Genetic architecture of childhood speech disorder: a review

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(5), P. 1281 - 1292

Published: Feb. 16, 2024

Abstract Severe speech disorders lead to poor literacy, reduced academic attainment and negative psychosocial outcomes. As early as the 1950s, familial nature of was recognized, implying a genetic basis; but molecular basis remained unknown. In 2001, investigation large three generational family with severe disorder, known childhood apraxia (CAS), revealed first causative gene; FOXP2 . A long hiatus then followed for CAS candidate genes, in past years, analysis cohorts ascertained have over 30 genes. total 36 pathogenic variants been identified from 122 cases across 3 this nascent field. All genes coding regions date, no apparent benefit at stage WGS WES identifying monogenic conditions associated CAS. Hence current findings suggest remarkable one children variant that explains their CAS, significant heterogeneity emerging. Around half are currently supported by medium (6 genes) strong (9 evidence supporting association between gene Despite heterogeneity; many implicated proteins functionally converge on pathways involved chromatin modification or transcriptional regulation, opening door precision diagnosis therapies. Most new previously described neurodevelopmental include intellectual disability, autism epilepsy; broadening phenotypic spectrum distinctly milder presentation defined primary disorder setting normal intellect. Insights into bases severe, rare yet translate understanding heritability more common, typically forms language impairment such stuttering phonological disorder. These likely follow complex inheritance polygenic contributions cases, rather than patterns underly one-third patients Clinical testing should now be implemented individuals given its high diagnostic rate, which parallels other where is already standard care. The shared mechanisms discovery highlight potential targets future

Language: Английский

---

Expanding the phenotype of Kleefstra syndrome: speech, language and cognition in 103 individuals

Journal of Medical Genetics, Journal Year: 2024, Volume and Issue: 61(6), P. 578 - 585

Published: Jan. 30, 2024

Objectives Speech and language impairments are core features of the neurodevelopmental genetic condition Kleefstra syndrome. Communication has not been systematically examined to guide intervention recommendations. We define speech, cognitive phenotypic spectrum in a large cohort individuals with Method 103 syndrome (40 males, median age 9.5 years, range 1–43 years) pathogenic variants (52 9q34.3 deletions, 50 intragenic variants, 1 balanced translocation) were included. Speech, non-verbal communication assessed. Cognitive, health data obtained. Results The ranged from average intelligence (12/79, 15%) severe intellectual disability 15%). Language ability also (10/90, 11%) (53/90, 59%). disorders occurred 48/49 (98%) verbal even alongside cognition. Developmental regression 11/80 (14%) across motor, psychosocial domains. aids, such as sign speech-generating devices, crucial for 61/103 (59%) including those who minimally verbal, had speech disorder or following regression. Conclusions profile is broad, ranging impairment ability. Genotype do explain variability. Early access aids may improve quality life.

Language: Английский

---

Editorial: Characterizing the neurobehavioral phenotype of mendelian disorders of epigenetic machinery

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 5, 2023

EDITORIAL article Front. Genet., 05 December 2023Sec. Genetics of Common and Rare Diseases Volume 14 - 2023 | https://doi.org/10.3389/fgene.2023.1338078

Language: Английский

---

Expanding the Neuropsychological Phenotype of KAT6B Disorders: Overlapping Features with KAT6A Syndrome

Journal of Autism and Developmental Disorders, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 17, 2024

Language: Английский

---