DDX3X Syndrome Behavioral Manifestations with Particular Emphasis on Psycho-Pathological Symptoms-A Review

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2023 Nov 25

PMID 38002045

Authors

Urszula Stefaniak

Roksana Malak

Ada Kaczmarek

Wlodzimierz Samborski

Ewa Mojs

Affiliations

Soon will be listed here.

Abstract

(1) Background: Identification of typical behavioral manifestations in patients with DEAD-Box Helicase 3 X-linked gene () variants plays a crucial role in accurately diagnosing and managing the syndrome. The objective of this paper was to carry out a review of medical and public databases and assess the behavioral features of the DDX3X syndrome (DDX3X), with a particular focus on psycho-pathological symptoms. (2) Methods: An extensive computerized search was conducted in various databases, including PubMed, Medline Complete, Science Direct, Scopus, and Web of Science. Specific keywords and Medical Subject Headings were used to ensure the inclusion of relevant studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to assess the methodological quality of the manuscripts. (3) Results: Only nine papers out of the 272 assessed met the inclusion criteria. These articles revealed various psycho-pathological manifestations in patients with the DDX3X syndrome. Intellectual disability (ID) or developmental disability (DD), speech delay, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), generalized anxiety disorder (GAD), self-injurious behaviors (SIBs), sensory symptoms and sleep disturbance were demonstrated to be the most common psycho-pathological behavior manifestations. (4) Conclusions: Patients with the DDX3X syndrome manifest a wide spectrum of psycho-pathological symptoms. A comprehensive investigation of these symptoms in patients is essential for early diagnosis and effective therapy.

Citing Articles

First Diagnostic Questionnaire for Assessing Patients' Social Functioning: Comprehensive DDX3X Syndrome Patient Profile.

Stefaniak-Preis U, Kaczmarek A, Andrusiewicz M, Roszak M, Trzeszczynska N, Samborski W J Clin Med. 2025; 13(24.

PMID: 39768765 PMC: 11676840. DOI: 10.3390/jcm13247842.

References

Amadori E, Scala M, Cereda G, Vari M, Marchese F, Di Pisa V . Targeted re-sequencing for early diagnosis of genetic causes of childhood epilepsy: the Italian experience from the 'beyond epilepsy' project. Ital J Pediatr. 2020; 46(1):92. PMC: 7339579. DOI: 10.1186/s13052-020-00860-1. View

Latreche K, Kojovic N, Franchini M, Schaer M . Attention to Face as a Predictor of Developmental Change and Treatment Outcome in Young Children with Autism Spectrum Disorder. Biomedicines. 2021; 9(8). PMC: 8392329. DOI: 10.3390/biomedicines9080942. View

Scala M, Nishikawa M, Ito H, Tabata H, Khan T, Accogli A . Variant-specific changes in RAC3 function disrupt corticogenesis in neurodevelopmental phenotypes. Brain. 2022; 145(9):3308-3327. PMC: 9473360. DOI: 10.1093/brain/awac106. View

Nicola P, Blackburn P, Rasmussen K, Bertsch N, Klee E, Hasadsri L . De novo DDX3X missense variants in males appear viable and contribute to syndromic intellectual disability. Am J Med Genet A. 2019; 179(4):570-578. DOI: 10.1002/ajmg.a.61061. View

Scala M, Mojarrad M, Riazuddin S, Brigatti K, Ammous Z, Cohen J . RSRC1 loss-of-function variants cause mild to moderate autosomal recessive intellectual disability. Brain. 2020; 143(4):e31. PMC: 7174030. DOI: 10.1093/brain/awaa070. View

Scala M, Torella A, Severino M, Morana G, Castello R, Accogli A . Three de novo DDX3X variants associated with distinctive brain developmental abnormalities and brain tumor in intellectually disabled females. Eur J Hum Genet. 2019; 27(8):1254-1259. PMC: 6777618. DOI: 10.1038/s41431-019-0392-7. View

