Prenatal phenotype of Kabuki syndrome: A case series and literature review.

OBJECTIVES: Kabuki syndrome (KS) is a genetic disorder characterized by intellectual disability, facial dysmorphism and congenital anomalies. We aim to investigate the prenatal features of fetuses with KS and to provide a comprehensive review of the literature on prenatal sonographic abnormalities associated with KS. METHODS: We retrospectively reviewed the prenatal ultrasound findings of all mothers of children with molecularly confirmed KS in Hong Kong, between 1991 and 2019. We also performed systematic review of the literature to identify studies on the prenatal findings in KS. RESULTS: We identified 11 cases with KS with detectable fetal ultrasound findings ranging from no detectable abnormalities to a variety of non-specific findings including increased nuchal translucency, pleural effusion, cardiac anomalies, renal anomalies, intrauterine growth restriction, polyhydramnios, oligohydramnios and single umbilical artery. In combining our cases with the 77 cases published, 42 (50.6%) of them had more than one abnormal antenatal ultrasound finding. The most frequent ultrasound features observed were cardiac anomalies (49.4%), followed by polyhydramnios (28.9%), genitourinary anomalies (26.5%), single umbilical artery (15.7%), intrauterine growth restriction (14.5%) and hydrops fetalis/pleural effusion/ascites (12.0%). CONCLUSIONS: These cases demonstrate the prenatal phenotypic heterogeneity associated with KS. Although the ultrasound abnormalities are non-specific, KS should be considered in the differential diagnosis when these fetal findings following normal microarray analysis/karyotyping.

Further expanding the clinical phenotype in Bainbridge-Ropers syndrome and dissecting genotype-phenotype correlation in the ASXL3 mutational cluster regions.

Bainbridge-Ropers syndrome (BRPS) [OMIM#615485] is a neurodevelopmental disorder, characterized by delayed psychomotor development with generalized hypotonia, intellectual disability with poor or absent speech, feeding difficulties, growth failure, specific craniofacial and minor skeletal features. It was firstly reported in 2013 by Bainbridge et al., who observed a group of individuals sharing overlapping features with Bohring-Opitz syndrome which were caused by pathogenic variant in ASXL1, who indeed carried truncating mutations in ASXL3. To date, 33 cases were described in the literature. BRPS is caused by loss-of-function mutations in ASXL3 which are mostly located in two mutational cluster regions (MCR). The exact molecular mechanism of these mutations resulting in the disease phenotype is still uncertain due to the observation of LOF mutations in healthy population. Here, we report four individuals with BRPS carrying de novo LOF mutations in ASXL3, comparing and summarizing the clinical phenotype of all BRPS reported so far. Furthermore, we try to dissect the genotype-phenotype correlation among the two well reported MCRs in all BRPS from the literature.