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André Hanauer - One of the best experts on this subject based on the ideXlab platform.

  • identification of the first deep intronic mutation in the rps6ka3 gene in a patient with a severe form of Coffin Lowry Syndrome
    European Journal of Medical Genetics, 2013
    Co-Authors: Anne Schneider, Saskia M Maas, Raoul C M Hennekam, André Hanauer
    Abstract:

    Abstract Coffin–Lowry Syndrome (CLS) is an X-linked disorder characterized by growth and psychomotor retardation, hypotonia and progressive skeletal changes. RPS6KA3 is the only gene known to be associated with CLS, and over 150 distinct inactivating mutations in this gene have so far been reported in CLS patients. However, no defect is found in about half of the CLS compatible patients by exon sequencing. We report here the first deep intronic mutation in RPS6KA3, which is associated with the retention of intronic sequences in the mRNAs. Indeed, this finding suggests that all the patients with a highly suggestive CLS clinical diagnosis, but in whom exon screening has failed to detect a mutation, should be reanalyzed at the RNA level.

  • stimulus induced drop episodes in Coffin Lowry Syndrome
    European Journal of Medical Genetics, 2012
    Co-Authors: Jin S. Hahn, André Hanauer
    Abstract:

    The Coffin-Lowry Syndrome (CLS) is a rare but well-defined X-linked semidominant Syndrome characterized by psychomotor and growth retardation, and progressive skeletal changes. CLS is caused by loss of function mutations in the Rps6ka3 gene encoding the ribosomal S6 kinase 2 (RSK2) protein. A distinctive paroxysmal disorder has been described in some CLS patients, characterized by episodes of sudden falling, without apparent alteration of consciousness, usually induced by unexpected tactile or auditory stimuli. Duration of episodes is very short, usually lasting a few seconds. The appellation "Stimulus-induced drop episodes" (SIDEs) was proposed for these non-epileptic events in CLS patients. SIDEs are clinically heterogeneous; with some patients exhibiting cataplexy-like events characterized by sudden hypotonia and collapse, and others hyperekplexia-like episodes with a startle response. The pathophysiology of SIDEs is not well understood.

  • altered erk mapk signaling in the hippocampus of the mrsk2_ko mouse model of Coffin Lowry Syndrome
    Journal of Neurochemistry, 2011
    Co-Authors: Anne Schneider, Solange Pannetier, Tahir Mehmood, André Hanauer
    Abstract:

    J. Neurochem. (2011) 119, 447–459. Abstract Coffin–Lowry Syndrome is a syndromic form of mental retardation caused by mutations of the Rps6ka3 gene encoding ribosomal s6 kinase (RSK)2. RSK2 belongs to a family containing four members in mammals: RSK1–4. RSKs are serine/threonine kinases and cytosolic substrates of extracellular signal-regulated kinase (ERK) in the Ras/MAPK signaling pathway. RSK2 is highly expressed in the hippocampus, and mrsk2_KO mice display spatial learning and memory impairment. In the present study, we provide evidence of abnormally increased phosphorylation of ERK1/2 in the hippocampus of mrsk2_KO mice. Further studies based on cultured hippocampal neurons revealed that glutamate activates ERK1/2 and RSKs, and confirmed a stronger activation of ERK1/2 in mrsk2_KO neurons than in WT cells. We, thus, provide further evidence that RSK2 exerts a feedback inhibitory effect on the ERK1/2 pathway. We also observed a transient sequestration of P-ERK1/2 in the cytoplasm upon glutamate stimulation. In addition, the transcription factors cAMP response element binding and Ets LiKe gene1 show over-activation in RSK2-deficient neurons. Finally, c-Fos, Zif268 and Arc were significantly over-expressed in mrsk2_KO neurons upon glutamate stimulation. Importantly, the increased phosphorylation of other RSK family members observed in mutant neurons was unable to compensate for RSK2 deficiency. This aberrant ERK1/2 signaling can influence various neuronal functions, and thus play a significant role in cognitive dysfunction in mrsk2_KO mice and in the Coffin-Lowry Syndrome.

