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Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring / A. KOLEVZON in Journal of Neurodevelopmental Disorders, 6-1 (December 2014)
[article]
Titre : Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring Type de document : Texte imprimé et/ou numérique Auteurs : A. KOLEVZON, Auteur ; Benjamin ANGARITA, Auteur ; L. BUSH, Auteur ; A. Ting WANG, Auteur ; Y. FRANK, Auteur ; A. YANG, Auteur ; R. RAPAPORT, Auteur ; J. SALAND, Auteur ; S. SRIVASTAVA, Auteur ; C. FARRELL, Auteur ; L. J. EDELMANN, Auteur ; Joseph D. BUXBAUM, Auteur Article en page(s) : p.39 Langues : Anglais (eng) Mots-clés : 22q13 deletion syndrome Autism Autism spectrum disorder Neurodevelopmental disorders Phelan-McDermid syndrome Practice parameters Shank3 Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) and intellectual disability (ID) can be caused by mutations in a large number of genes. One example is SHANK3 on the terminal end of chromosome 22q. Loss of one functional copy of SHANK3 results in 22q13 deletion syndrome or Phelan-McDermid syndrome (PMS) and causes a monogenic form of ASD and/or ID with a frequency of 0.5% to 2% of cases. SHANK3 is the critical gene in this syndrome, and its loss results in disruption of synaptic function. With chromosomal microarray analyses now a standard of care in the assessment of ASD and developmental delay, and with the emergence of whole exome and whole genome sequencing in this context, identification of PMS in routine clinical settings will increase significantly. However, PMS remains a rare disorder, and the majority of physicians have never seen a case. While there is agreement about core deficits of PMS, there have been no established parameters to guide evaluation and medical monitoring of the syndrome. Evaluations must include a thorough history and physical and dysmorphology examination. Neurological deficits, including the presence of seizures and structural brain abnormalities should be assessed as well as motor deficits. Endocrine, renal, cardiac, and gastrointestinal problems all require assessment and monitoring in addition to the risk of recurring infections, dental and vision problems, and lymphedema. Finally, all patients should have cognitive, behavioral, and ASD evaluations. The objective of this paper is to address this gap in the literature and establish recommendations to assess the medical, genetic, and neurological features of PMS. En ligne : http://dx.doi.org/10.1186/1866-1955-6-39 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347
in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.39[article] Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring [Texte imprimé et/ou numérique] / A. KOLEVZON, Auteur ; Benjamin ANGARITA, Auteur ; L. BUSH, Auteur ; A. Ting WANG, Auteur ; Y. FRANK, Auteur ; A. YANG, Auteur ; R. RAPAPORT, Auteur ; J. SALAND, Auteur ; S. SRIVASTAVA, Auteur ; C. FARRELL, Auteur ; L. J. EDELMANN, Auteur ; Joseph D. BUXBAUM, Auteur . - p.39.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.39
Mots-clés : 22q13 deletion syndrome Autism Autism spectrum disorder Neurodevelopmental disorders Phelan-McDermid syndrome Practice parameters Shank3 Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) and intellectual disability (ID) can be caused by mutations in a large number of genes. One example is SHANK3 on the terminal end of chromosome 22q. Loss of one functional copy of SHANK3 results in 22q13 deletion syndrome or Phelan-McDermid syndrome (PMS) and causes a monogenic form of ASD and/or ID with a frequency of 0.5% to 2% of cases. SHANK3 is the critical gene in this syndrome, and its loss results in disruption of synaptic function. With chromosomal microarray analyses now a standard of care in the assessment of ASD and developmental delay, and with the emergence of whole exome and whole genome sequencing in this context, identification of PMS in routine clinical settings will increase significantly. However, PMS remains a rare disorder, and the majority of physicians have never seen a case. While there is agreement about core deficits of PMS, there have been no established parameters to guide evaluation and medical monitoring of the syndrome. Evaluations must include a thorough history and physical and dysmorphology examination. Neurological deficits, including the presence of seizures and structural brain abnormalities should be assessed as well as motor