Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved our ability to detect cryptic unbalanced rearrangements in patients with syndromic mental retardation.
...Molecular karyotyping of six patients with syndromic mental retardation was carried out using whole-genome oligonucleotide array-CGH.
5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe mental retardation with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified.
Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations.
Intrauterine transfusion (IUT) has changed fetal anemia prognosis. However, long-term neurodevelopmental outcome is altered in 5% of children. Our objective was to study the contribution of fetal MRI ...to diagnosis brain lesions in case of fetal anemia.
Material and Methods: Retrospective monocentric descriptive study from 2005 to 2016, including all patients followed for fetal anemia requiring IUT. The indications for MRI were: hydrops fetalis and / or hemoglobin <5 g / dL and / or more than 3 IUTs and / or acute severe anemia and / or ultrasound abnormality. Fetal and neonatal outcome and pediatric neurological monitoring were studied.
89 patients were followed for fetal anemia with IUT and 28 (29.1%) had fetal MRI, 12 of which were abnormal. Two out of twelve had abnormal ultrasound. Seven out of twelve had poor neurological prognosis: 2 medical terminations of pregnancy were performed; 2 children had severe developmental delay and 3 children had schooling difficulties. Five out of twelve children had favorable neurological prognosis.
MRI of the fetal brain makes it possible to better detect brain lesions than ultrasound does in the management of severe fetal anemia and seems particularly appropriate in cases of acute anemia.
Management of pain is one of the major expectations of children with neurological impairment and their families. The medical literature is poor on this topic accounting for approximately 0.15 % of ...the publications on pain in general. The objective of the French Pediatric Neurology Society was to review the current knowledge on this topic. Bibliographic research was conducted with PubMed and RefDoc for publications between 1994 and 2014 in French or English. A total of 925 articles were retrieved and 92 were selected for review. Pain is common in this population: a 2-week survey indicated that pain occurs in 50-75 % of children. Pain negatively impacts the quality of life of children and their parents. Children with neurological impairment express their pain with pain expression patterns and specific patterns common to children (change of tone, abnormal movements, spasticity, paradoxical reactions, such as laughter, self-injury or vasomotor dysfunction). Some children with neurological impairment are able to use self-report pain scales. If not, observational measures should be used. Behavioral rating scales specifically designed for this population are more sensitive than others. Scales must be selected according to children's communication skills, type of pain, and the context. Sometimes behavioral changes are the only expression of pain: any change in sleep, tone, feeding, or mood must suggest pain in this population. Management of pain remains difficult. There are no specific guidelines. Procedural pain management guidelines and the usual analgesic drugs can be used in children with neurological impairment with specific concerns regarding tolerance and side effects. These children are particularly at risk for neuropathic pain. A multidisciplinary approach is helpful, involving physicians, nurses, physiotherapists, psychologists and parents.
We have recently shown that de novo mutations in the TUBA1A gene are responsible for a wide spectrum of neuronal migration disorders. To better define the range of these abnormalities, we searched ...for additional mutations in a cohort of 100 patients with lissencephaly spectrum for whom no mutation was identified in DCX, LIS1 and ARX genes and compared these data to five previously described patients with TUBA1A mutations.
We detected de novo TUBA1A mutations in six patients and highlight the existence of a prominent form of TUBA1A related lissencephaly. In four patients, the mutations identified, c.1190T>C (p.L397P), c.1265G>A (p.R422H), c.1264C>T (p.R422C), c.1306G>T (p.G436R), have not been reported before and in two others, the mutation corresponds to a recurrent missense mutation, c.790C>T (p.R264C), likely to be a hot spot of mutation. All together, it emerges that the TUBA1A related lissencephaly spectrum ranges from perisylvian pachygyria, in the less severe form, to posteriorly predominant pachygyria in the most severe, associated with dysgenesis of the anterior limb of the internal capsule and mild to severe cerebellar hypoplasia. When compared with a large series of lissencephaly of other origins (ILS17, ILSX or unknown origin), these features appear to be specific to TUBA1A related lissencephaly. In addition, TUBA1A mutated patients share a common clinical phenotype that consists of congenital microcephaly, mental retardation and diplegia/tetraplegia.
