Background. Heterozygous pathogenic variants in the DDX3X gene account for 1–3% of females with intellectual and developmental disabilities (IDD). The clinical presentation is variable, including a wide range of neurological and behavioral deficits and structural defects of the brain. Approximately 52% of affected females remain nonverbal after five years of age. Case presentation: We report a 7 year old nonverbal female with a likely novel de novo pathogenic heterozygous variant in the DDX3X gene affecting the non-canonical splice-site in the intron 1 (NM_001356:c.45+12G>A). The patient presents with features typical for the DDX3X phenotype, such as: movement disorders, behavioral problems, a diagnosis of autism spectrum disorder (ASD), and some other features uncommon for DDX3X such as: muscle hypertonia and spinal asymmetry evaluated through the scoliometer. Conclusions. Due to its rare occurrence, the clinical picture of DDX3X syndrome is yet to be fully determined. So far, behavioral disorders, including those from ASD, and neurological abnormalities seem to be the dominant features of this disorder.

(1) Background: Identification of typical behavioral manifestations in patients with DEAD-Box Helicase 3 X-linked gene (DDX3X) 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.

Background/Objectives: DDX3X syndrome is often misdiagnosed as autism spectrum disorder (ASD, Rett Syndrome, and Dandy–Walker Syndrome). Precise phenotyping is needed with reference to neurodevelopmental diagnosis. Observation of behavior and communication in parents with DDX3X syndrome in the USA, France, and Poland; conversations with the parents of patients; and rudimentary information in evidence-based medical articles prompted us to identify differences in communication, play, and social interaction between children with ASD only, those with both ASD and DDX3X, and those with DDX3X only. Methods: As diagnostic tool for DDX3X patients, we created a questionnaire divided into four sections: medical, social, play, and communication. Results: The results showed inconsistent diagnoses in different countries where children could have been diagnosed with DDX3X. In a comparative analysis, individuals with DDX3X exhibited greater social skills than individuals with ASD. Furthermore, those with DDX3X demonstrated higher levels of social functioning compared to children with ASD. Therefore, parents of children recently diagnosed with ASD or similar conditions are encouraged to complete a survey to determine if their child is likely to have features of DDX3X syndrome. Conclusion: Identification of early behavioral markers that differentiate children with ASD and those with DDX3X could lead to the earliest opportunity for identification and intervention, and can significantly impact developmental trajectories, leading to better long-term outcomes.

INPLASY202390087 DDX3X SYNDROME BEHAVIORAL MANIFESTATIONS WITH PARTICULAR EMPHASIS ON PSYCHO-PATHOLOGICAL SYMPTOMS- A SYSTEMATIC REVIEW Keywords: DDX3X Syndrome. Intellectual Disability. Developmen…