deficits. Endocrine, renal, cardiac, and gastrointestinal problems all require assessment and monitoring in addition to the risk of recurring infections, dental and vision problems, and lymphedema. Finally, all patients should have cognitive, behavioral, and ASD evaluations. The objective of this paper is to address this gap in the literature and establish recommendations to assess the medical, genetic, and neurological features of PMS. En ligne : http://dx.doi.org/10.1186/1866-1955-6-39 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347 Language ENvironment Analysis (LENA) in Phelan-McDermid Syndrome: Validity and Suggestions for Use in Minimally Verbal Children with Autism Spectrum Disorder / Jacquelin RANKINE in Journal of Autism and Developmental Disorders, 47-6 (June 2017)
[article]
Titre : Language ENvironment Analysis (LENA) in Phelan-McDermid Syndrome: Validity and Suggestions for Use in Minimally Verbal Children with Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Jacquelin RANKINE, Auteur ; Erin LI, Auteur ; Stacey LURIE, Auteur ; Hillary RIEGER, Auteur ; Emily FOURIE, Auteur ; Paige M. SIPER, Auteur ; A. Ting WANG, Auteur ; Joseph D. BUXBAUM, Auteur ; Alexander KOLEVZON, Auteur Article en page(s) : p.1605-1617 Langues : Anglais (eng) Mots-clés : Phelan-McDermid syndrome 22q13 deletion syndrome Autism spectrum disorder Automated vocal analysis Language ENvironment Analysis Minimally verbal Index. décimale : PER Périodiques Résumé : Phelan-McDermid syndrome (PMS) is a single-locus cause of developmental delay, autism spectrum disorder, and minimal verbal abilities. There is an urgent need to identify objective outcome measures of expressive language for use in this and other minimally verbal populations. One potential tool is an automated language processor called Language ENvironment Analysis (LENA). LENA was used to obtain over 542 h of audio in 18 children with PMS. LENA performance was adequate in a subset of children with PMS, specifically younger children and those with fewer stereotypic vocalizations. One LENA-derived language measure, Vocalization Ratio, had improved accuracy in this sample and may represent a novel expressive language measure for use in severely affected populations. En ligne : http://dx.doi.org/10.1007/s10803-017-3082-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=308
in Journal of Autism and Developmental Disorders > 47-6 (June 2017) . - p.1605-1617[article] Language ENvironment Analysis (LENA) in Phelan-McDermid Syndrome: Validity and Suggestions for Use in Minimally Verbal Children with Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Jacquelin RANKINE, Auteur ; Erin LI, Auteur ; Stacey LURIE, Auteur ; Hillary RIEGER, Auteur ; Emily FOURIE, Auteur ; Paige M. SIPER, Auteur ; A. Ting WANG, Auteur ; Joseph D. BUXBAUM, Auteur ; Alexander KOLEVZON, Auteur . - p.1605-1617.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 47-6 (June 2017) . - p.1605-1617
Mots-clés : Phelan-McDermid syndrome 22q13 deletion syndrome Autism spectrum disorder Automated vocal analysis Language ENvironment Analysis Minimally verbal Index. décimale : PER Périodiques Résumé : Phelan-McDermid syndrome (PMS) is a single-locus cause of developmental delay, autism spectrum disorder, and minimal verbal abilities. There is an urgent need to identify objective outcome measures of expressive language for use in this and other minimally verbal populations. One potential tool is an automated language processor called Language ENvironment Analysis (LENA). LENA was used to obtain over 542 h of audio in 18 children with PMS. LENA performance was adequate in a subset of children with PMS, specifically younger children and those with fewer stereotypic vocalizations. One LENA-derived language measure, Vocalization Ratio, had improved accuracy in this sample and may represent a novel expressive language measure for use in severely affected populations. En ligne : http://dx.doi.org/10.1007/s10803-017-3082-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=308 Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature / A. KOLEVZON in Molecular Autism, 10 (2019)
[article]
