Steffen A.,University of Lübeck |
Beutner D.,Klinik und Poliklinik fur HNO Heilkunde |
Hakim S.,University of Lübeck |
Jost W.,Fachbereich Neurologie |
And 14 more authors.
Laryngo- Rhino- Otologie | Year: 2013
Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This reduces social interaction chances and burdens daily care. Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, and saliva aspiration. Therefore, a multidisciplinary S2k guideline was developed. Diagnostic tools such as fiberoptic endoscopic evaluation of swallowing and videofluoroscopic swallowing studies generate important data on therapy selection and control. Especially traumatic and oncologic cases profit from swallowing therapy programmes in order to activate compensation mechanisms. In children with hypotonic oral muscles, oralstimulation plates can induce a relevant symptom release because of the improved lip closure. In acute hypersalivation, the pharmacologic treatment with glycopyrrolate and scopolamine in various applications is useful but its value in long-term usage critical. The injection of botulinum toxin into the salivary glands has shown safe and effective results with long lasting saliva reduction. Surgical treatment should be reserved for isolated cases. External radiation is judged as ultima ratio. Therapy effects and symptom severity has to be followed, especially in neurodegenerative cases. The resulting xerostomia should be critically evaluated by the responsible physician regarding oral and dental hygiene. © Georg Thieme Verlag KG Stuttgart · New York.
Limbrock J.G.,Kinderzentrum Munich
Journal fur Neurologie, Neurochirurgie und Psychiatrie | Year: 2011
Sucking and swallowing problems may already arise in the first year of life in a child with ICP, but mostly the typical oral motor problems develop later: openmouth posture, tongue thrust, drooling, choking on lumpy or solid food, or on liquids (dysphagia), dysarthria etc. This review article highlights the corresponding areas of posture, respiration, lip seal, tongue, mucosa, dental and maxillary position, drinking and eating, and articulation - based on up-todate literature. Drooling has many implications for social participation (International Classification of Functioning [ICF]), and is highlighted with pathogenetic and therapeutic reasoning. Reduction of saliva - by drugs or surgery - does not touch the root of the problem - the effectiveness and frequency of swallowing - and often leads to long-term consequences for teeth, oral hygiene, and swallowing. Therefore, improvement of functions is preferred, and such therapies are discussed. Two are specially depicted: The Castillo Morales® concept, including stimulating palatal plates, and the Pörnbacher therapy (NEPA). They approach whole-body motricity and indirectly and directly also oral motricity and perception. Finally, the indication for gastrostomy feeding is reflected, considering new findings on the neuroplasticity of swallowing.
Juen F.,Kinderzentrum Munich
Praxis der Kinderpsychologie und Kinderpsychiatrie | Year: 2014
Clinical relevance of variations within the ability to mentalize is usually reported in the field of psychopathology in adults. This might be due to difficulties in methods for empirical assessment of this capacity in children. In this short report the author discusses facets and abilities of how to engage the inner world of young children with story stem techniques and especially how to register variations in the ability to mentalize. Ideas for assessment in early childhood are presented and illustrated along two clinical vignettes. This paper gives a short impression of clinical diagnostics of mentalization in childhood. © Vandenhoeck & Ruprecht GmbH & Co. KG, Göttingen 2014.
Sommer A.,University Hospital Freiburg |
Christensen E.,Rigshospitalet |
Schwenger S.,Kinderzentrum Munich |
Seul R.,Marien Hospital Witten |
And 4 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2011
Aminoacylase 1 is a zinc-binding enzyme which hydrolyzes N-acetyl amino acids into the free amino acid and acetic acid. Deficiency of aminoacylase 1 due to mutations in the aminoacylase 1 (ACY1) gene follows an autosomal-recessive trait of inheritance and is characterized by accumulation of N-acetyl amino acids in the urine. In affected individuals neurological findings such as febrile seizures, delay of psychomotor development and moderate mental retardation have been reported. Except for one missense mutation which has been studied in Escherichia coli, mutations underlying aminoacylase 1 deficiency have not been characterized so far. This has prompted us to approach expression studies of all mutations known to occur in aminoacylase 1 deficient individuals in a human cell line (HEK293), thus providing the authentic human machinery for posttranslational modifications. Mutations were inserted using site directed mutagenesis and aminoacylase 1 enzyme activity was assessed in cells overexpressing aminoacylase 1, using mainly the natural high affinity substrate N-acetyl methionine. Overexpression of the wild type enzyme in HEK293 cells resulted in an approximately 50-fold increase of the aminoacylase 1 activity of homogenized cells. Most mutations resulted in a nearly complete loss of enzyme function. Notably, the two newly discovered mutations p.Arg378Trp, p.Arg378Gln and the mutation p.Arg393His yielded considerable residual activity of the enzyme, which is tentatively explained by their intramolecular localization and molecular characteristics. In contrast to aminoacylase 1 variants which showed no detectable aminoacylase 1 activity, aminoacylase 1 proteins with the mutations p.Arg378Trp, p.Arg378Gln and p.Arg393His were also detected in Western blot analysis. Investigations of the molecular bases of additional cases of aminoacylase 1 deficiency contribute to a better understanding of this inborn error of metabolism whose clinical significance and long-term consequences remain to be elucidated. © 2011 Elsevier B.V.