  • Coffin Lowry Syndrome
    European Journal of Human Genetics, 2010
    Co-Authors: Patricia Marques Pereira, Solange Pannetier, Anne Schneider, Delphine Heron, André Hanauer
    Abstract:

    Coffin–Lowry Syndrome (CLS) is a syndromic form of X-linked mental retardation, which is characterized in male patients by psychomotor and growth retardation and various skeletal anomalies. Typical facial changes and specific clinical and radiological signs in the hand are useful aids in the diagnosis. CLS is caused by mutations in the RPS6KA3 gene located at Xp22.2, which encodes RSK2, a growth-factor-regulated protein kinase. RPS6KA3 mutations are extremely heterogeneous and lead to loss of phosphotransferase activity in the RSK2 kinase, most often because of premature termination of translation.

  • Coffin Lowry Syndrome
    eLS, 2009
    Co-Authors: André Hanauer
    Abstract:

    The Coffin–Lowry Syndrome (CLS) is a rare but well-defined X-linked semidominant Syndrome. Cardinal features include severe mental retardation, a characteristic facial appearance, digital tapering, short stature and progressive spinal deformity. However, the clinical presentation may be markedly variable both in severity and in the expression of uncommonly associated features. In addition, a few atypical cases of the disease have been reported. Highly heterogeneous loss of function mutations in the RPS6KA3 gene encoding the protein kinase RSK2 are responsible for CLS. About two-thirds of the mutations arise de novo. RSK2 is a member of the ribosomal S6 serine/threonine kinase family, which plays a key role in the Ras-ERK signalling pathway. RSKs are activated by phosphorylation in response to growth factors and neurotransmitters. RSK2 substrates include transcription factors, in accordance with a major role in regulation of gene expression. RSK2 is involved in proliferation, apoptosis and in learning and memory processes. Key concepts Coffin–Lowry Syndrome is an X-linked semidominant Syndrome characterized typically by severe psychomotor and growth retardation, facial dysmorphism, digit abnormalities and progressive skeletal deformations. The estimated incidence is 1 50 000–1 100 000 and approximately 70–80% of patients are sporadic cases. There is no specific treatment. Highly heterogeneous loss-of-function mutations in the RPS6KA3 gene, encoding RSK2, are responsible for Coffin–Lowry Syndrome. Two-thirds of cases arise from new mutations. There is no consistent phenotype/genotype correlation. RSK2 is a serine/threonine kinase that acts at the distal end of the Ras-ERK pathway and is activated by phosphorylation in response to growth factors and neurotransmitters. Mice models for CLS have been generated that exhibit delayed bone formation as well as learning and memory deficits. Keywords: X-linked; RPS6KA3 gene; mental retardation; Coffin–Lowry Syndrome; RSK2

Solange Pannetier - One of the best experts on this subject based on the ideXlab platform.

  • altered erk mapk signaling in the hippocampus of the mrsk2_ko mouse model of Coffin Lowry Syndrome
    Journal of Neurochemistry, 2011
    Co-Authors: Anne Schneider, Solange Pannetier, Tahir Mehmood, André Hanauer
    Abstract:

    J. Neurochem. (2011) 119, 447–459. Abstract Coffin–Lowry Syndrome is a syndromic form of mental retardation caused by mutations of the Rps6ka3 gene encoding ribosomal s6 kinase (RSK)2. RSK2 belongs to a family containing four members in mammals: RSK1–4. RSKs are serine/threonine kinases and cytosolic substrates of extracellular signal-regulated kinase (ERK) in the Ras/MAPK signaling pathway. RSK2 is highly expressed in the hippocampus, and mrsk2_KO mice display spatial learning and memory impairment. In the present study, we provide evidence of abnormally increased phosphorylation of ERK1/2 in the hippocampus of mrsk2_KO mice. Further studies based on cultured hippocampal neurons revealed that glutamate activates ERK1/2 and RSKs, and confirmed a stronger activation of ERK1/2 in mrsk2_KO neurons than in WT cells. We, thus, provide further evidence that RSK2 exerts a feedback inhibitory effect on the ERK1/2 pathway. We also observed a transient sequestration of P-ERK1/2 in the cytoplasm upon glutamate stimulation. In addition, the transcription factors cAMP response element binding and Ets LiKe gene1 show over-activation in RSK2-deficient neurons. Finally, c-Fos, Zif268 and Arc were significantly over-expressed in mrsk2_KO neurons upon glutamate stimulation. Importantly, the increased phosphorylation of other RSK family members observed in mutant neurons was unable to compensate for RSK2 deficiency. This aberrant ERK1/2 signaling can influence various neuronal functions, and thus play a significant role in cognitive dysfunction in mrsk2_KO mice and in the Coffin-Lowry Syndrome.