Titre : Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature Type de document : Texte imprimé et/ou numérique Auteurs : A. KOLEVZON, Auteur ; E. DELABY, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Joseph D. BUXBAUM, Auteur ; Catalina BETANCUR, Auteur Article en page(s) : 50 p. Langues : Anglais (eng) Mots-clés : 22q13 deletion syndrome Bipolar disorder Catatonia Phelan-McDermid syndrome Psychosis Regression SHANK3 Index. décimale : PER Périodiques Résumé : Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene on chromosome 22q13.33 and is characterized by intellectual disability, hypotonia, severe speech impairments, and autism spectrum disorder. Emerging evidence indicates that there are changes over time in the phenotype observed in individuals with PMS, including severe neuropsychiatric symptoms and loss of skills occurring in adolescence and adulthood. To gain further insight into these phenomena and to better understand the long-term course of the disorder, we conducted a systematic literature review and identified 56 PMS cases showing signs of behavioral and neurologic decompensation in adolescence or adulthood (30 females, 25 males, 1 gender unknown). Clinical presentations included features of bipolar disorder, catatonia, psychosis, and loss of skills, occurring at a mean age of 20 years. There were no apparent sex differences in the rates of these disorders except for catatonia, which appeared to be more frequent in females (13 females, 3 males). Reports of individuals with point mutations in SHANK3 exhibiting neuropsychiatric decompensation and loss of skills demonstrate that loss of one copy of SHANK3 is sufficient to cause these manifestations. In the majority of cases, no apparent cause could be identified; in others, symptoms appeared after acute events, such as infections, prolonged or particularly intense seizures, or changes in the individual's environment. Several individuals had a progressive neurological deterioration, including one with juvenile onset metachromatic leukodystrophy, a severe demyelinating disorder caused by recessive mutations in the ARSA gene in 22q13.33. These reports provide insights into treatment options that have proven helpful in some cases, and are reviewed herein. Our survey highlights how little is currently known about neuropsychiatric presentations and loss of skills in PMS and underscores the importance of studying the natural history in individuals with PMS, including both cross-sectional and long-term longitudinal analyses. Clearer delineation of these neuropsychiatric symptoms will contribute to their recognition and prompt management and will also help uncover the underlying biological mechanisms, potentially leading to improved interventions. En ligne : http://dx.doi.org/10.1186/s13229-019-0291-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414
in Molecular Autism > 10 (2019) . - 50 p.[article] Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature [Texte imprimé et/ou numérique] / A. KOLEVZON, Auteur ; E. DELABY, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Joseph D. BUXBAUM, Auteur ; Catalina BETANCUR, Auteur . - 50 p.
Langues : Anglais (eng)
in Molecular Autism > 10 (2019) . - 50 p.
Mots-clés : 22q13 deletion syndrome Bipolar disorder Catatonia Phelan-McDermid syndrome Psychosis Regression SHANK3 Index. décimale : PER Périodiques Résumé : Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene on chromosome 22q13.33 and is characterized by intellectual disability, hypotonia, severe speech impairments, and autism spectrum disorder. Emerging evidence indicates that there are changes over time in the phenotype observed in individuals with PMS, including severe neuropsychiatric symptoms and loss of skills occurring in adolescence and adulthood. To gain further insight into these phenomena and to better understand the long-term course of the disorder, we conducted a systematic literature review and identified 56 PMS cases showing signs of behavioral and neurologic decompensation in adolescence or adulthood (30 females, 25 males, 1 gender unknown). Clinical presentations included features of bipolar disorder, catatonia, psychosis, and loss of skills, occurring at a mean age of 20 years. There were no apparent sex differences in the rates of these disorders except for catatonia, which appeared to be more frequent in females (13 females, 3 males). Reports of individuals with point mutations in SHANK3 exhibiting neuropsychiatric decompensation and loss of skills demonstrate that loss of one copy of SHANK3 is sufficient to cause these manifestations. In the majority of cases, no apparent cause could be identified; in others, symptoms appeared after acute events, such as infections, prolonged