Thummerer Y.,Kinderzentrum Munich |
von Kries R.,Ludwig Maximilians University of Munich |
Marton M.-A.,Kinderzentrum Munich |
Beyerlein A.,Ludwig Maximilians University of Munich
Gait and Posture | Year: 2012
Background: Gait analysis is an increasingly used tool in the evaluation of neurological or orthopaedic problems in children. A good insight into age-related changes in normal paediatric gait is necessary to evaluate gait inefficiency caused by pathological walking patterns in children. However, no systematic evaluation of the normal development of trunk movement has yet been made. Methods: Data of n= 85 healthy children were available. They were asked to walk at self selected speed. The gait data were measured with the Vicon Plug-In-Gait model, including the trunk. We assessed gait cycles of thorax, spine and pelvis in the sagittal, frontal and transverse plane, respectively, stratified by age (categories: <4, 4-6, 7-9, 10-12 and 13-16 years) as well as by normalized speed (≤0.40, 0.41-0.49, ≥0.50). Results: The sagittal thorax and spine movement was found to be gradually and significantly associated with age, but less so with speed, indicating that, with increasing age, children tend to lean their trunk forward relative to both the global co-ordinate system and the pelvis. In contrast, the frontal and transverse parameters of spine and pelvic movement seemed to depend mainly on speed, not age. Conclusion: Our study shows that age dependency has to be considered with respect to sagittal thorax and spine movements. This finding might be of great importance with respect to the identification of pathological patterns in trunk movement. © 2011 Elsevier B.V.
Huang L.,Genetics and Molecular Pathology |
Huang L.,Central South University |
Jolly L.A.,Genetics and Molecular Pathology |
Willis-Owen S.,Genetics and Molecular Pathology |
And 20 more authors.
American Journal of Human Genetics | Year: 2012
The discovery of mutations causing human disease has so far been biased toward protein-coding regions. Having excluded all annotated coding regions, we performed targeted massively parallel resequencing of the nonrepetitive genomic linkage interval at Xq28 of family MRX3. We identified in the binding site of transcription factor YY1 a regulatory mutation that leads to overexpression of the chromatin-associated transcriptional regulator HCFC1. When tested on embryonic murine neural stem cells and embryonic hippocampal neurons, HCFC1 overexpression led to a significant increase of the production of astrocytes and a considerable reduction in neurite growth. Two other nonsynonymous, potentially deleterious changes have been identified by X-exome sequencing in individuals with intellectual disability, implicating HCFC1 in normal brain function. © 2012 The American Society of Human Genetics.
Steenweg M.E.,VU University Amsterdam |
Van Berge L.,VU University Amsterdam |
Van Berkel C.G.M.,VU University Amsterdam |
De Coo I.F.M.,Erasmus Medical Center |
And 12 more authors.
