DDX3X Syndrome: Summary of Findings and Recommendations for Evaluation and Care

Levy, Tess; Siper, Paige M.; Lerman, Bonnie; Halpern, Danielle; Zweifach, Jessica; Belani, Puneet; Thurm, Audrey; Kleefstra, Tjitske; Berry‐Kravis, Elizabeth; Buxbaum, Joseph D.; Grice, Dorothy E.

doi:10.1016/j.pediatrneurol.2022.10.009

Cited by 12 publications

(52 citation statements)

References 13 publications

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“…Table 2 also shows the clinical information of 200 previously published patients [3][4][5][6]10 with confirmed genetic variants in DDX3X and the total frequencies resulting from the sum of the clinical features of both groups.…”

Section: Clinical Features Of Reported Patientsmentioning

confidence: 99%

“…3 Since then, more than 200 patients have been published in several articles [4][5][6][7] and case reports. 8,9 In 2023, Levy et al, 10 grouped most of the reported patients and proposed recommendations for evaluation and care of patients with DDX3X-NDD. The main clinical features of this Members of Spanish OverGrowth Registry Initiative are given in the acknowledgments.…”

Section: Introductionmentioning

confidence: 99%

“…However, DDX3X-NDD is extremely variable and other clinical features have also been observed in patients, such as microcephaly, behavioral problems, hearing loss and different dysmorphic facial features. 10 DDX3X-NDD is caused by pathogenic variants in the DEAD-box helicase 3, X-linked (DDX3X) gene located at chromosome Xp11.4. 3 DDX3X encoded for a 662-amino acid polypeptide organized into two domains: helicase ATP-binding and helicase C-terminal 11 and three motifs: the nuclear export signal, the Q-motif and the DEAD box (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…15 To date, reported pathogenic or likely pathogenic variants in DDX3X-NDD patients comprise missense, nonsense, frameshift, splice site and in-frame deletion variants. [3][4][5][6][7]10 Two patients with clinical features overlapping with DDX3X-NDD have also been reported with CNVs encompassing DDX3X. 16 Patients with missense variants presented with an apparently more severe phenotype than those with likely gene-disrupting variants.…”

Section: Introductionmentioning

confidence: 99%

“…The main clinical features of this condition include developmental delay, ID, hypotonia, abnormal brain MRI, and gait and sleep disturbance, among others. However, DDX3X‐NDD is extremely variable and other clinical features have also been observed in patients, such as microcephaly, behavioral problems, hearing loss and different dysmorphic facial features 10 …”

Section: Introductionmentioning

confidence: 99%

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Genetic and phenotypic findings in 34 novel Spanish patients with DDX3X neurodevelopmental disorder

Parra,

Pascual,

Cazalla

et al. 2023

Clinical Genetics

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DDX3X is a multifunctional ATP‐dependent RNA helicase involved in several processes of RNA metabolism and in other biological pathways such as cell cycle control, innate immunity, apoptosis and tumorigenesis. Variants in DDX3X have been associated with a developmental disorder named intellectual developmental disorder, X‐linked syndromic, Snijders Blok type (MRXSSB, MIM #300958) or DDX3X neurodevelopmental disorder (DDX3X‐NDD). DDX3X‐NDD is mainly characterized by intellectual disability, brain abnormalities, hypotonia and behavioral problems. Other common findings include gastrointestinal abnormalities, abnormal gait, speech delay and microcephaly. DDX3X‐NDD is predominantly found in females who carry de novo variants in DDX3X. However, hemizygous pathogenic DDX3X variants have been also found in males who inherited their variants from unaffected mothers. To date, more than 200 patients have been reported in the literature. Here, we describe 34 new patients with a variant in DDX3X and reviewed 200 additional patients previously reported in the literature. This article describes 34 additional patients to those already reported, contributing with 25 novel variants and a deep phenotypic characterization. A clinical review of our cohort of DDX3X‐NDD patients is performed comparing them to those previously published.

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Section: Clinical Features Of Reported Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Genetic and phenotypic findings in 34 novel Spanish patients with DDX3X neurodevelopmental disorder

Parra,

Pascual,

Cazalla

et al. 2023

Clinical Genetics

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Speech and language in DDX3X‐neurodevelopmental disorder: A call for early augmentative and alternative communication intervention

Forbes,

Morison,

Lelik

et al. 2024

American J of Med Genetics Pt B

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Pathogenic variants in DDX3X are associated with neurodevelopmental disorders. Communication impairments are commonly reported, yet specific speech and language diagnoses have not been delineated, preventing prognostic counseling and targeted therapies. Here, we characterized speech and language in 38 female individuals, aged 1.69–24.34 years, with pathogenic and likely pathogenic DDX3X variants (missense, n = 13; nonsense, n = 12; frameshift, n = 7; splice site, n = 3; synonymous, n = 2; deletion, n = 1). Standardized speech, language, motor, social, and adaptive behavior assessments were administered. All participants had gross motor deficits in infancy (34/34), and fine motor deficits were common throughout childhood (94%; 32/34). Intellectual disability was reported in 86% (24/28) of participants over 4 years of age. Expressive, receptive, and social communication skills were, on average, severely impaired. However, receptive language was significantly stronger than expressive language ability. Over half of the assessed participants were minimally verbal (66%; 22/33; range = 2 years 2 months–24 years 4 months; mean = 8 years; SD = 6 years) and augmented speech with sign language, gestures, or digital devices. A quarter of the cohort had childhood apraxia of speech (25%; 9/36). Despite speech and language impairments, social motivation was a relevant strength. Many participants used augmentative and alternative communication (AAC), underscoring the need for early, tailored, and comprehensive AAC intervention.

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Assessing motor development and function in mouse models of neurodevelopmental disorders

Dierdorff,

Garcia-Forn,

von Mueffling

et al. 2024

Methods in Cell Biology

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DDX3X Syndrome: Summary of Findings and Recommendations for Evaluation and Care

Cited by 12 publications

References 13 publications

Genetic and phenotypic findings in 34 novel Spanish patients with DDX3X neurodevelopmental disorder

Genetic and phenotypic findings in 34 novel Spanish patients with DDX3X neurodevelopmental disorder

Speech and language in DDX3X‐neurodevelopmental disorder: A call for early augmentative and alternative communication intervention

Assessing motor development and function in mouse models of neurodevelopmental disorders

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