Review
Neurosciences
Ilaria Parenti, Frank J. Kaiser
Summary: Chromatinopathies are neurodevelopmental disorders caused by mutations in proteins responsible for chromatin remodeling and transcriptional regulation, resulting in dysregulation of gene expression and clinical features such as developmental delay and intellectual disability. CdLS is a typical example, primarily caused by mutations in cohesin complex subunits or regulators, but also by variants in non-cohesin genes with similar functions.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Pablo Garcia-Gutierrez, Mario Garcia-Dominguez
Summary: CdLS is a human developmental syndrome that may be a transcriptomopathy related to transcriptional regulation, altered cohesin complex function, and mutations in NIPBL. The pathogenesis of CdLS is likely primarily based on changes in gene expression programs.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Endocrinology & Metabolism
Yiding Shen, Dongyan Zhao, Long Sun, Xiuzhen Yang, Xiang Yan
Summary: Cornelia de Lange syndrome (CdLS) is a rare genetic disease with limited information on female genital abnormalities. Timely identification and treatment of genital abnormalities in female CdLS patients are crucial for symptom improvement, reducing complications, and controlling recurrent infections.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Genetics & Heredity
Paola Francesca Ajmone, Ludovica Giani, Beatrice Allegri, Giovanni Michelini, Francesca Dall'Ara, Claudia Rigamonti, Federico Monti, Paola Giovanna Vizziello, Angelo Selicorni, Donatella Milani, Simona Scaini, Antonella Costantino
Summary: Behavioral changes occur in children with Cornelia de Lange Syndrome (CdLS) and Rubinstein-Taybi Syndrome (RSTS). A longitudinal study was conducted to explore the changes in neuropsychiatric functioning across the lifespan. The study found that CdLS patients experience a worsening trend in cognitive profile, while RSTS patients maintain stable cognitive abilities. RSTS patients show greater improvements in communication, daily living skills, social abilities, and motor skills. Both syndromes exhibit an upward trend in behavioral and emotional difficulties, but CdLS patients show a significant deterioration compared to RSTS individuals.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
M. J. Pablo, P. Pamplona, M. Haddad, I Benavente, A. Latorre-Pellicer, M. Arnedo, L. Trujillano, G. Bueno-Lozano, L. M. Kerr, S. A. Huisman, F. J. Kaiser, F. Ramos, A. D. Kline, J. Pie, B. Puisac
Summary: This study found that autonomic nervous system dysfunction is present in many individuals with Cornelia de Lange Syndrome, which may be related to premature aging.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Pediatrics
Huakun Shangguan, Ruimin Chen
Summary: This study describes six variants in non-cohesion genes and evaluates the reliability of the 11-point clinical scoring criteria for the diagnosis of Cornelia de Lange syndrome (CdLS). The results show significant differences in clinical scores between patients with variants in non-cohesion genes and those with NIPBL variants. This study expands the spectrum of non-cohesion gene variations in CdLS patients.
FRONTIERS IN PEDIATRICS
(2022)
Review
Psychiatry
Laura Groves, Chris Oliver, Joanna Moss
Summary: Recent studies have found varying presentations of the behavioural phenotype of CdLS across the lifespan, with autistic characteristics and behaviors related to compromised mental health being more common and severe in older individuals. Further research is needed to thoroughly document the behavioral phenotype of CdLS patients and consider multiple factors that may influence negative outcomes.
