coffin lowry syndrome

Summary

Summary: A rare, X-linked INTELLECTUAL DISABILITY syndrome that results from mutations in the RIBOSOMAL PROTEIN S6 KINASE gene. Typical manifestations of the disease include an intelligence quotient of less than 50, facial anomalies, and other malformations.

Top Publications

  1. Ahuja S, Upadhye S, Kulkarni H, Kulkarni M. Coffin-Lowry syndrome. Indian J Pediatr. 2003;70:1001-2 pubmed
    ..The authors report a one and half year old boy with classical features of this syndrome. Early recognition of this condition is important for genetic counseling and prevention of progressive skeletal deformities...
  2. Owlia F, Akhavan Karbassi M, Hakimian R, Alemrajabi M. A Highlighted Case for Emphasizing on Clinical Diagnosis for Rare Syndrome in Third World. Iran J Child Neurol. 2017;11:77-80 pubmed
    ..He was diagnosed as Papillon-Lefevre syndrome already, just because of early tooth loss and palmar keratosis...
  3. Cho Y. Molecular Targeting of ERKs/RSK2 Signaling in Cancers. Curr Pharm Des. 2017;23:4247-4258 pubmed publisher
    ..Here, we will extensively discuss signaling pathways regulating RSK2 activity, the role of RSK2 in human cancer development, inhibitors suppressing RSK2 activity, and why RSK2 is an important target to develop drugs for human cancers...
  4. Hirakawa M, Nishihara T, Nakanishi K, Kitamura S, Fujii S, Ikemune K, et al. Perioperative management of a patient with Coffin-Lowry syndrome complicated by severe obesity: A case report and literature review. Medicine (Baltimore). 2017;96:e9026 pubmed publisher
    ..In this case report, we discuss anesthetic and postoperative considerations in patients with CLS, focusing on difficult airway management, and summarize past reports including some Japanese articles...
  5. Stephenson J, Hoffman M, Russell A, Falconer J, Beach R, Tolmie J, et al. The movement disorders of Coffin-Lowry syndrome. Brain Dev. 2005;27:108-13 pubmed
    ..This unique combination of more than one non-epileptic movement disorder and epilepsy deserves further semiological and genetic study both for the patients with CLS and for the wider implications...
  6. Sheffler D, Kroeze W, Garcia B, Deutch A, Hufeisen S, Leahy P, et al. p90 ribosomal S6 kinase 2 exerts a tonic brake on G protein-coupled receptor signaling. Proc Natl Acad Sci U S A. 2006;103:4717-22 pubmed
    ..Because RSK2-inactivating mutations in humans lead to Coffin-Lowry syndrome, our results imply that alterations in GPCR signaling may account for some of its clinical manifestations...
  7. Marques Pereira P, Gruss M, Braun K, Foos N, Pannetier S, Hanauer A. Dopaminergic system dysregulation in the mrsk2_KO mouse, an animal model of the Coffin-Lowry syndrome. J Neurochem. 2008;107:1325-34 pubmed publisher
    ..This cortical hyperdopaminergia may explain some non-cognitive but also cognitive alterations exhibited by mrsk2_KO mice...
  8. Havaligi N, Matadeen Ali C, Khurana D, Marks H, Kothare S. Treatment of drop attacks in Coffin-Lowry syndrome with the use of sodium oxybate. Pediatr Neurol. 2007;37:373-4 pubmed
  9. Micheli V, Sestini S, Parri V, Fichera M, Romano C, Ariani F, et al. RSK2 enzymatic assay as a second level diagnostic tool in Coffin-Lowry syndrome. Clin Chim Acta. 2007;384:35-40 pubmed
    ..In order to exclude that these patients have RSK2 mutations missed by standard mutation detection techniques, a rapid and sensitive assay allowing evaluation of RSK2 activity was needed...