or particularly intense seizures, or changes in the individual's environment. Several individuals had a progressive neurological deterioration, including one with juvenile onset metachromatic leukodystrophy, a severe demyelinating disorder caused by recessive mutations in the ARSA gene in 22q13.33. These reports provide insights into treatment options that have proven helpful in some cases, and are reviewed herein. Our survey highlights how little is currently known about neuropsychiatric presentations and loss of skills in PMS and underscores the importance of studying the natural history in individuals with PMS, including both cross-sectional and long-term longitudinal analyses. Clearer delineation of these neuropsychiatric symptoms will contribute to their recognition and prompt management and will also help uncover the underlying biological mechanisms, potentially leading to improved interventions. En ligne : http://dx.doi.org/10.1186/s13229-019-0291-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 A randomized controlled trial of intranasal oxytocin in Phelan-McDermid syndrome / J. FASTMAN in Molecular Autism, 12 (2021)
[article]
Titre : A randomized controlled trial of intranasal oxytocin in Phelan-McDermid syndrome Type de document : Texte imprimé et/ou numérique Auteurs : J. FASTMAN, Auteur ; J. FOSS-FEIG, Auteur ; Y. FRANK, Auteur ; Danielle B. HALPERN, Auteur ; Hala HARONY-NICOLAS, Auteur ; C. LAYTON, Auteur ; S. SANDIN, Auteur ; P. SIPER, Auteur ; L. TANG, Auteur ; P. TRELLES, Auteur ; J. ZWEIFACH, Auteur ; Joseph D. BUXBAUM, Auteur ; A. KOLEVZON, Auteur Article en page(s) : 62 p. Langues : Anglais (eng) Mots-clés : Asd Autism spectrum disorder Oxytocin Pms Phelan-McDermid syndrome Shank3 Ovid Therapeutics. JDB has a shared patent with Mount Sinai for IGF-1 in Phelan-McDermid syndrome. No other authors have competing interests to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene and characterized by global developmental delays, deficits in speech and motor function, and autism spectrum disorder (ASD). Monogenic causes of ASD such as PMS are well suited to investigations with novel therapeutics, as interventions can be targeted based on established genetic etiology. While preclinical studies have demonstrated that the neuropeptide oxytocin can reverse electrophysiological, attentional, and social recognition memory deficits in Shank3-deficient rats, there have been no trials in individuals with PMS. The purpose of this study is to assess the efficacy and safety of intranasal oxytocin as a treatment for the core symptoms of ASD in a cohort of children with PMS. METHODS: Eighteen children aged 5-17 with PMS were enrolled. Participants were randomized to receive intranasal oxytocin or placebo (intranasal saline) and underwent treatment during a 12-week double-blind, parallel group phase, followed by a 12-week open-label extension phase during which all participants received oxytocin. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as a number of secondary outcome measures related to the core symptoms of ASD. Safety was monitored throughout the study period. RESULTS: There was no statistically significant improvement with oxytocin as compared to placebo on the ABC-SW (Mann-Whitney U?=?50, p?=?0.055), or on any secondary outcome measures, during either the double-blind or open-label phases. Oxytocin was generally well tolerated, and there were no serious adverse events. LIMITATIONS: The small sample size, potential challenges with drug administration, and expectancy bias due to relying on parent reported outcome measures may all contribute to limitations in interpreting results. CONCLUSION: Our results suggest that intranasal oxytocin is not efficacious in improving the core symptoms of ASD in children with PMS. Trial registration NCT02710084. En ligne : http://dx.doi.org/10.1186/s13229-021-00459-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 12 (2021) . - 62 p.[article] A randomized controlled trial of intranasal oxytocin in Phelan-McDermid syndrome [Texte imprimé et/ou numérique] / J. FASTMAN, Auteur ; J. FOSS-FEIG, Auteur ; Y. FRANK, Auteur ; Danielle B. HALPERN, Auteur ; Hala HARONY-NICOLAS, Auteur ; C. LAYTON, Auteur ; S. SANDIN, Auteur ; P. SIPER, Auteur ; L. TANG, Auteur ; P. TRELLES, Auteur ; J. ZWEIFACH, Auteur ; Joseph D. BUXBAUM, Auteur ; A. KOLEVZON, Auteur . - 62 p.
Langues : Anglais (eng)
in Molecular Autism > 12 (2021) . - 62 p.