Neuropediatrics | Year: 2012
AimLeukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is known as a relatively mild leukoencephalopathy. We investigated the occurrence of severe variants of LBSL with extensive brain magnetic resonance imaging (MRI) abnormalities. MethodMRIs of approximately 3,000 patients with an unknown leukoencephalopathy were retrospectively reviewed for extensive signal abnormalities of the cerebral and cerebellar white matter, posterior limb of the internal capsule, cerebellar peduncles, pyramids, and medial lemniscus. Clinical data were retrospectively collected. ResultsEleven patients fulfilled the MRI criteria (six males); six had DARS2 mutations. Clinical and laboratory findings did not distinguish between patients with and without DARS2 mutations, but MRI did. Patients with DARS2 mutations more often had involvement of structures typically affected in LBSL, including decussatio of the medial lemniscus, anterior spinocerebellar tracts, and superior and inferior cerebellar peduncles. Also, involvement of the globus pallidus was associated with DARS2 mutations. Earliest disease onset was neonatal; earliest death at 20 months. InterpretationThis study confirms the occurrence of early infantile, severe LBSL, extending the known phenotypic range of LBSL. Abnormality of specific brainstem tracts and cerebellar peduncles are MRI findings that point to the correct diagnosis. Copyright © 2012 by Thieme Medical Publishers, Inc.
Gregor A.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Albrecht B.,University of Duisburg - Essen |
Bader I.,Kinderzentrum Munich |
Bijlsma E.K.,Leiden University |
And 17 more authors.
BMC Medical Genetics | Year: 2011
Background: Heterozygous copy-number and missense variants in CNTNAP2 and NRXN1 have repeatedly been associated with a wide spectrum of neuropsychiatric disorders such as developmental language and autism spectrum disorders, epilepsy and schizophrenia. Recently, homozygous or compound heterozygous defects in either gene were reported as causative for severe intellectual disability.Methods: 99 patients with severe intellectual disability and resemblance to Pitt-Hopkins syndrome and/or suspected recessive inheritance were screened for mutations in CNTNAP2 and NRXN1. Molecular karyotyping was performed in 45 patients. In 8 further patients with variable intellectual disability and heterozygous deletions in either CNTNAP2 or NRXN1, the remaining allele was sequenced.Results: By molecular karyotyping and mutational screening of CNTNAP2 and NRXN1 in a group of severely intellectually disabled patients we identified a heterozygous deletion in NRXN1 in one patient and heterozygous splice-site, frameshift and stop mutations in CNTNAP2 in four patients, respectively. Neither in these patients nor in eight further patients with heterozygous deletions within NRXN1 or CNTNAP2 we could identify a defect on the second allele. One deletion in NRXN1 and one deletion in CNTNAP2 occurred de novo, in another family the deletion was also identified in the mother who had learning difficulties, and in all other tested families one parent was shown to be healthy carrier of the respective deletion or mutation.Conclusions: We report on patients with heterozygous defects in CNTNAP2 or NRXN1 associated with severe intellectual disability, which has only been reported for recessive defects before. These results expand the spectrum of phenotypic severity in patients with heterozygous defects in either gene. The large variability between severely affected patients and mildly affected or asymptomatic carrier parents might suggest the presence of a second hit, not necessarily located in the same gene. © 2011 Gregor et al; licensee BioMed Central Ltd.
PubMed | Kinderzentrum Munich
Type: Journal Article | Journal: Gait & posture | Year: 2012
Gait analysis is an increasingly used tool in the evaluation of neurological or orthopaedic problems in children. A good insight into age-related changes in normal paediatric gait is necessary to evaluate gait inefficiency caused by pathological walking patterns in children. However, no systematic evaluation of the normal development of trunk movement has yet been made.Data of n=85 healthy children were available. They were asked to walk at self selected speed. The gait data were measured with the Vicon Plug-In-Gait model, including the trunk. We assessed gait cycles of thorax, spine and pelvis in the sagittal, frontal and transverse plane, respectively, stratified by age (categories: <4, 4-6, 7-9, 10-12 and 13-16 years) as well as by normalized speed ( 0.40, 0.41-0.49, 0.50).The sagittal thorax and spine movement was found to be gradually and significantly associated with age, but less so with speed, indicating that, with increasing age, children tend to lean their trunk forward relative to both the global co-ordinate system and the pelvis. In contrast, the frontal and transverse parameters of spine and pelvic movement seemed to depend mainly on speed, not age.Our study shows that age dependency has to be considered with respect to sagittal thorax and spine movements. This finding might be of great importance with respect to the identification of pathological patterns in trunk movement.
PubMed | Center for the Biology of Disease, Max Planck Institute for Molecular Genetics, Genetics of Learning and Disability Service, Justus Liebig University and 22 more.
Type: Journal Article | Journal: Molecular psychiatry | Year: 2015
X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.