Rare syndromic craniosynostosis or isolated multisuture synostosis
Gene: DDX3X
Comment on list classification: Although there are five unrelated cases reported with DDX3X variants and likely craniosynostosis, only two are radiologically confirmed cases of craniosynostosis. Hence, this gene should be rated amber.Created: 20 Jul 2023, 11:13 a.m. | Last Modified: 20 Jul 2023, 11:13 a.m.
Panel Version: 4.118
A novel de novo missense variant was identified in the DDX3X gene (c.625C>G) by whole exome sequencing in a child with craniofacial dysmorphisms: brachycephaly and a flattened triangular-asymmetrical face characterized by micrognathia, mild hypertelorism, wide and prominent nose, short philtrum, thin lips and macroglossia (PMID:33789733).
Exome-sequencing identified three distinct de novo heterozygous variants in DDX3X: c.1511G>A; p.(Gly504Glu) (Patient 1), c.1436_1439delinsTCTC; p.(Asp479Arg480delinsValSer) (Patient 2), and c.641_643delTCA; p.(Ile214del) (Patient 3). The patients showed severe intellectual disability/developmental disorders, microcephaly, and dysmorphic features. Plagiocephaly was observed in Patient 1 and Patient 2 was diagnosed with sensorineural hearing loss and trigonocephaly. However, craniosynostosis was only radiologically confirmed in Patient 2 (PMID:30936465).
A de novo variant in DDX3X was identified in an additional patient with trigonocephaly, delay in speech acquisition and motor developmental delay: c.1616-2A>G (PMID:32530565).
Sources: LiteratureCreated: 20 Jul 2023, 11:09 a.m. | Last Modified: 20 Jul 2023, 11:15 a.m.
Panel Version: 4.118
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958; craniosynostosis, MONDO:0015469
Publications
Gene: ddx3x has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: DDX3X were changed from craniosynostosis, MONDO:0015469 to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958; craniosynostosis, MONDO:0015469
gene: DDX3X was added gene: DDX3X was added to Rare syndromic craniosynostosis or isolated multisuture synostosis. Sources: Literature Mode of inheritance for gene: DDX3X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: DDX3X were set to 30936465; 32530565; 33789733; 36980886 Phenotypes for gene: DDX3X were set to craniosynostosis, MONDO:0015469 Review for gene: DDX3X was set to AMBER