Microcephaly
Gene: DDX11
PMID 30216658 reviews 12 individuals reported to date: severe microcephaly with prenatal onset was identified in all patients, and severe pre- and postnatal growth restriction was observed in 11 of 11 patients. All 12 patients had sensorineural hearing loss, with 10 of 10 having cochlear hypoplasia or functional abnormalities; 1 patient had a posterior labyrinthine anomaly. In all 4 patients who had brain imaging, abnormalities were identified. Some patients had other structural anomalies, including cardiac defects (5/12), recurrent infections (4/9), and skin pigmentation changes (6/12). Craniofacial features included a depressed nasal bridge with a broad nasal tip and overhanging columella. Elevated induced chromosome breakage was observed in 6 of 8 reported patients. Cohesin defects (premature chromatid separation and premature centromere division) were consistent in most metaphases among the patients examined.Created: 14 Apr 2021, 11:41 a.m. | Last Modified: 14 Apr 2021, 11:41 a.m.
Panel Version: 1.1
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Warsaw breakage syndrome, MIM# 613398; MONDO:0013252
Publications
The cardinal clinical features observed in Warsaw breakage syndrome (WABS) patients include severe pre- and post-natal growth retardation, microcephaly, sensorineural hearing loss, cochlear anomalies, facial dysmorphia and sister chromatid cohesion defects (PMID: 31824187).
A male patient with biallelic DDX11 variants (splice site and in-frame deletion) presented with several congenital abnormalities, including microcephaly, facial dysmorphy, high arched palate, coloboma of the right optic disc, deafness, small ventricular septal defect, bilateral clinodactyly of the fifth fingers, syndactyly of the second and third toes, cutis marmorata, and one hypo- and three hyperpigmented patches on the skin. Authors proposed to name the syndrome associated with defective DDX11 “Warsaw breakage syndrome” (WABS) (PMID: 20137776).
Three siblings carrying a biallelic DDX11 missense variant with clinical presentation of WABS: ID, growth retardation, and severe congenital abnormalities including microcephaly, facial dysmorphism, deafness due to cochlear abnormalities (in two of the sibs), and cardiac malformations (in one of the sibs) (PMID: 23033317).
Sources: LiteratureCreated: 2 Sep 2020, 2:15 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Warsaw breakage syndrome, MIM#613398
Publications
Phenotypes for gene: DDX11 were changed from Warsaw breakage syndrome, MIM#613398 to Warsaw breakage syndrome, MIM# 613398; MONDO:0013252
Publications for gene: DDX11 were set to 31824187; 20137776; 23033317; 30216658
Publications for gene: DDX11 were set to PMID: 31824187; 20137776; 23033317.
Gene: ddx11 has been classified as Green List (High Evidence).
Gene: ddx11 has been classified as Green List (High Evidence).
gene: DDX11 was added gene: DDX11 was added to Microcephaly. Sources: Literature Mode of inheritance for gene: DDX11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DDX11 were set to PMID: 31824187; 20137776; 23033317. Phenotypes for gene: DDX11 were set to Warsaw breakage syndrome, MIM#613398 Penetrance for gene: DDX11 were set to Complete Review for gene: DDX11 was set to GREEN