Lennox A, Hoye M, Jiang R, Johnson-Kerner B, Suit L, Venkataramanan S . Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development. Neuron. 2020; 106(3):404-420.e8. PMC: 7331285. DOI: 10.1016/j.neuron.2020.01.042. View

Hu L, Xin X, Lin S, Luo M, Chen J, Qiu H . A child with a novel DDX3X variant mimicking cerebral palsy: a case report. Ital J Pediatr. 2020; 46(1):88. PMC: 7325255. DOI: 10.1186/s13052-020-00850-3. View

Dai Y, Yang Z, Guo J, Li H, Gong J, Xie Y . Expansion of Clinical and Genetic Spectrum of Neurodevelopmental Disorder in 23 Chinese Patients. Front Mol Neurosci. 2022; 15:793001. PMC: 8981727. DOI: 10.3389/fnmol.2022.793001. View

10.

Vitobello A, Mazel B, Lelianova V, Zangrandi A, Petitto E, Suckling J . ADGRL1 haploinsufficiency causes a variable spectrum of neurodevelopmental disorders in humans and alters synaptic activity and behavior in a mouse model. Am J Hum Genet. 2022; 109(8):1436-1457. PMC: 9388395. DOI: 10.1016/j.ajhg.2022.06.011. View

11.

Kellaris G, Khan K, Baig S, Tsai I, Zamora F, Ruggieri P . A hypomorphic inherited pathogenic variant in DDX3X causes male intellectual disability with additional neurodevelopmental and neurodegenerative features. Hum Genomics. 2018; 12(1):11. PMC: 5831694. DOI: 10.1186/s40246-018-0141-y. View

12.

Beal B, Hayes I, McGaughran J, Amor D, Miteff C, Jackson V . Expansion of phenotype of DDX3X syndrome: six new cases. Clin Dysmorphol. 2019; 28(4):169-174. DOI: 10.1097/MCD.0000000000000289. View

13.

Gillentine M, Wang T, Eichler E . Estimating the Prevalence of De Novo Monogenic Neurodevelopmental Disorders from Large Cohort Studies. Biomedicines. 2022; 10(11). PMC: 9687899. DOI: 10.3390/biomedicines10112865. View

14.

Levy T, Siper P, Lerman B, Halpern D, Zweifach J, Belani P . DDX3X Syndrome: Summary of Findings and Recommendations for Evaluation and Care. Pediatr Neurol. 2022; 138:87-94. DOI: 10.1016/j.pediatrneurol.2022.10.009. View

15.

Schroder M . Viruses and the human DEAD-box helicase DDX3: inhibition or exploitation?. Biochem Soc Trans. 2011; 39(2):679-83. DOI: 10.1042/BST0390679. View

16.

Wang X, Posey J, Rosenfeld J, Bacino C, Scaglia F, Immken L . Phenotypic expansion in - a common cause of intellectual disability in females. Ann Clin Transl Neurol. 2018; 5(10):1277-1285. PMC: 6186933. DOI: 10.1002/acn3.622. View

17.

Mo J, Liang H, Su C, Li P, Chen J, Zhang B . DDX3X: structure, physiologic functions and cancer. Mol Cancer. 2021; 20(1):38. PMC: 7903766. DOI: 10.1186/s12943-021-01325-7. View

18.

Gunderson J, Worthley E, Byiers B, Symons F, Wolff J . Self and caregiver report measurement of sensory features in autism spectrum disorder: a systematic review of psychometric properties. J Neurodev Disord. 2023; 15(1):5. PMC: 9875408. DOI: 10.1186/s11689-022-09473-7. View

19.

Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev. 2021; 10(1):89. PMC: 8008539. DOI: 10.1186/s13643-021-01626-4. View

20.

Levit-Binnun N, Davidovitch M, Golland Y . Sensory and motor secondary symptoms as indicators of brain vulnerability. J Neurodev Disord. 2013; 5(1):26. PMC: 3849186. DOI: 10.1186/1866-1955-5-26. View