More Information

Publications52

  1. Martin T. Protein nutrition as therapy for a genetic disorder of bone?. Cell Metab. 2006;4:419-20 pubmed
    ..In this issue, , studying the role of the transcription factor ATF4 in a new mouse model of neurofibromatosis type I skeletal defects, demonstrate striking effects of changing dietary protein on bone formation abnormalities...
  2. Field M, Tarpey P, Boyle J, Edkins S, Goodship J, Luo Y, et al. Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation. Clin Genet. 2006;70:509-15 pubmed
    ..These families show that strict reliance on classical clinical criteria for mutation testing may result in a missed diagnosis. A less targeted screening approach to mutation testing is advocated...
  3. Mundkur N. Neuroplasticity in children. Indian J Pediatr. 2005;72:855-7 pubmed
    ..Technological advances in non invasive imaging techniques and advances in molecular genetics have helped us understand the basis of many developmental disorders which may help in planning effective intervention strategies...
  4. Nishino S, Kanbayashi T. Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system. Sleep Med Rev. 2005;9:269-310 pubmed
    ..It appears that further studies of the involvement of the hypocretin system in symptomatic narcolepsy and EDS are helpful to understand the pathophysiological mechanisms for the occurrence of EDS and cataplexy...
  5. Nakamura M, Yamagata T, Mori M, Momoi M. RSK2 gene mutations in Coffin-Lowry syndrome with drop episodes. Brain Dev. 2005;27:114-7 pubmed
    ..All mutations in our patient and those previously reported in patients with drop episodes result in premature truncation of the RSK2 protein in the N-terminal kinase domain or upstream of this domain...
  6. Weeber E, Levenson J, Sweatt J. Molecular genetics of human cognition. Mol Interv. 2002;2:376-91, 339 pubmed
  7. Simensen R, Abidi F, Collins J, Schwartz C, Stevenson R. Cognitive function in Coffin-Lowry syndrome. Clin Genet. 2002;61:299-304 pubmed
    ..Normal females in the family did not demonstrate skewing. The correlation coefficient between IQ and X-inactivation status among carriers was not significant...
  8. Patlas M, Joseph A, Cohen J, Gomori J. MRI and MRS of Coffin-Lowry syndrome: a case report. Neurol Res. 2003;25:285-6 pubmed
    ..There were moderately enlarged lateral and third ventricles and subarachnoid space with prominent Virchow-Robin spaces. MRS of basal ganglia and periventricular white matter was normal...
  9. Nelson G, Hahn J. Stimulus-induced drop episodes in Coffin-Lowry syndrome. Pediatrics. 2003;111:e197-202 pubmed
    ..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...
  10. Fryssira H, Kountoupi S, Delaunoy J, Thomaidis L. A female with Coffin-Lowry syndrome and "cataplexy". Genet Couns. 2002;13:405-9 pubmed
    ..The episodes were precipitated by emotional or auditory stimuli and were significantly reduced, by selective serotonine re-uptake inhibitors...
  11. Poirier R, Jacquot S, Vaillend C, Soutthiphong A, Libbey M, Davis S, et al. Deletion of the Coffin-Lowry syndrome gene Rsk2 in mice is associated with impaired spatial learning and reduced control of exploratory behavior. Behav Genet. 2007;37:31-50 pubmed
    ..The observed behavioral changes are in line with observations made in other mouse models of human mental retardation and support a role of Rsk2 in cognitive functions...
  12. McGaughran J, Delaunoy J. Coffin-Lowry syndrome in a patient from the Cook Islands confirmed by the presence of a unique mutation. Am J Med Genet. 2002;113:309-11 pubmed
  13. Marques Pereira P, Heron D, Hanauer A. The first large duplication of the RSK2 gene identified in a Coffin-Lowry syndrome patient. Hum Genet. 2007;122:541-3 pubmed
  14. Wasersprung D, Sarnat H. Coffin-Lowry syndrome: findings and dental treatment. Spec Care Dentist. 2006;26:220-4 pubmed
    ..Despite difficulties in management, the dental treatment for caries and gingivitis could be completed on the brothers without sedation...
  15. Dugani C, Paquin A, Kaplan D, Miller F. Coffin-Lowry syndrome: a role for RSK2 in mammalian neurogenesis. Dev Biol. 2010;347:348-59 pubmed publisher
