أعرض في EDS

The clinical and genetic spectrum of paediatric speech and language disorders in 52,143 individuals.

التفاصيل البيبلوغرافية
العنوان: The clinical and genetic spectrum of paediatric speech and language disorders in 52,143 individuals.
المؤلفون: Magielski J; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, 19146, USA., Ruggiero SM; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA., Xian J; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, 19146, USA., Parthasarathy S; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, 19146, USA., Galer P; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, 19146, USA.; Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA., Ganesan S; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, 19146, USA., Back A; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA., McKee J; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, 19146, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., McSalley I; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, 19146, USA., Gonzalez AK; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, 19146, USA., Morgan A; Murdoch Children's Research Institute, Parkville 3052, Australia.; Department of Audiology and Speech Pathology, University of Melbourne, Parkville 3052, Australia., Donaher J; Center for Childhood Communication, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA., Helbig I; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, 19146, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
المصدر: MedRxiv : the preprint server for health sciences [medRxiv] 2024 Apr 23. Date of Electronic Publication: 2024 Apr 23.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE
مستخلص: Speech and language disorders are known to have a substantial genetic contribution. Although frequently examined as components of other conditions, research on the genetic basis of linguistic differences as separate phenotypic subgroups has been limited so far. Here, we performed an in-depth characterization of speech and language disorders in 52,143 individuals, reconstructing clinical histories using a large-scale data mining approach of the Electronic Medical Records (EMR) from an entire large paediatric healthcare network. The reported frequency of these disorders was the highest between 2 and 5 years old and spanned a spectrum of twenty-six broad speech and language diagnoses. We used Natural Language Processing to assess to which degree clinical diagnosis in full-text notes were reflected in ICD-10 diagnosis codes. We found that aphasia and speech apraxia could be easily retrieved through ICD-10 diagnosis codes, while stuttering as a speech phenotype was only coded in 12% of individuals through appropriate ICD-10 codes. We found significant comorbidity of speech and language disorders in neurodevelopmental conditions (30.31%) and to a lesser degree with epilepsies (6.07%) and movement disorders (2.05%). The most common genetic disorders retrievable in our EMR analysis were STXBP1 ( n =21), PTEN ( n =20), and CACNA1A ( n =18). When assessing associations of genetic diagnoses with specific linguistic phenotypes, we observed associations of STXBP1 and aphasia ( P =8.57 × 10 -7 , CI=18.62-130.39) and MYO7A with speech and language development delay due to hearing loss ( P =1.24 × 10 -5 , CI=17.46-Inf). Finally, in a sub-cohort of 726 individuals with whole exome sequencing data, we identified an enrichment of rare variants in synaptic protein and neuronal receptor pathways and associations of UQCRC1 with expressive aphasia and WASHC4 with abnormality of speech or vocalization. In summary, our study outlines the landscape of paediatric speech and language disorders, confirming the phenotypic complexity of linguistic traits and novel genotype-phenotype associations. Subgroups of paediatric speech and language disorders differ significantly with respect to the composition of monogenic aetiologies.
Competing Interests: Competing interests The authors report no competing interests.
معلومات مُعتمدة: K02 NS112600 United States NS NINDS NIH HHS
فهرسة مساهمة: Keywords: Human Phenotype Ontology; electronic medical records; genetics; language disorder; speech disorder
تواريخ الأحداث: Date Created: 20240507 Latest Revision: 20240513
رمز التحديث: 20240513
مُعرف محوري في PubMed: PMC11071575
DOI: 10.1101/2024.04.23.24306192
PMID: 38712155
قاعدة البيانات: MEDLINE
الوصف
DOI:10.1101/2024.04.23.24306192