  • transcriptome profile reveals ampa receptor dysfunction in the hippocampus of the rsk2 knockout mice an animal model of Coffin Lowry Syndrome
    Human Genetics, 2011
    Co-Authors: Solange Pannetier, Patricia Marques Pereira, Anne Schneider, Tahir Mehmood, Mohamedraafet Ammar, Jeremie Sibille, Doulaye Dembele, Christelle Thibaultcarpentier, Nathalie Rouach
    Abstract:

    Coffin–Lowry Syndrome (CLS) is a syndromic form of mental retardation caused by loss of function mutations in the X-linked RPS6KA3 gene, which encodes RSK2, a serine/threonine kinase acting in the MAPK/ERK pathway. The mouse invalidated for the Rps6ka3 (Rsk2-KO) gene displays learning and long-term spatial memory deficits. In the current study, we compared hippocampal gene expression profiles from Rsk2-KO and normal littermate mice to identify changes in molecular pathways. Differential expression was observed for 100 genes encoding proteins acting in various biological pathways, including cell growth and proliferation, cell death and higher brain function. The twofold up-regulated gene (Gria2) was of particular interest because it encodes the subunit GLUR2 of the AMPA glutamate receptor. AMPA receptors mediate most fast excitatory synaptic transmission in the central nervous system. We provide evidence that in the hippocampus of Rsk2-KO mice, expression of GLUR2 at the mRNA and at the protein levels is significantly increased, whereas basal AMPA receptor-mediated transmission in the hippocampus of Rsk2-KO mice is significantly decreased. This is the first time that such deregulations have been demonstrated in the mouse model of the Coffin–Lowry Syndrome. Our findings suggest that a defect in AMPA neurotransmission and plasticity contribute to mental retardation in CLS patients.

  • Coffin Lowry Syndrome
    European Journal of Human Genetics, 2010
    Co-Authors: Patricia Marques Pereira, Solange Pannetier, Anne Schneider, Delphine Heron, André Hanauer
    Abstract:

    Coffin–Lowry Syndrome (CLS) is a syndromic form of X-linked mental retardation, which is characterized in male patients by psychomotor and growth retardation and various skeletal anomalies. Typical facial changes and specific clinical and radiological signs in the hand are useful aids in the diagnosis. CLS is caused by mutations in the RPS6KA3 gene located at Xp22.2, which encodes RSK2, a growth-factor-regulated protein kinase. RPS6KA3 mutations are extremely heterogeneous and lead to loss of phosphotransferase activity in the RSK2 kinase, most often because of premature termination of translation.

  • Dopaminergic system dysregulation in the mrsk2_KO mouse, an animal model of the Coffin-Lowry Syndrome.
    Journal of Neurochemistry, 2008
    Co-Authors: Patricia Marques Pereira, Solange Pannetier, Michael Gruss, Katharina Braun, Nicolas Foos, André Hanauer
    Abstract:

    The Coffin-Lowry Syndrome, a rare syndromic form of X-linked mental retardation, is caused by loss-of-function mutations in the hRSK2 (RPS6KA3) gene. To further investigate RSK2 (90-kDa ribosomal S6 kinase) implication in cognitive processes, a mrsk2_KO mouse has previously been generated as an animal model of Coffin-Lowry Syndrome. The aim of the present study was to identify possible neurochemical dysregulation associated with the behavioral and morphological abnormalities exhibited by mrsk2_KO mice. A cortical dopamine level increase was found in mrsk2_KO mice that was accompanied by an over-expression of dopamine receptor of type 2 and the dopamine transporter. We also detected an increase of total and phosphorylated extracellular regulated kinase that may be responsible for the increased level of tyrosine hydroxylase phosphorylation also observed. By taking into consideration previously reported data, our results strongly suggest that the dopaminergic dysregulation in mrsk2_KO mice may be caused, at least in part, by tyrosine hydroxylase hyperactivity. This cortical hyperdopaminergia may explain some non-cognitive but also cognitive alterations exhibited by mrsk2_KO mice.