CURRENT OPINION IN PSYCHIATRY
(2021)
Article
Cell & Tissue Engineering
Alessandro Umbach, Giulia Maule, Eyemen Kheir, Alessandro Cutarelli, Marika Foglia, Luca Guarrera, Luca L. Fava, Luciano Conti, Enrico Garattini, Mineko Terao, Anna Cereseto
Summary: This study presents an efficient method of repairing the NIPBL gene using CRISPR-Cas and HDR induced by inhibiting NHEJ repair. The generated isogenic hiPSCs clones possess regular karyotype and preserved pluripotency.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Genetics & Heredity
Maninder Kaur, Justin Blair, Batsal Devkota, Sierra Fortunato, Dinah Clark, Audrey Lawrence, Jiwoo Kim, Wonwook Do, Benjamin Semeo, Olivia Katz, Devanshi Mehta, Nobuko Yamamoto, Emma Schindler, Zayd Al Rawi, Nina Wallace, Jonathan J. Wilde, Jennifer McCallum, Jinglan Liu, Dongbin Xu, Marie McDonald, Stefan Rentas, Ahmad Abou Tayoun, Zhang Zhe, Omar Abdul-Rahman, Bill Allen, Moris A. Angula, Kwame Anyane-Yeboa, Jesus Argente, Pamela H. Arn, Linlea Armstrong, Lina Basel-Salmon, Gareth Baynam, Lynne M. Bird, Daniel Bruegger, Gaik-Siew Ch'ng, David Chitayat, Robin Clark, Gerald F. Cox, Usha Dave, Elfrede DeBaere, Michael Field, John M. Graham, Karen W. Gripp, Robert Greenstein, Neerja Gupta, Randy Heidenreich, Jodi Hoffman, Robert J. Hopkin, Kenneth L. Jones, Marilyn C. Jones, Ariana Kariminejad, Jillene Kogan, Baiba Lace, Julian Leroy, Sally Ann Lynch, Marie McDonald, Kirsten Meagher, Nancy Mendelsohn, Ieva Micule, John M. Toimie, Sheela Nampoothiri, Kaoru Ohashi, Cynthia M. Powell, Subhadra Ramanathan, Salmo Raskin, Elizabeth Roeder, Marlene Rio, Alan F. Rope, Karan Sangha, Angela E. Scheuerle, Adele Schneider, Stavit Shalev, Victoria Siu, Rosemarie Smith, Cathy Stevens, Tinatin Tkemaladze, John Toimie, Helga Toriello, Anne Turner, Patricia G. Wheeler, Susan M. White, Terri Young, Kathleen M. Loomes, Mary Pipan, Ann Tokay Harrington, Elaine Zackai, Ramakrishnan Rajagopalan, Laura Conlin, Matthew A. Deardorff, Deborah McEldrew, Juan Pie, Feliciano Ramos, Antonio Musio, Antonie D. Kline, Kosuke Izumi, Sarah E. Raible, Ian D. Krantz
Summary: Cornelia de Lange Syndrome (CdLS) is a rare developmental disorder characterized by variable manifestations of growth and developmental delays, involving multiple systems and caused by pathogenic variants in genes encoding cohesin complex proteins. The majority of cases are attributed to variants in the NIPBL gene. Other cohesin genes and additional genes such as ANKRD11, EP300, AFF4, TAF1, and BRD4 may also contribute to a CdLS-like phenotype. Understanding the genetic landscape of this population through comprehensive molecular analysis is essential for genotype-phenotype correlations and identification of novel candidate genes.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Beatrice Conti, Berardo Rinaldi, Martina Rimoldi, Roberta Villa, Maria Iascone, Silvana Gangi, Matteo Porro, Paola Francesca Ajmone, Anna Maria Colli, Fabio Mosca, Maria Francesca Bedeschi
Summary: Cornelia de Lange syndrome (CdLS) is a rare congenital neurodevelopmental disorder characterized by facial anomalies, short stature, developmental delay, gastrointestinal abnormalities, and limb defects. This report describes a familial case of CdLS-like presentation and identifies a likely pathogenic variant in the PHIP gene associated with Chung-Jansen syndrome. The findings suggest including PHIP among genes routinely analyzed in patients with CdLS spectrum.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Yin Peng, Ying Zhu, Lin Wu, Fang Deng
Summary: This study reported a novel variant in the MAU2 gene in a Chinese patient with CdLS, strengthening the association between MAU2 variants and CdLS phenotypes. The study suggests that MAU2 should be included in the gene screening list for CdLS.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Obstetrics & Gynecology
Qiu-Xia Yu, Xiang-Yi Jing, Xiao-Mei Lin, Li Zhen, Dong-Zhi Li
Summary: This retrospective study analyzed the clinical and laboratory data of 13 cases diagnosed with CdLS through prenatal and postnatal genetic testing and physical examination. The study found that NIPBL variants were the most common cause of CdLS, followed by SMC1A and HDAC8 variants. Prenatal ultrasound scans helped detect abnormalities in some cases, but non-classic CdLS remained challenging to diagnose solely based on ultrasound examination.
EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Rie Seyama, Yuri Uchiyama, Jose Ricard Magliocco Ceroni, Veronica Eun Hue Kim, Isabel Furquim, Rachel Sayuri Honjo, Matheus Augusto Araujo Castro, Lucas Vieira Lacerda Pires, Hiromi Aoi, Kazuhiro Iwama, Kohei Hamanaka, Atsushi Fujita, Naomi Tsuchida, Eriko Koshimizu, Kazuharu Misawa, Satoko Miyatake, Takeshi Mizuguchi, Shintaro Makino, Atsuo Itakura, Debora R. Bertola, Chong Ae Kim, Naomichi Matsumoto
Summary: Recent studies have found significant overlap in transcript isoforms between brain tissue and Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs). Highly expressed cohesion-related genes in both brain and LCLs are associated with Cornelia de Lange Syndrome (CdLS). RNA sequencing of LCLs proved to be useful in identifying hidden variants in exome-negative cases, as several new pathogenic variants were identified using this method.
Article
Cell & Tissue Engineering
Zilong Li, Chen Liu, Hongmei Xin, Yanan Yang, Yanxin Wang, Shasha Niu, Chunlai Gao, Zhongtao Gai, Yi Liu
Summary: In this study, iPSCs were successfully established from a young male patient with Cornelia de Lange Syndrome and a HDAC8 mutation. The established iPSCs exhibited typical pluripotent stem cell characteristics and retained the HDAC8 mutation. These findings provide valuable insights into the disease pathology and potential therapeutic strategies.
STEM CELL RESEARCH
(2023)
Article
Nursing
Gabrielle N. Deschamps
Summary: Cornelia de Lange syndrome is a rare, multifactorial, multisystem disorder associated with the cohesin complex, with a wide range of phenotypes. Early diagnosis and management are crucial for improving quality of life for patients.
Article
Psychiatry
Sarah J. White, Denise Gerber, Romina D. Sanchez Hernandez, Anthonia Efiannayi, Ishita Chowdhury, Hannah Partington, Joanna F. Moss
Summary: Research on women with the fragile-X premutation has shown that they have an increased risk for autistic traits and anxiety, which is specifically related to the presence of the premutation and not fully explained by maternal status or the stress of caring for children with neurodevelopmental disorders.
BRITISH JOURNAL OF PSYCHIATRY
(2021)
Review
Psychiatry
Laura Groves, Chris Oliver, Joanna Moss
Summary: Recent studies have found varying presentations of the behavioural phenotype of CdLS across the lifespan, with autistic characteristics and behaviors related to compromised mental health being more common and severe in older individuals. Further research is needed to thoroughly document the behavioral phenotype of CdLS patients and consider multiple factors that may influence negative outcomes.
CURRENT OPINION IN PSYCHIATRY
(2021)
Review
Clinical Neurology
M. Marlborough, A. Welham, C. Jones, S. Reckless, J. Moss
Summary: The prevalence of ASD in females with FXS is reliably higher than in the general population, but the characteristic profiles of impairment are not clear. Possible associations between ASD traits and IQ, and between ASD and levels of fragile X mental retardation protein, are suggested, but data are equivocal.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2021)
Article
Psychology, Developmental
Jenny Sloneem, Jo Moss, Sebastian Powell, Christina Hawkins, Tang Fosi, Hanna Richardson, Sarah Aylett
Summary: A study found that children with Sturge-Weber syndrome had relative strengths in social awareness and social motivation, with some showing significant social communication difficulties even without a clinical diagnosis of autism. Therefore, screening for social communication difficulties in this population is recommended to provide timely support.
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2022)
Article
Clinical Neurology
Stacey Bissell, Chris Oliver, Joanna Moss, Mary Heald, Jane Waite, Hayley Crawford, Vishakha Kothari, Lauren Rumbellow, Grace Walters, Caroline Richards
Summary: The study found that patients with SATB2-associated syndrome have a distinct profile of repetitive and autistic behaviors, different from Angelman syndrome and non-syndromal autism. Male patients showed higher rates of overactivity and higher general anxiety scores compared to females.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2022)
Article
Education, Special
Victoria Perry, Katherine Ellis, Jo Moss, Sarah R. Beck, Gursharan Singla, Hayley Crawford, Jane Waite, Caroline Richards, Chris Oliver
Summary: This study describes the behavioral profiles of individuals with Cornelia de Lange (CdLS), fragile X (FXS), Rubinstein-Taybi syndromes (RTS), and autism (AUT), and explores the relationship between executive function behaviors and autistic traits. The results show impairments in executive function behaviors in all groups, with differences in the manifestation of repetitive behaviors and restricted interests between syndrome groups and the AUT group.
