EP15.01: First prenatal diagnosis of Myhre syndrome

Myhre syndrome, caused by heterozygous mutation in the SMAD4 gene on chromosome 18q21, is a rare disorder characterised by mental retardation, dysmorphic facial features, typical skeletal anomalies and cardiovascular defects. Currently, 60 cases were reported. Although congenital features such as SGA and short long bones are common, no prenatal diagnosis was reported. We present a 36-year-old patient, gravida 3 para 2 with no remarkable personal or familial medical history. Nuchal translucency was 3.1 mm, therefore chorionic vilous sampling was performed revealing normal chromosomal microarray result (CMA), arr(1-22)x2,(XY)x1. Sequential anatomical scans dempnstrated sub-cutaneous tissues, abnormal skull shape with indentation of the fronto-temporal bones, dysmorphic facial features including a wide fronto-nasal angle, short long bones (<1st percentile), small hand and fingers, mild ventriculomegaly and a short corpus callosum. Computerised tomography and magnetic resonance imaging confirmed the sonographic findings. Whole-exome sequencing revealed the following variant in the SMAD4 gene: SMAD4:c.1498A>G;p.Ile500Val (het, de novo) NM_005359.5, rs281875322. Following a thorough genetic counselling interpeting the variant in the SMAD4 gene and the ultrasonographic findings as Myhre syndrome, at 35 weeks of gestation the parents elected termination of pregnancy. Post-mortem assessment of the abortus revealed typical facial dysmorphism as demonstrated by 2-D and 3-D ultrasound. 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.