  • mutations in the x linked rsk2 gene rps6ka3 in patients with Coffin Lowry Syndrome
    Human Mutation, 2001
    Co-Authors: Jeanpierre Delaunoy, Sylvie Jacquot, Karine Merienne, Solange Pannetier, Fatima Abidi, Maria Zeniou, Michele Schmitt, Charles E Schwartz, André Hanauer
    Abstract:

    RSK2 is a growth factor-regulated serine-threonine protein kinase, acting in the Ras-Mitogen-Activated Protein Kinase (MAPK) signaling pathway. Mutations in the RSK2 gene (RPS6KA3) on chromosome Xp22.2, have been found to cause Coffin-Lowry Syndrome (CLS), an X-linked disorder characterized by psychomotor retardation, characteristic facial and digital abnormalities, and progressive skeletal deformations. By screening of 250 patients with clinical features suggestive of Coffin-Lowry Syndrome, 71 distinct disease-associated RSK2 mutations have been identified in 86 unrelated families. Thirty-eight percent of mutations are missense mutations, 20% are nonsense mutations, 18% are splicing errors, and 21% are short deletion or insertion events. About 57% of mutations result in premature translation termination, and the vast majority are predicted to cause loss of function of the mutant allele. These changes are distributed throughout the RSK2 gene and show no obvious clustering or phenotypic association. However, some missense mutations are associated with milder phenotypes. In one family, one such mutation was associated solely with mild mental retardation. It is noteworthy that nine mutations were found in female probands, with no affected male relatives, ascertained through learning disability and mild but suggestive facial and digital dysmorphisms. Hum Mutat 17:103–116, 2001. © 2001 Wiley-Liss, Inc.

Sylvie Jacquot - One of the best experts on this subject based on the ideXlab platform.

  • atf4 is a substrate of rsk2 and an essential regulator of osteoblast biology implication for Coffin Lowry Syndrome
    Cell, 2004
    Co-Authors: Xiangli Yang, Sylvie Jacquot, Paolo Sassonecorsi, Thorsten Schinke, Koichi Matsuda, Peter Bialek, Howard C Masuoka, Lingzhen Li, Stefano Brancorsini, Tim M Townes
    Abstract:

    Coffin-Lowry Syndrome (CLS) is an X-linked mental retardation condition associated with skeletal abnormalities. The gene mutated in CLS, RSK2, encodes a growth factor-regulated kinase. However, the cellular and molecular bases of the skeletal abnormalities associated with CLS remain unknown. Here, we show that RSK2 is required for osteoblast differentiation and function. We identify the transcription factor ATF4 as a critical substrate of RSK2 that is required for the timely onset of osteoblast differentiation, for terminal differentiation of osteoblasts, and for osteoblast-specific gene expression. Additionally, RSK2 and ATF4 posttranscriptionally regulate the synthesis of Type I collagen, the main constituent of the bone matrix. Accordingly, Atf4-deficiency results in delayed bone formation during embryonic development and low bone mass throughout postnatal life. These findings identify ATF4 as a critical regulator of osteoblast differentiation and function, and indicate that lack of ATF4 phosphorylation by RSK2 may contribute to the skeletal phenotype of CLS.

  • X-linked Coffin-Lowry Syndrome (CLS, MIM 303600, RPS6KA3 gene, protein product known under various names: pp90^rsk2, RSK2, ISPK, MAPKAP1)
    European Journal of Human Genetics, 2002
    Co-Authors: Sylvie Jacquot, Maria Zeniou, Renaud Touraine, André Hanauer
    Abstract:

    The Coffin-Lowry Syndrome (CLS) is a syndromic form of X-linked mental retardation characterised in male patients by psychomotor and growth retardation, and various skeletal anomalies. CLS is caused by mutations in a gene located in Xp22.2 and encoding RSK2, a growth-factor regulated protein kinase. Mutations are extremely heterogeneous and lead to premature termination of translation and/or to loss of phosphotransferase activity. No correlation between the type and location of mutation and the clinical phenotype is evident. However, in one family (MRX19), a missense mutation was associated solely with mild mental retardation and no other clinical feature. Screening for RSK2 mutations is essential in most cases to confirm the diagnosis as well as for genetic counseling.

