The prevalence of prenatal sonographic findings in postnatal diagnostic exome sequencing performed for neurocognitive phenotypes: A cohort study

Abstract

Objective: Prenatal exome sequencing (ES) is currently indicated for fetal malformations. Some neurocognitive genetic disorders may not have a prenatal phenotype. We assessed the prevalence of prenatally detectable phenotypes among patients with neurocognitive syndromes diagnosed postnatally by ES. Methods:The medical files of a cohort of 138 patients diagnosed postnatally with a neurocognitive disorder using ES were reviewed for prenatal sonographic data. The Online Mendelian Inheritance in Man (OMIM) database was searched for prenatally detectable phenotypes for all genes identified.Results: Prenatal imaging data were available for 122 cases. Of these, 29 (23.75%) had fetal structural abnormalities and another 29 had other ultrasound abnormalities (fetal growth restriction, polyhydramnios, elevated nuchal translucency). In 30 patients, structural aberrations that were not diagnosed prenatally were detected at birth; in 21 (17.2%), the abnormalities could theoretically be detected prenatally by third-trimester/targeted scans. According to OMIM, 55.9% of the diagnosed genes were not associated with structural anomalies.Conclusions: Most patients (52.5%) with postnatally diagnosed neurocognitive disorders did not have prenatal sonographic findings indicating prenatal ES should be considered. The prevalence of specific prenatal phenotypes such as fetal growth restriction and polyhydramnios in our cohort suggests that additional prenatal findings should be assessed as possible indications for prenatal ES.

A Rare De Novo Mutation in the TRIM8 Gene in a 17-Year-Old Boy with Steroid-Resistant Nephrotic Syndrome: Case Report

“…In the presented case, the c.1200C>G variant of the TRIM8 gene was described in a patient with NS, seizures, delayed speech and language development, failure to thrive, short stature, and immunodeficiency disorder. The mutation was excluded in proband's parents [20]. According to the OMIM (Online Mendelian Inheritance in Man; https://omim.org/about, accessed on 18 April 2024) database, expression of the pathogenic variants of the TRIM8 gene (mainly nonsense and frameshift variants) lead to a focal segmental glomerulosclerosis and neurodevelopmental syndrome in an autosomal dominant inheritance pattern (MIM#619428).…”

A Prenatal Presentation of CDK13-Related Disorder with a Novel Pathogenic Variant

“…In a retrospective study by Sukenik-Halevy et al [ 9 ] prenatal imaging data were reviewed in 122 patients with a postnatal diagnosis of a neurocognitive disorder. In two patients diagnosed with CDK13-related disorder, there were no findings in prenatal imaging and both had a normal NT measurement.…”

Prenatal ultrasound findings associated with PIGW variants: One more piece in the FRYNS syndrome puzzle? PIGW‐related prenatal findings

“…To further investigate the likely causative role of PIGW variants, we compared the prenatal findings associated with PIGW with those reported for the others PIG/PGAPs . (Table 2) 13–32 , 36–51 . Based on selected articles, phenotypic comparison is possible mostly for PIGW , PIGN , PIGV and PIGA , for which the description of prenatal manifestations is available.…”