (8), benign idiopathic epilepsies (9), and static disorders with a known or suspected genetic origin (17). Photoparoxysmal response occurred in response to 1 to 5 Hz trains in 41.5% subjects. In most patients with epileptic encephalopathies, photoparoxysmal response was a transient finding: in 53.2%, it failed to be replicated in the recordings performed more than 6 months after initial evaluation. Photoparoxysmal response is rare in patients aged less than 5 years and has some peculiarities such as occurrence with low-frequency stimuli. Its distribution in specific conditions indicates that photoparoxysmal response may be useful in diagnostic workup.


Assuntos
Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Estimulação Luminosa/métodos , Pré-Escolar , Epilepsias Mioclônicas/diagnóstico , Epilepsias Mioclônicas/fisiopatologia , Seguimentos , Humanos
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