EP18.02: Prenatal diagnosis of a rare case of Meckel Gruber syndrome type 3 using first trimester ultrasound and exome sequencing

Meckel Gruber syndrome (MGS) is an autosomal recessive pre- or perinatal lethal malformation syndrome caused by primary ciliary dysfunction during early embryogenesis and characterised by classical triad of renal cystic dysplasia and occipital encephalocele and postaxial polydactyly. Here we report a case of MGS detected in first trimester ultrasound without polydactyly. A 23-year-old woman G2P0010, previous pregnancy was interrupted because of polycystic kidney disease at 14 weeks without genetic confirmation. She was referred to our centre due to only suspected brain abnormalities in first trimester ultrasound screening. Level 2 ultrasound at 12 weeks revealed encephalocele, bilateral renal cystic dysplasia without polydactyly. CVS was performed with normal CMA results. Trios whole exome sequencing (WES) showed that fetus had compound heterozygous mutations NM_001142301.1: c.395G>A (p.Arg132His) and NM_001142301.1: c.1332+5G>A in TMEM67 gene that inherited from each parent. This finding was consistent with clinical features of MGS type 3 (OMIM 607361). This case highlights the ability to detect both crucial and subtle anomalies in the first trimester using targeted ultrasound. Thanks to a high recurrence risk of 25%, comprehensive genetic counselling is essential for planning care in future pregnancies. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.