Article
Psychiatry
Annemiek M. Landlust, Linda Visser, Boudien C. T. Flapper, Selma A. J. Ruiter, Renee J. Zwanenburg, Conny M. A. van Ravenswaaij-Arts, Ingrid D. C. van Balkom
Summary: Our study describes a structured multidisciplinary method of assessment for individuals with PMS, combining direct in-person neurodevelopmental assessments with assessment of contextual factors. The results show variability in behavior, symptom expression, and severity in individuals with PMS, highlighting the importance of considering the individual's cognitive and adaptive development and the genetic context when interpreting behavioral data. The study also suggests that combining questionnaires with direct in-person assessments provides a more accurate method for interpreting findings and understanding behavior in rare genetic disorders associated with developmental delay such as PMS.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Genetics & Heredity
Francisco Cammarata-Scalisi, Michele Callea, Diego Martinelli, Colin Eric Willoughby, Antonio Cardenas Tadich, Maykol Araya Castillo, Maria Angelina Lacruz-Rengel, Marco Medina, Piercesare Grimaldi, Enrico Bertini, Julian Nevado
Summary: Phelan-McDermid syndrome is a rare and complex neurodevelopmental disorder caused by microdeletion or mutations in the SHANK3 gene on chromosome 22. The clinical presentation is variable, and diagnosis requires genetic analysis and multidisciplinary care.
Article
Pediatrics
Liang Chen, Zhi-ye Yao, Xiangtao Wu, Shao-ru He, Yu-mei Liu, Xue-yan Wang, De-zhi Cao, Xing-kun Yang, Jian-bo Zhao, Zi Ren, Hong Li, Zheng Pei, Hong-ke Ding, Zhi-chun Feng
Summary: This study evaluated ten Chinese pediatric patients with Phelan-McDermid syndrome (PMS) and found novel mutations in all patients. Three patients had mutations or deletions in the SHANK3 gene. The findings of this study provide a reference for clinical research and PMS diagnosis.
FRONTIERS IN PEDIATRICS
(2022)
Article
Psychology, Developmental
Paige M. Siper, Mikaela A. Rowe, Sylvia B. Guillory, Audrey A. Rouhandeh, Julia L. George-Jones, Teresa Tavassoli, Stacey Lurie, Jessica Zweifach, Jordana Weissman, Jennifer Foss-Feig, Danielle Halpern, M. Pilar Trelles, Maureen S. Mulhern, Chloe Brittenham, James Gordon, Vance Zemon, Joseph D. Buxbaum, Alexander Kolevzon
Summary: This study examined excitatory and inhibitory postsynaptic activity in children with Phelan-McDermid syndrome (PMS) using visual evoked potentials (VEPs) and explored the association with genetic factors. The results showed distinct VEP waveform abnormalities in children with PMS, which might reflect underlying glutamatergic deficits associated with deletion size. VEPs offer a noninvasive measure that holds promise for clinical trials in PMS and ASD.
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
(2022)
Article
Genetics & Heredity
Julian Nevado, Sixto Garcia-Minaur, Maria Palomares-Bralo, Elena Vallespin, Encarna Guillen-Navarro, Jordi Rosell, Cristina Bel-Fenellos, Maria Angeles Mori, Montserrat Mila, Miguel del Campo, Pilar Barruz, Fernando Santos-Simarro, Gabriela Obregon, Carmen Orellana, Harry Pachajoa, Jair Antonio Tenorio, Enrique Galan, Juan C. Cigudosa, Angelica Moresco, Cesar Saleme, Silvia Castillo, Elisabeth Gabau, Luis Perez-Jurado, Ana Barcia, Maria Soledad Martin, Elena Mansilla, Isabel Vallcorba, Pedro Garcia-Murillo, Franco Cammarata-Scalisi, Natalya Goncalves Pereira, Raquel Blanco-Lago, Mercedes Serrano, Juan Dario Ortigoza-Escobar, Blanca Gener, Veronica Adriana Seidel, Pilar Tirado, Pablo Lapunzina
Summary: This study describes a cohort of 210 patients with genetically confirmed Phelan-McDermid syndrome (PMS) and identifies multiple variant types, including small deletions and SHANK3 sequence variants. The findings suggest that SHANK3 plays an important role in PMS, but is probably not solely responsible for all the spectrum features.
FRONTIERS IN GENETICS
(2022)
Article
Oncology
L. C. Schenkel, E. Aref-Eshghi, K. Rooney, J. Kerkhof, M. A. Levy, H. McConkey, R. C. Rogers, K. Phelan, S. M. Sarasua, L. Jain, R. Pauly, L. Boccuto, B. DuPont, G. Cappuccio, N. Brunetti-Pierri, C. E. Schwartz, B. Sadikovic
Summary: We identified a novel genome-wide DNA methylation epi-signature in a subset of individuals with Phelan-McDermid syndrome. The critical region responsible for this epi-signature was found to include the BRD1 gene. Metabolomic profiles of individuals with this epi-signature indicated the presence of two distinct clinical subtypes of Phelan-McDermid syndrome.
CLINICAL EPIGENETICS
(2021)
Article
Clinical Neurology
Yitzchak Frank
Summary: Phelan-McDermid syndrome (PMS) is a genetic disorder caused by haploinsufficiency of the SHANK3 gene. It is characterized by neurobehavioral symptoms and signs including intellectual disability, speech and language impairment, and autism spectrum disorder. Advances in understanding the pathophysiology and generation of animal models have raised opportunities for a biological cure for PMS.