  16. Herrera Soto J, Santiago Cornier A, Segal L, Ramirez N, Tamai J. The musculoskeletal manifestations of the Coffin-Lowry syndrome. J Pediatr Orthop. 2007;27:85-9 pubmed
    ..Hypoplasia of the ilium and hand deformities are common but do not seem to cause any functional problems. Observation is recommended for these asymptomatic hand, foot, and pelvic findings...
  17. Zeniou M, Gattoni R, Hanauer A, Stevenin J. Delineation of the mechanisms of aberrant splicing caused by two unusual intronic mutations in the RSK2 gene involved in Coffin-Lowry syndrome. Nucleic Acids Res. 2004;32:1214-23 pubmed
    ..Thus, our results explain how these mutations cause severe forms of CLS...
  18. Zhang Y, Cho Y, Petersen B, Bode A, Zhu F, Dong Z. Ataxia telangiectasia mutated proteins, MAPKs, and RSK2 are involved in the phosphorylation of STAT3. J Biol Chem. 2003;278:12650-9 pubmed
    ..Additionally, RSK2-mediated phosphorylation of STAT3 (Ser(727)) was further determined to be required for basal and UVA-stimulated STAT3 transcriptional activities...
  19. Igari K, Hozumi Y, Monma Y, Mayanagi H. A case of Coffin-Lowry syndrome with premature exfoliation of primary teeth. Int J Paediatr Dent. 2006;16:213-7 pubmed
    ..Premature exfoliation of primary teeth in Coffin-Lowry syndrome has been described in a few reports. This manifestation of the disease would be helpful for diagnosis at an early stage as those previous reports suggested...
  20. Falco M, Romano C, Alberti A, Greco D, Scuderi C, Avola E, et al. Identification of novel mutations in patients with Coffin-Lowry syndrome by a denaturing HPLC-based assay. Clin Chem. 2005;51:2356-8 pubmed
  21. Hunter A. Coffin-Lowry syndrome: a 20-year follow-up and review of long-term outcomes. Am J Med Genet. 2002;111:345-55 pubmed
    ..There are few data on patients over the age of 30, and much more longer term follow-up is required...
  22. Facher J, Regier E, Jacobs G, Siwik E, Delaunoy J, Robin N. Cardiomyopathy in Coffin-Lowry syndrome. Am J Med Genet A. 2004;128A:176-8 pubmed
    ..This is the first description of the histology and electron microscopy of cardiomyopathy in CLS...
  23. Ausio J, Levin D, De Amorim G, Bakker S, MacLeod P. Syndromes of disordered chromatin remodeling. Clin Genet. 2003;64:83-95 pubmed
  24. Pereira P, Schneider A, Pannetier S, Heron D, Hanauer A. Coffin-Lowry syndrome. Eur J Hum Genet. 2010;18:627-33 pubmed publisher
    ..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...
  25. Zeniou M, Ding T, Trivier E, Hanauer A. Expression analysis of RSK gene family members: the RSK2 gene, mutated in Coffin-Lowry syndrome, is prominently expressed in brain structures essential for cognitive function and learning. Hum Mol Genet. 2002;11:2929-40 pubmed
    ..Based on the expression levels, our results suggest that in these areas, the Rsk1 and Rsk3 genes may not be able to fully compensate for a lack of Rsk2 function...
  26. Zeniou Meyer M, Liu Y, Béglé A, Olanich M, Olanish M, Hanauer A, et al. The Coffin-Lowry syndrome-associated protein RSK2 is implicated in calcium-regulated exocytosis through the regulation of PLD1. Proc Natl Acad Sci U S A. 2008;105:8434-9 pubmed publisher
  27. Johnston M. Injury and plasticity in the developing brain. Exp Neurol. 2003;184 Suppl 1:S37-41 pubmed
  28. Kaphzan H, Doron G, Rosenblum K. Co-application of NMDA and dopamine-induced rapid translation of RSK2 in the mature hippocampus. J Neurochem. 2007;103:388-99 pubmed
  29. Chen T, Wang Y, Martinez J, Wilson G, He X, Tuck Muller C, et al. Gene symbol: RPS6KA3. Hum Genet. 2007;121:288 pubmed
  30. Kesler S, Simensen R, Voeller K, Abidi F, Stevenson R, Schwartz C, et al. Altered neurodevelopment associated with mutations of RSK2: a morphometric MRI study of Coffin-Lowry syndrome. Neurogenetics. 2007;8:143-7 pubmed
    ..We provide preliminary evidence that the magnitude of hippocampus volume deviation from that of controls may predict general cognitive outcome in CLS...
  31. Coffin G. Postmortem findings in the Coffin-Lowry Syndrome. Genet Med. 2003;5:187-93 pubmed
    ..2 and demonstrated that it works by influencing the activation of other genes. The "monopolygenic" pattern may help to explain the large number of seemingly unrelated abnormalities that make up this syndrome...