Mots-clés : Asd Autism spectrum disorder Oxytocin Pms Phelan-McDermid syndrome Shank3 Ovid Therapeutics. JDB has a shared patent with Mount Sinai for IGF-1 in Phelan-McDermid syndrome. No other authors have competing interests to disclose. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene and characterized by global developmental delays, deficits in speech and motor function, and autism spectrum disorder (ASD). Monogenic causes of ASD such as PMS are well suited to investigations with novel therapeutics, as interventions can be targeted based on established genetic etiology. While preclinical studies have demonstrated that the neuropeptide oxytocin can reverse electrophysiological, attentional, and social recognition memory deficits in Shank3-deficient rats, there have been no trials in individuals with PMS. The purpose of this study is to assess the efficacy and safety of intranasal oxytocin as a treatment for the core symptoms of ASD in a cohort of children with PMS. METHODS: Eighteen children aged 5-17 with PMS were enrolled. Participants were randomized to receive intranasal oxytocin or placebo (intranasal saline) and underwent treatment during a 12-week double-blind, parallel group phase, followed by a 12-week open-label extension phase during which all participants received oxytocin. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as a number of secondary outcome measures related to the core symptoms of ASD. Safety was monitored throughout the study period. RESULTS: There was no statistically significant improvement with oxytocin as compared to placebo on the ABC-SW (Mann-Whitney U?=?50, p?=?0.055), or on any secondary outcome measures, during either the double-blind or open-label phases. Oxytocin was generally well tolerated, and there were no serious adverse events. LIMITATIONS: The small sample size, potential challenges with drug administration, and expectancy bias due to relying on parent reported outcome measures may all contribute to limitations in interpreting results. CONCLUSION: Our results suggest that intranasal oxytocin is not efficacious in improving the core symptoms of ASD in children with PMS. Trial registration NCT02710084. En ligne : http://dx.doi.org/10.1186/s13229-021-00459-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case / C. I. SAMOGY-COSTA in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)
[article]
Titre : A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case Type de document : Texte imprimé et/ou numérique Auteurs : C. I. SAMOGY-COSTA, Auteur ; E. VARELLA-BRANCO, Auteur ; F. MONFARDINI, Auteur ; H. FERRAZ, Auteur ; R. A. FOCK, Auteur ; R. H. A. BARBOSA, Auteur ; A. L. S. PESSOA, Auteur ; A. B. A. PEREZ, Auteur ; N. LOURENCO, Auteur ; M. VIBRANOVSKI, Auteur ; A. KREPISCHI, Auteur ; C. ROSENBERG, Auteur ; M. R. PASSOS-BUENO, Auteur Article en page(s) : 13 p. Langues : Anglais (eng) Mots-clés : 22q13.3 deletion syndrome Autism spectrum disorder Phelan-McDermid syndrome Shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms associated with several comorbidities caused by SHANK3 loss-of-function mutations. Although SHANK3 haploinsufficiency has been associated with the major neurological symptoms of PMS, it cannot explain the clinical variability seen among individuals. Our goals were to characterize a Brazilian cohort of PMS individuals, explore the genotype-phenotype correlation underlying this syndrome, and describe an atypical individual with mild phenotype. METHODOLOGY: A total of 34 PMS individuals were clinically and genetically evaluated. Data were obtained by a questionnaire answered by parents, and dysmorphic features were assessed via photographic evaluation. We analyzed 22q13.3 deletions and other potentially pathogenic copy number variants (CNVs) and also performed genotype-phenotype correlation analysis to determine whether comorbidities, speech status, and ASD correlate to deletion size. Finally, a Brazilian cohort of 829 ASD individuals and another independent cohort of 2297 ID individuals was used to determine the frequency of PMS in these disorders. RESULTS: Our data showed that 21% (6/29) of the PMS individuals presented an additional rare CNV, which may contribute to clinical variability in PMS. Increased pain tolerance (80%), hypotonia (85%), and sparse eyebrows (80%) were prominent clinical features. An atypical case diagnosed with PMS at 18 years old and IQ within the normal range is here described. Among Brazilian ASD or ID individuals referred to CNV analyses, the frequency of 22q13.3 deletion was 0.6% (5/829) and 0.61% (15/2297), respectively. Finally, renal abnormalities, lymphedema, and language impairment were found to be positively associated with deletion sizes, and the minimum deletion to cause these abnormalities is here suggested. CONCLUSIONS: This is the first work describing a cohort of Brazilian individuals with PMS. Our results confirm the impact of 22q13 deletions on ASD and several comorbidities, such as hypotonia. The estimation of a minimal deletion size for developing lymphedema and renal problem can assist prediction of prognosis in PMS individuals, particularly those diagnosed in early infancy. We also identified one atypical individual carrying SHANK3 deletion, suggesting that resilience to such mutations occurs. This case expands the clinical spectrum of variability in PMS and opens perspectives to identify protective mechanisms that can minimize the severity of this condition. En ligne : https://dx.doi.org/10.1186/s11689-019-9273-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409
in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 13 p.[article] A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case [Texte imprimé et/ou numérique] / C. I. SAMOGY-COSTA, Auteur ; E. VARELLA-BRANCO, Auteur ; F. MONFARDINI, Auteur ; H. FERRAZ, Auteur ; R. A. FOCK, Auteur ; R. H. A. BARBOSA, Auteur ; A. L. S. PESSOA, Auteur ; A. B. A. PEREZ, Auteur ; N. LOURENCO, Auteur ; M. VIBRANOVSKI, Auteur ; A. KREPISCHI, Auteur ; C. ROSENBERG, Auteur ; M. R. PASSOS-BUENO, Auteur . - 13 p.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 13 p.
