VP16.11: FACTO syndrome

Abstract

Objectives: Coffin-Siris syndrome (CSS) is a rare AD disorder caused by mutations in genes of BAF chromatin-remodelling complex, characterised by aplasia/hypoplasia of the distal phalanx/nail of the fifth digit, intellectual disability, distinctive facial features, hypotonia, hypertrichosis and sparse scalp hair. Rare prenatal manifestations of CSS have been reported. We describe prenatal manifestations detected in 3 fetuses with CSS. Methods: Retrospective review of prenatal and postnatal data of 3 patients referred for fetal anomalies. Results: Fetal anomalies included: increased nuchal translucency (2); early IUGR increasing in severity with pregnancy (3); macrocrania (2); callosal agenesis; cerebellar hypoplasia (3); cardiac anomalies (3); thoracic anomalies (3): lung hypoplasia (3); diaphragmatic agenesis (1); left diaphragmatic hernia (1); Polyhydramnios (3).Distal skeletal anomalies (2): flexion of all toes; adduction of first toes (1); short fifth digits (1); talipes equinovarus (1); scoliosis (1); multicystic dysplastic kidney (1); facial dysmorphism (1).Two families opted for comfort management, and postnatal explorations; both neonates died after a few hours. A pathogenic de novo variant of ARID 1 A was identified for each. Pathological exam was accepted for one and demonstrated evocative facial and digital features. X-rays diagnosed aplasia and hypoplasia of multiple phalanges (including the distal phalanges of fifth digits), 4 tarsal bone ossification centres (1) and 13 pairs of ribs (2). The third neonate with left diaphragmatic hernia is now 11 months old. Postnatal exam confirmed IUGR, microcephaly, and detected incomplete posterior palatal fissure, ungueal hypoplasia of the fifth digits, hypospadias, and inguinal hernia. A pathogenic de novo variant of SMARCA4 (c.2339A > G) was identified. Conclusions: CSS must be included in the differential diagnosis when fetus with IUGR present with midline CNS anomalies, right cardiac cavities predominance, and lung hypoplasia. A careful search for typical fifth digital hypoplasia and facial dysmorphism should be done.