PEDIATRIC NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Amanda Brignell, Conway Gu, Alison Holm, Bronwyn Carrigg, Daisy A. Sheppard, David J. Amor, Angela T. Morgan
Summary: Communication difficulties are common in individuals with Phelan-McDermid syndrome, with 45% being non-verbal. Adaptive behavior is notably low in all areas, particularly in communication compared to daily living and socialization.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Review
Pediatrics
Yasunari Sakai, Sayaka Okuzono, Christian P. Schaaf, Shouichi Ohga
Summary: Phelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by developmental delay, epilepsy, and autism spectrum disorder (ASD), linked to the SHANK3 gene. Researchers utilize iPS cells and brain organoids to delve into the pathophysiology of neurodevelopmental disorders, while single-cell RNA sequencing reveals unique roles of patient-derived disease models in human brain development.
PEDIATRIC RESEARCH
(2022)
Article
Genetics & Heredity
Marie S. Smith, Sara M. Sarasua, Curtis Rogers, Katy Phelan, Luigi Boccuto
Summary: This study investigated the prevalence of lymphedema in Phelan-McDermid syndrome (PMS) patients and found a higher incidence rate in patients with 22q13.3 deletions associated with PMS. Patients in their teens or adulthood and those with deletions >4Mb were more likely to have lymphedema.
Article
Genetics & Heredity
Lavanya Jain, Lindsay M. Oberman, Laura Beamer, Lauren Cascio, Melanie May, Sujata Srikanth, Cindy Skinner, Kelly Jones, Bridgette Allen, Curtis Rogers, Katy Phelan, Walter E. Kaufmann, Barbara DuPont, Sara M. Sarasua, Luigi Boccuto
Summary: This study investigated the prevalence of seizures and their association with genetic and metabolic features in Phelan-McDermid syndrome (PMS) patients. Results showed that individuals with pathogenic SHANK3 mutations had the highest prevalence of seizures, and the gene TBC1D22A in the 22q13.31 region was significantly associated with seizure prevalence. Additionally, a distinct metabolic profile was identified for PMS patients with seizures, indicating a disrupted utilization of main energy sources.
Letter
Genetics & Heredity
A. Kolevzon, M. S. Breen, P. M. Siper, D. Halpern, Y. Frank, H. Rieger, J. Weismann, M. P. Trelles, B. Lerman, R. Rapaport, J. D. Buxbaum
Summary: This study evaluates the therapeutic effect of IGF-1 on core symptoms of ASD in children with PMS. The results show that IGF-1 can improve sensory reactivity symptoms, repetitive behaviors, and hyperactivity.
Article
Genetics & Heredity
Bridgette A. A. Moffitt, Lindsay M. M. Oberman, Laura Beamer, Sujata Srikanth, Lavanya Jain, Lauren Cascio, Kelly Jones, Rini Pauly, Melanie May, Cindy Skinner, Caroline Buchanan, Barbara R. R. DuPont, Walter E. E. Kaufmann, Kathleen Valentine, Linda D. D. Ward, Diana Ivankovic, R. Curtis Rogers, Katy Phelan, Sara M. M. Sarasua, Luigi Boccuto
Summary: This study investigated the prevalence of sleep disturbances in individuals with Phelan-McDermid Syndrome (PMS) and examined the genetic and metabolic features associated with them. The results showed that sleep disturbances were present in 64.3% of PMS patients, with the most common problem being waking during the night. Individuals with a SHANK3 pathogenic variant had a higher prevalence of sleep disturbances compared to those with 22q13.3 deletions. Distinct metabolic profiles for PMS patients with and without sleep disturbances were also identified.
Article
Neurosciences
Emily L. Isenstein, Hannah E. Grosman, Sylvia B. Guillory, Yian Zhang, Sarah Barkley, Christopher S. McLaughlin, Tess Levy, Danielle Halpern, Paige M. Siper, Joseph D. Buxbaum, Alexander Kolevzon, Jennifer H. Foss-Feig
Summary: This study investigated neural markers of hyporesponsiveness in individuals with Phelan-McDermid Syndrome (PMS) using electrophysiology and a passive auditory habituation paradigm. The results showed that while both individuals with idiopathic ASD (iASD) and PMS displayed intact neural responses and habituation to simple auditory stimuli, greater initial N1 amplitude and habituation were associated with auditory hypersensitivity and ASD symptomatology in the PMS group. Further classification based on genetic groupings revealed dissociation of initial P2 amplitude and habituation of N1 depending on the presence of additional genes beyond SHANK3. These initial findings suggest that genotypic and phenotypic characteristics may contribute to the variability in auditory processing in PMS.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Pediatrics
Cristina Garcia-Bravo, Rosa Ma Martinez-Piedrola, Sara Garcia-Bravo, Ma Pilar Rodriguez-Perez, Ana San Martin-Gomez, Gemma Fernandez-Gomez, Domingo Palacios-Cena
Summary: This study aimed to describe the experiences of parents of children diagnosed with Phelan-McDermid syndrome (PMS) in relation to epileptic seizures and/or convulsions, and to explore their impact on daily life. Data was collected through in-depth interviews and analyzed thematically. Four themes were identified: the first epileptic seizure, living with seizures, treatment of epileptic seizures, and the impact of epilepsy on the family. The study concludes that programs should be developed to facilitate discussion between parents and professionals regarding treatment decisions and provide coping strategies for managing epilepsy and seizures.
EUROPEAN JOURNAL OF PEDIATRICS
(2023)