Characterisation of the clinical phenotype in Phelan-McDermid syndrome

Journal of Neurodevelopmental Disorders

Patricia Hernández-Jusdado¹  Antonia San José-Cáceres²  Javier González-Peñas³  Alicia García-Alcón⁴  Mara Parellada-Redondo⁴  Mónica Burdeus-Olavarrieta⁵ 

[1] Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Calle Ibiza 43, 28009, Madrid, Spain;Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Calle Ibiza 43, 28009, Madrid, Spain;IiSGM, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain;Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Calle Ibiza 43, 28009, Madrid, Spain;IiSGM, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain;CIBERSAM, Centro de Investigación Biomédica en Red Salud Mental, Madrid, Spain;Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Calle Ibiza 43, 28009, Madrid, Spain;IiSGM, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain;School of Medicine, Universidad Complutense, Madrid, Spain;Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Calle Ibiza 43, 28009, Madrid, Spain;IiSGM, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain;School of Psychology, Universidad Autónoma, Madrid, Spain;

关键词: Phelan-McDermid syndrome;    22q13 deletion syndrome;    SHANK3;    Intellectual disability;    Autism;   

DOI  :  10.1186/s11689-021-09370-5

来源: Springer

【 摘 要 】

BackgroundPhelan-McDermid syndrome (PMS) is a rare genetic disorder compromising the 22q13 terminal region and affecting SHANK3, a gene crucial to the neurobehavioural phenotype and strongly linked to autism (ASD) and intellectual disability (ID). The condition is characterised by global developmental delay, ID, speech impairments, hypotonia and autistic behaviours, although its presentation and symptom severity vary widely. In this study, we provide a thorough description of the behavioural profile in PMS and explore differences related to deletion size and language ability.MethodsWe used standard clinical assessment instruments to measure altered behaviour, adaptive skills and autistic symptomatology in sixty participants with PMS (30 females, median age 8.5 years, SD=7.1). We recorded background information and other clinical manifestations and explored associations with deletion size. We performed descriptive and inferential analyses for group comparison.ResultsWe found delayed gross and fine motor development, delayed and impaired language (~70% of participants non or minimally verbal), ID of different degrees and adaptive functioning ranging from severe to borderline impairment. Approximately 40% of participants experienced developmental regression, and half of those regained skills. Autistic symptoms were frequent and variable in severity, with a median ADOS-2 CSS score of 6 for every domain. Sensory processing anomalies, hyperactivity, attentional problems and medical comorbidities were commonplace. The degree of language and motor development appeared to be associated with deletion size.ConclusionsThis study adds to previous research on the clinical descriptions of PMS and supports results suggesting wide variability of symptom severity and its association with deletion size. It makes the case for suitable psychotherapeutic and pharmacological approaches, for longitudinal studies to strengthen our understanding of possible clinical courses and for more precise genomic analysis.

【 授权许可】

CC BY