  • mutations in the x linked rsk2 gene rps6ka3 in patients with Coffin Lowry Syndrome
    Human Mutation, 2001
    Co-Authors: Jeanpierre Delaunoy, Sylvie Jacquot, Karine Merienne, Solange Pannetier, Fatima Abidi, Maria Zeniou, Michele Schmitt, Charles E Schwartz, André Hanauer
    Abstract:

    RSK2 is a growth factor-regulated serine-threonine protein kinase, acting in the Ras-Mitogen-Activated Protein Kinase (MAPK) signaling pathway. Mutations in the RSK2 gene (RPS6KA3) on chromosome Xp22.2, have been found to cause Coffin-Lowry Syndrome (CLS), an X-linked disorder characterized by psychomotor retardation, characteristic facial and digital abnormalities, and progressive skeletal deformations. By screening of 250 patients with clinical features suggestive of Coffin-Lowry Syndrome, 71 distinct disease-associated RSK2 mutations have been identified in 86 unrelated families. Thirty-eight percent of mutations are missense mutations, 20% are nonsense mutations, 18% are splicing errors, and 21% are short deletion or insertion events. About 57% of mutations result in premature translation termination, and the vast majority are predicted to cause loss of function of the mutant allele. These changes are distributed throughout the RSK2 gene and show no obvious clustering or phenotypic association. However, some missense mutations are associated with milder phenotypes. In one family, one such mutation was associated solely with mild mental retardation. It is noteworthy that nine mutations were found in female probands, with no affected male relatives, ascertained through learning disability and mild but suggestive facial and digital dysmorphisms. Hum Mutat 17:103–116, 2001. © 2001 Wiley-Liss, Inc.

  • novel mutations in rsk 2 the gene for Coffin Lowry Syndrome cls
    European Journal of Human Genetics, 1999
    Co-Authors: Fatima Abidi, Sylvie Jacquot, André Hanauer, Elisabeth Trivier, Christopher Lassiter, Charles E Schwartz
    Abstract:

    Coffin-Lowry Syndrome (CLS) is an X-linked disorder characterized by facial dysmorphism, digit abnormalities and severe psychomotor retardation. CLS had previously been mapped to Xp22.2. Recently, mutations in the ribosomal S6 kinase (Rsk-2) gene were shown to be associated with CLS. We have tested five unrelated individuals with CLS for mutations in nine exons of Rsk-2 using Single Strand Conformation Polymorphism (SSCP) analysis. Two patients had the same missense mutation (C340T), which causes an arginine to tryptophan change (R114W). This mutation falls just outside the N-terminal ATP-binding site in a highly conserved region of the protein and may lead to structural changes since tryptophan has an aromatic side chain whereas arginine is a 5 carbon basic amino acid. The third patient also had a missense mutation (G2186A) resulting in an arginine to glutamine change (R729Q). The fourth patient had a 2 bp deletion (AG) of bases 451 and 452. This creates a frameshift that results in a stop codon 25 amino acids downstream, thereby producing a truncated protein. This deletion also falls within the highly conserved amino-catalytic domain of the protein. The fifth patient has a nonsense mutation (C2065T) which results in a premature stop codon, thereby producing a truncated protein. These mutations further confirm Rsk-2 as the gene involved in CLS and may help in understanding the structure and function of the protein.

  • Germline mosaicism in Coffin-Lowry Syndrome
    European Journal of Human Genetics, 1998
    Co-Authors: Sylvie Jacquot, Karine Merienne, Solange Pannetier, Sandra Blumenfeld, Albert Schinzel, André Hanauer
    Abstract:

    We have identified a Coffin-Lowry Syndrome pedigree where the disorder is associated with a novel splice site mutation in the RSK2 gene, leading to in-phase skipping of exon 5. Western blot analysis, using an antibody directed against the C-terminus of RSK2, failed to reveal RSK2 in this patient, suggesting strongly that the resulting internally deleted protein is unstable. The mutation was present in the DNA of one affected son and one manifesting daughter but was absent in two asymptomatic daughters, who carry the at-risk haplotype, and in the mother's somatic cell (lymphocyte) DNA. The results are consistent with the mutation arising as a postzygotic event in the mother, who therefore is a germinal mosaic. The application of linked markers to identify the disease allele for conventional genetic counselling would have been misleading in this family. This observation again highlights the importance of precise identification of the disease-causing mutation.

