EP18.19: Prenatal diagnosis of Cantú syndrome during the second trimester due to a novel ABCC9 pathogenic variant: a case report

Cantú syndrome is a rare disorder characterised by hypertrichosis, distinctive coarse facial features, enlarged heart and skeletal abnormalities. Developmental delays are common, but intellect is typically normal. Birth defects generally are macrosomia, macrocephaly, hypertrichosis, generalised edema, cardiac enlargement and wrinkled/loose skin. Although rare, the diagnosis is possible in case of suggestive clinical findings associated with a heterozygous pathogenic variant of the ABCC9 or KCNJ8 genes. The case: A 41-year-old G7P2A4 patient came to our centre at 16 weeks of pregnancy for a consultation on a prenatal test due to advanced maternal age. The ultrasound examination showed a fetal size assessment at mid to-low values and an echogenic fetal bowel. No other anomalies were noted. A week later, at 17 weeks the patient underwent amniocentesis resulting in an 46,XY normal fetal karyotype. Subsequently, the anatomy scan performed at 20th week of pregnancy, showed a femur length lower than 5th percentile and a Blake's pouch cyst. Exome sequencing was then carried out on the DNA extracted from amniotic fluid and revealed that the fetus was a heterozygous carrier of the NM_005691.4:c.1516A>C (p.Lys506Gln) variant in ABCC9. The variant was inferred to be de novo. The c.1516A>C is a novel and rare variant, not present the GnomAD 2.1 population database, and it is predicted to alter the structure/function of the ABCC9 coded protein (i.e. revel score=0.982). Accordingly, c.1516A>C variant was classified as likely pathogenic. After genetic counselling, the woman decided for termination of pregnancy. On post-mortem examination, the fetus was found with diffuse hypertrichosis. To our knowledge, this is the first clinical and molecular assessment of Cantu' syndrome in a prenatal case. The present findings expand the phenotypic spectrum of the Cantu' syndrome and indicate that a reduction of fetal biometrics at an early gestational age can be suggestive of this syndrome.