Our data highlight the presence of consistent and specific abnormalities that should allow the differentiation of TUBA1A related lissencephalies from those related to LIS1, DCX and ARX genes.
In 2005, the French law on patients' rights at the end of life required that decisions to withdraw or withhold life-sustaining treatments be made and carried out by the physician in charge of the ...patient, after obtaining advice from an independent consulting colleague and the caregiving team. The purpose of this study was to identify theoretical and practical obstacles to this collaborative deliberation and to propose practical guidelines to organize it.
In 2005, the French law on patients' rights at the end of life ratified that decisions to withdraw or withhold life-sustaining treatments must be made and carried out by the physician in charge of ...the patient, after obtaining the advice of an independent consulting colleague. The purpose of this text is to put forward the perspective of a pediatric multidisciplinary workshop regarding the role of the consulting physician and to propose guidelines to help choose this consultant.
Characteristics of tuberous sclerosis in children Riquet, A; Cuisset, J-M; Cuvellier, J-C ...
Archives de pédiatrie : organe officiel de la Société française de pédiatrie
17, Številka:
9
Journal Article
Recenzirano
Tuberous sclerosis complex is a genetic multisystem disease characterized by hamartic development of many organs, most notably the brain, heart, kidneys, lungs, and skin. This autosomic dominant ...disorder results from mutations in one of two genes, TSC1 and TSC2, coding for hamartin and tuberin, respectively. The hamartin-tuberin complex inhibits the mammalian target of rapamycin pathway, which controls cell growth and proliferation. The clinical presentation is highly variable and most features of tuberous sclerosis become evident only in childhood after the child is several years of age, limiting their usefulness for early diagnosis. The aim of this article is to define the pediatric clinical manifestations of tuberous sclerosis in correlation with patient age. Sometimes, a prenatal diagnosis can be made based on fetal ultrasound and MRI, which show cardiac and brain lesions. However, newborns are most often asymptomatic. In the 1st year, seizures are the most common symptoms, with a high incidence of infantile spasms. In children between 2 and 10 years of age, neurological symptoms are the most frequent with epilepsy, mental retardation, and autism, but extraneurological manifestations can be diagnosed. In adolescents, most features of tuberous sclerosis become evident and renal and pulmonary manifestations must be sought. The knowledge of age-dependent clinical features of tuberous sclerosis can provide an earlier diagnosis and improve the management of these patients with a special role for multidisciplinary consultation.
La loi du 22 avril 2005 relative aux droits des malades et à la fin de vie (dite « loi Leonetti ») a donné un cadre légal aux décisions de limitation et d’arrêt de traitement (LAT) et a instauré ...l’obligation d’une délibération collégiale pour les patients hors d’état d’exprimer leur volonté. Les modalités de cette collégialité ont été précisées par le décret du 6 février 2006 qui impose au médecin en charge du patient de prendre l’avis motivé d’un consultant avant toute décision de LAT. Ces dispositions qui ont été intégrées dans l’article 37 du Code de déontologie médicale, nécessitent leur appropriation dans des disciplines dont la culture et la temporalité sont très différentes. En pédiatrie, l’application de cette loi doit tenir compte du rôle des parents puisque, sur le plan légal, l’enfant est représenté par ses parents, qu’il soit ou non en état d’exprimer sa volonté. L’objectif de ce texte est de définir les situations requérant la présence d’un consultant au sens de la loi Leonetti en pédiatrie, de préciser son positionnement et son rôle, et de proposer des éléments d’orientation pour en guider le choix en pratique.
In 2005, the French law on patients’ rights at the end of life ratified that decisions to withdraw or withhold life-sustaining treatments must be made and carried out by the physician in charge of the patient, after obtaining the advice of an independent consulting colleague. The purpose of this text is to put forward the perspective of a pediatric multidisciplinary workshop regarding the role of the consulting physician and to propose guidelines to help choose this consultant.
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