  32. David J, Mehic D, Bakiri L, Schilling A, Mandic V, Priemel M, et al. Essential role of RSK2 in c-Fos-dependent osteosarcoma development. J Clin Invest. 2005;115:664-72 pubmed
    ..Therefore, RSK2-dependent stabilization of c-Fos is essential for osteosarcoma formation in mice and may also be important for human osteosarcomas...
  33. Valdovinos M, Napolitano D, Zarcone J, Hellings J, Williams D, Schroeder S. Multimodal evaluation of risperidone for destructive behavior: functional analysis, direct observations, rating scales, and psychiatric impressions. Exp Clin Psychopharmacol. 2002;10:268-75 pubmed
    ..Results indicate that risperidone does decrease destructive behavior and that, for the most part, all of the various measures yielded similar results...
  34. Delaunoy J, Dubos A, Marques Pereira P, Hanauer A. Identification of novel mutations in the RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome. Clin Genet. 2006;70:161-6 pubmed
    ..This study further confirms the high rate of new mutations at the RSK2 locus. It is important to consider the possibility of mosaicism when providing genetic counseling in CLS families...
  35. Wang Y, Martinez J, Wilson G, He X, Tuck Muller C, Maertens P, et al. A novel RSK2 (RPS6KA3) gene mutation associated with abnormal brain MRI findings in a family with Coffin-Lowry syndrome. Am J Med Genet A. 2006;140:1274-9 pubmed
    ..The pathological function of the mutation and genotype/phenotype correlation between the mutation and this unusual clinical presentation await further clarification...
  36. Lange I, Stone P, Aftimos S. The Coffin-Lowry syndrome: a case report and review of the literature. J Obstet Gynaecol Can. 2010;32:691-4 pubmed
    ..Prenatal ultrasound has afforded insights into many structural and syndromic fetal disorders. In this report, the ultrasound findings were of assistance when counselling a patient who presented with a history of Coffin-Lowry syndrome (CLS)...
  37. Elefteriou F, Benson M, Sowa H, Starbuck M, Liu X, Ron D, et al. ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae. Cell Metab. 2006;4:441-51 pubmed
    ..By showing that ATF4-dependent skeletal dysplasiae are treatable by dietary manipulations, this study reveals a molecular connection between nutrition and skeletal development...
  38. Zeniou Meyer M, Béglé A, Bader M, Vitale N. The Coffin-Lowry syndrome-associated protein RSK2 controls neuroendocrine secretion through the regulation of phospholipase D1 at the exocytotic sites. Ann N Y Acad Sci. 2009;1152:201-8 pubmed publisher
    ..Expression of PLD1 phosphomimetic mutants fully restores secretion in cells depleted of RSK2, suggesting that RSK2 is a critical upstream signaling element in the activation of PLD1 to produce the lipids required for exocytosis...
  39. Lopez Jimenez J, Giménez Prats M. Coffin-Lowry syndrome: odontologic characteristics. Review of the literature and presentation of a clinical case. Med Oral. 2003;8:51-6 pubmed
    ..A description is made of the general and odontologic characteristics of Coffin-Lowry syndrome, with a review of the literature and the report of a clinical case...
  40. Hetzer C, Bisgrove D, Cohen M, Pedal A, Kaehlcke K, Speyerer A, et al. Recruitment and activation of RSK2 by HIV-1 Tat. PLoS ONE. 2007;2:e151 pubmed
    ..Our data identify a novel reciprocal regulation of Tat and RSK2 function, which might serve to induce early changes in the chromatin organization of the HIV LTR...
  41. Touraine R, Zeniou M, Hanauer A. A syndromic form of X-linked mental retardation: the Coffin-Lowry syndrome. Eur J Pediatr. 2002;161:179-87 pubmed
    ..Some missense mutations are associated with milder phenotypes. In one family, a missense mutation was associated solely with mild mental retardation and no other clinical feature...
  42. O Riordan S, Patton M, Schon F. Treatment of drop episodes in Coffin-Lowry syndrome. J Neurol. 2006;253:109-10 pubmed
  43. Martinez Garay I, Ballesta M, Oltra S, Orellana C, Palomeque A, Molto M, et al. Intronic L1 insertion and F268S, novel mutations in RPS6KA3 (RSK2) causing Coffin-Lowry syndrome. Clin Genet. 2003;64:491-6 pubmed