Nathaniel H Robin - One of the best experts on this subject based on the ideXlab platform.

  • foramen magnum compression in Coffin Lowry Syndrome a case report
    American Journal of Medical Genetics Part A, 2017
    Co-Authors: Jariya Upadia, Jerry Oakes, Austin Hamm, Anna C E Hurst, Nathaniel H Robin
    Abstract:

    Coffin-Lowry Syndrome (CLS) is a rare genetic disorder inherited in an X-linked dominant pattern. Common manifestations include intellectual disability, growth retardation, dysmorphic facial features, and variable skeletal anomalies. Here we report a patient who first presented with episodes of apparent life-threatening events (ALTE) found to be caused by hydrocephalus and brainstem compression at the foramen magnum. Together with his small size, short limbs and fingers, and facial appearance, the narrowing of the foramen magnum lead to the initial clinical misdiagnosis of hypochondroplasia. Subsequent evaluation and testing lead to the correct diagnosis of CLS. This case demonstrates the variability in presentation of CLS, and that skeletal findings may be misleading in infancy. © 2017 Wiley Periodicals, Inc.

  • American Journal of Medical Genetics 128A:176–178 (2004) Clinical Report Cardiomyopathy in Coffin–Lowry Syndrome
    2015
    Co-Authors: Nathaniel H Robin
    Abstract:

    Coffin–Lowry Syndrome (CLS) is a rare but well-documented X-linked disorder characterized by small size, developmental delay/mental retarda-tion, and characteristic facial and skeletal find-ings in affected males. The phenotype in affected females is far more variable and can include developmental differences, obesity, and charac-teristic facial and skeletal differences. Cardiac anomalies are reported in less than 20 % of affected males, with cardiomyopathy being one of the rare but reported complications of this disorder. How-ever, cardiomyopathy is not well characterized in CLS. Here, we report on a 14-year-old boy with physical and developmental findings consistent with CLS who presented with a relatively sudden onset of signs of congestive heart failure due to a restrictive cardiomyopathy; an endomyocardial biopsy demonstrated non-specific hypertrophic myocyte alterations consistent with cardiomyo-pathy. This is the first description of the histology and electron microscopy of cardiomyopathy i

  • classic phenotype of Coffin Lowry Syndrome in a female with stimulus induced drop episodes and a genotype with preserved n terminal kinase domain
    American Journal of Medical Genetics Part A, 2014
    Co-Authors: Kitiwan Rojnueangnit, Julie R Jones, Monica J Basehore, Nathaniel H Robin
    Abstract:

    An adolescent female presented with intellectual disability, stimulus-induced drop episodes (SIDEs), facial characteristics that include wide set eyes, short nose with wide columella, full and everted lips with wide mouth and progressive skeletal changes: scoliosis, spondylolisthesis and pectus excavatum. These findings were suggestive of Coffin-Lowry Syndrome (CLS), and this was confirmed by the identification of a novel mutation in RPS6KA3, a heterozygous one basepair duplication at nucleotide 1570 (c.1570dupA). This mutation occurs within the C-terminal kinase domain of the protein, and, therefore contradicts the previous report that SIDEs is only associated with premature truncation of the protein in the N-terminal kinase domain or upstream of this domain. As CLS is X-linked, it is unusual for a female to have such a classic phenotype.

  • cardiomyopathy in Coffin Lowry Syndrome
    American Journal of Medical Genetics Part A, 2004
    Co-Authors: Jennifer J Facher, J P Delaunoy, Elizabeth J Regier, Gretta Jacobs, Ernest Siwik, Nathaniel H Robin
    Abstract:

    Coffin-Lowry Syndrome (CLS) is a rare but well-documented X-linked disorder characterized by small size, developmental delay/mental retardation, and characteristic facial and skeletal findings in affected males. The phenotype in affected females is far more variable and can include developmental differences, obesity, and characteristic facial and skeletal differences. Cardiac anomalies are reported in less than 20% of affected males, with cardiomyopathy being one of the rare but reported complications of this disorder. However, cardiomyopathy is not well characterized in CLS. Here, we report on a 14-year-old boy with physical and developmental findings consistent with CLS who presented with a relatively sudden onset of signs of congestive heart failure due to a restrictive cardiomyopathy; an endomyocardial biopsy demonstrated non-specific hypertrophic myocyte alterations consistent with cardiomyopathy. This is the first description of the histology and electron microscopy of cardiomyopathy in CLS.