Mots-clés : 22q13.3 deletion syndrome Autism spectrum disorder Phelan-McDermid syndrome Shank3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms associated with several comorbidities caused by SHANK3 loss-of-function mutations. Although SHANK3 haploinsufficiency has been associated with the major neurological symptoms of PMS, it cannot explain the clinical variability seen among individuals. Our goals were to characterize a Brazilian cohort of PMS individuals, explore the genotype-phenotype correlation underlying this syndrome, and describe an atypical individual with mild phenotype. METHODOLOGY: A total of 34 PMS individuals were clinically and genetically evaluated. Data were obtained by a questionnaire answered by parents, and dysmorphic features were assessed via photographic evaluation. We analyzed 22q13.3 deletions and other potentially pathogenic copy number variants (CNVs) and also performed genotype-phenotype correlation analysis to determine whether comorbidities, speech status, and ASD correlate to deletion size. Finally, a Brazilian cohort of 829 ASD individuals and another independent cohort of 2297 ID individuals was used to determine the frequency of PMS in these disorders. RESULTS: Our data showed that 21% (6/29) of the PMS individuals presented an additional rare CNV, which may contribute to clinical variability in PMS. Increased pain tolerance (80%), hypotonia (85%), and sparse eyebrows (80%) were prominent clinical features. An atypical case diagnosed with PMS at 18 years old and IQ within the normal range is here described. Among Brazilian ASD or ID individuals referred to CNV analyses, the frequency of 22q13.3 deletion was 0.6% (5/829) and 0.61% (15/2297), respectively. Finally, renal abnormalities, lymphedema, and language impairment were found to be positively associated with deletion sizes, and the minimum deletion to cause these abnormalities is here suggested. CONCLUSIONS: This is the first work describing a cohort of Brazilian individuals with PMS. Our results confirm the impact of 22q13 deletions on ASD and several comorbidities, such as hypotonia. The estimation of a minimal deletion size for developing lymphedema and renal problem can assist prediction of prognosis in PMS individuals, particularly those diagnosed in early infancy. We also identified one atypical individual carrying SHANK3 deletion, suggesting that resilience to such mutations occurs. This case expands the clinical spectrum of variability in PMS and opens perspectives to identify protective mechanisms that can minimize the severity of this condition. En ligne : https://dx.doi.org/10.1186/s11689-019-9273-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome / A. KOLEVZON in Molecular Autism, 13 (2022)
PermalinkDelineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations / S. DE RUBEIS in Molecular Autism, 9 (2018)
PermalinkDevelopmental phenotype in Phelan-McDermid (22q13.3 deletion) syndrome: a systematic and prospective study in 34 children / R. J. ZWANENBURG in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)
PermalinkProspective study of autism phenomenology and the behavioural phenotype of Phelan-McDermid syndrome: comparison to fragile X syndrome, Down syndrome and idiopathic autism spectrum disorder / C. RICHARDS in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)
PermalinkPsychometric Study of the Social Responsiveness Scale in Phelan-McDermid Syndrome / Kellie GERGOUDIS in Autism Research, 13-8 (August 2020)
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