Prenatal diagnosis of Nager syndrome in the third trimester of pregnancy and anatomopathological correlation

Abstract

Nager syndrome or acrofacial dysostosis is a rare and complex malformation characterized by ear anomalies, micrognathia, radial limb hypoplasia, and absence of the thumb or other fingers. Since the original description of the syndrome in 1948, there have only been four reports of prenatal diagnoses in the literature, all during the second trimester, and only two of them had anatomopathological correlations. We describe a case of Nager syndrome that was suspected in the third trimester of gestation and confirmed postnatally through pathology. The mother was white, 27 years old, and G5P2A2, with a family history of a brother with a harelip. She was referred to our service at 33 weeks of pregnancy with an ultrasound fetal diagnosis of musculoskeletal dysplasia associated with severe micrognathia and severe polyhydramnios. Birth was by means of cesarean section because of suspected fetal distress, which resulted in extraction of a live male fetus with Apgar 1/4, weight of 1,505 g, severe mandibular hypoplasia, low-set ears, severe upper-limb shortening, and absent left thumb. Death occurred 4 h after birth. Anatomopathological examination confirmed the diagnosis of Nager syndrome.

Second‐trimester prenatal diagnosis of Nager syndrome with a deletion including SF3B4 detected by chromosomal microarray

“…Acrofacial dysostoses (AFDs) are a clinically heterogeneous group of disorders. Two major groups have been distinguished using postnatal clinical features, dependant on the type of limb defect: predominant preaxial defects (including Nager syndrome) and postaxial malformations (including Genee‐Wiedemann or Miller syndromes) . Preaxial abnormalities are caused by abnormal development of the first and second branchial arches and limb buds …”

“…Two major groups have been distinguished using postnatal clinical features, dependant on the type of limb defect: predominant preaxial defects (including Nager syndrome) and postaxial malformations (including Genee-Wiedemann or Miller syndromes). 1,2 Preaxial abnormalities are caused by abnormal development of the first and second branchial arches and limb buds. 3 Nager syndrome (NS), first described by Nager and de Reyenie in 1948 (MIM #154400), is the most common form of AFD (also called mandibulofacial dysostosis or acrofacial dysostosis type 1; AFD1).…”