  • clinical report cardiomyopathy in Coffin Lowry Syndrome
    2004
    Co-Authors: Jennifer J Facher, J P Delaunoy, Elizabeth J Regier, Gretta Jacobs, Ernest Siwik, Nathaniel H Robin
    Abstract:

    Coffin–Lowry Syndrome (CLS) is a rare but welldocumented X-linked disorder characterized by small size, developmental delay/mental retardation, and characteristic facial and skeletal findings in affected males. The phenotype in affected females is far more variable and can include developmental differences, obesity, and characteristic facial and skeletal differences. Cardiac anomalies are reported in less than 20% of affected males, with cardiomyopathy being one of the rare but reported complications of this disorder. However, cardiomyopathy is not well characterized in CLS. Here, we report on a 14-year-old boy with physical and developmental findings consistent with CLS who presented with a relatively sudden onset of signs of congestive heart failure due to a restrictive cardiomyopathy; an endomyocardial biopsy demonstrated non-specific hypertrophic myocyte alterations consistent with cardiomyopathy. This is the first description of the histology and electron microscopy of cardiomyopathy in

Jin S. Hahn - One of the best experts on this subject based on the ideXlab platform.

  • stimulus induced drop episodes in Coffin Lowry Syndrome
    European Journal of Medical Genetics, 2012
    Co-Authors: Jin S. Hahn, André Hanauer
    Abstract:

    The Coffin-Lowry Syndrome (CLS) is a rare but well-defined X-linked semidominant Syndrome characterized by psychomotor and growth retardation, and progressive skeletal changes. CLS is caused by loss of function mutations in the Rps6ka3 gene encoding the ribosomal S6 kinase 2 (RSK2) protein. A distinctive paroxysmal disorder has been described in some CLS patients, characterized by episodes of sudden falling, without apparent alteration of consciousness, usually induced by unexpected tactile or auditory stimuli. Duration of episodes is very short, usually lasting a few seconds. The appellation "Stimulus-induced drop episodes" (SIDEs) was proposed for these non-epileptic events in CLS patients. SIDEs are clinically heterogeneous; with some patients exhibiting cataplexy-like events characterized by sudden hypotonia and collapse, and others hyperekplexia-like episodes with a startle response. The pathophysiology of SIDEs is not well understood.

  • Stimulus-induced drop episodes in Coffin-Lowry Syndrome
    Pediatrics, 2003
    Co-Authors: Gregg B. Nelson, Jin S. Hahn
    Abstract:

    Objective. Coffin-Lowry Syndrome (CLS) is a rare disorder characterized by moderate to severe mental retardation, facial dysmorphism, tapering digits, and skeletal deformity. Paroxysmal drop attacks occur in patients with CLS, characterized by sudden loss of muscle tone induced by unexpected tactile or auditory stimuli. Our objective is to characterize these attacks better using neurophysiologic studies. Methods. We report 2 teenage boys with CLS and stimulus-induced drop episodes (SIDEs). Simultaneous surface electromyogram (EMG) and video electroencephalogram were performed during SIDEs on our 2 patients. Results. Both patients had SIDEs stimulated by a loud noise, unexpected light touch stimulation, or visual threat that were characterized by abrupt episodes of complete or partial loss of lower extremity tone. These events were not associated with impairment of consciousness, and immediate recovery was noted. Simultaneous surface EMG and video electroencephalogram revealed no epileptiform discharges in either patient. In the first patient, after unexpected tactile or auditory stimulation, tonic EMG activity in paraspinal muscles was lost briefly, similar to that seen in cataplexy. In the second patient, at 6 years of age, sudden nonepileptic drop episodes were induced by an unexpected tactile, auditory, or visual stimulation. At 11 years of age, his episodes had changed to brief myoclonic jerk and tonic spasm that were triggered by unexpected tactile and auditory stimuli. An increase in tonic EMG activity occurred during the attacks, consistent with hyperekplexia. Conclusions. Our data suggest that SIDEs in CLS are a heterogeneous group of nonepileptic events that may manifest features of both cataplexy and hyperekplexia, even in the same patient.