RESEARCH IN DEVELOPMENTAL DISABILITIES
(2022)
Review
Clinical Neurology
Andrea T. Thomas, Jane Waite, Caitlin A. Williams, Jeremy Kirk, Chris Oliver, Caroline Richards
Summary: This meta-analysis provides a comprehensive review of clinical features, behavioral, psychological, cognitive, and physical characteristics, conditions, and comorbidities in CHARGE syndrome, laying an empirically based foundation for further research and practice.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2022)
Article
Clinical Neurology
Laura Groves, Joanna Moss, Chris Oliver, Rachel Royston, Jane Waite, Hayley Crawford
Summary: The study examined the prevalence and characteristics of anxiety symptoms in individuals with intellectual disability, finding that high-risk genetic disorders such as CdLS and FXS are associated with both DSM-5 and ASD-related anxiety. Anxiety symptoms persist over time in these groups, with anxiety types partially associated with repetitive behavior.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2022)
Article
Education, Special
C. Laverty, G. Agar, L. Sinclair-Burton, C. Oliver, J. Moss, L. Nelson, C. Richards
Summary: A longitudinal study on individuals with autism over a period of 10 years found that aggressive behaviors are common but decrease with age. Behavioral correlates of attention deficit hyperactivity disorder (ADHD) predict the presence and persistence of aggressive behavior, which can be useful in directing proactive intervention resources to alleviate aggressive behaviors.
JOURNAL OF INTELLECTUAL DISABILITY RESEARCH
(2023)
Review
Psychology, Developmental
Lauren Jenner, Caroline Richards, Rachel Howard, Joanna Moss
Summary: This review discusses the elevated prevalence of autism characteristics in genetic syndromes associated with intellectual disability. Recent findings indicate that the behavioural heterogeneity of autism in these syndromes may have some degree of syndrome specificity, which interacts with broader behavioural phenotypes, intellectual disability, and mental health. The genetic subtype and co-occurring epilepsy within syndromes contribute to the increased significance of autism characteristics. Existing screening/diagnostic tools and criteria lack sensitivity and specificity within these populations, leading to the potential overlooking or misunderstanding of autism-related strengths and challenges.
CURRENT DEVELOPMENTAL DISORDERS REPORTS
(2023)
Article
Psychology, Developmental
Lauren Shelley, Jane Waite, Joanne Tarver, Chris Oliver, Hayley Crawford, Caroline Richards, Stacey Bissell
Summary: SATB2-associated syndrome (SAS) is a genetic syndrome characterized by intellectual disability, severe speech delay, and palatal and dental problems. This study explores the correlates of self-injury, aggression, and property destruction in individuals with SAS. It found that there are specific individual characteristics associated with each behavior, emphasizing the importance of specificity when studying challenging behaviors. Understanding these correlates has important implications for behavioral interventions in SAS.
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2023)
Review
Clinical Neurology
L. A. Jenner, E. K. Farran, A. Welham, C. Jones, J. Moss
Summary: Relatively little is known about social cognition in people with ID and its association with co-occurring autism. Traditional social-cognitive tasks are not suitable for people with ID and lack sensitivity. Eye-tracking technology offers an effective method to study social cognition in ID and has shown a negative correlation between visual attention on SSRs and autism characteristics. Further research is needed to explore additional covariates and determine the specificity of the association.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2023)
Article
Education, Special
E. Pearson, E. Nielsen, S. Kita, L. Groves, L. Nelson, J. Moss, C. Oliver
Summary: The study found that individuals with CdLS use gestures more frequently compared to DS and TD groups, indicating a unique feature in expressive communication for CdLS individuals even with impaired spoken language.
JOURNAL OF INTELLECTUAL DISABILITY RESEARCH
(2021)
Review
Education, Special
C. Eaton, J. Tarver, A. Shirazi, E. Pearson, L. Walker, M. Bird, C. Oliver, J. Waite
Summary: Assessing depression in individuals with severe to profound intellectual disability is challenging due to the inability to report internal states, but behaviors captured by standard diagnostic schemes show a relationship with depression. Challenging behaviors are associated with depression, suggesting caution in labeling them as 'depressive equivalents' without controlling for potential confounds and bias.
JOURNAL OF INTELLECTUAL DISABILITY RESEARCH
(2021)
