Child with manifestations of Nager acrofacial dysostosis, and the MURCS, VACTERL, and pulmonary agenesis associations: Complex defect of blastogenesis?

Abstract

Nager acrofacial dysostosis (NAFD) combines the facial anomalies of mandibulofacial dysostosis (Treacher‐Collins‐Francescetti) with hypoplastic/aplastic or triphangeal thumbs. The MURCS association consists of Müllerian duct aplasia, renal aplasia, cervicothoracic somite dysostosis with Klippel‐Feil anomaly, and often defects of the facio‐auriculo‐vertebral (Goldenhar) spectrum. We describe a child with NAFD, MURCS anomaly (Klippel‐Feil anomaly, vertebral synostoses, left renal agenesis), and left pulmonary agenesis. Our proband appears to express a unique anomaly of blastogenesis, simultaneously affecting the acrorenal, the mandibulofacial, and the cervicothoracic developmental fields, combining clinical manifestations of the MURCS, NAFD, VACTERL, and pulmonary agenesis associations. All anomalies may be traced back to abnormal blastogenesis, occurring during the third or the fourth week of embryonic development, and show that NAFD is a polytopic developmental field defect. © 1996 Wiley‐Liss, Inc.

Acrofacial dysostosis (AFD) with preaxial limb hypoplasia (Nager AFD) and club foot diagnosed in a fetus from 1812 in the anatomical collections at the University of Halle, Germany

“…Furthermore, NAFD in combination with club foot has only been reported five times [Opitz et al, 1993;Kubota et al, 2001]. The more severe the syndrome, as in stillborn babies, the more frequently are lower limb anomalies found [David et al, 1996;Kubota et al, 2001;Paladini et al, 2003]. In addition to NAFD, the fetus we studied shows a change in the position of the foot or club foot on the right side, unilateral tibial torsion on the left side, and a single umbilical artery.…”

“…Thus, the facial malformations show that NAFD is primarily or predominantly a defect of blastogenesis, presumably an abnormality of cranial neural crest development [Opitz et al, 1993;David et al, 1996]. Deformations of the external ear and dislocation of the ear capsule/petrosum occur facultatively [Opitz et al, 1993;David et al, 1996]. Radiographic and CT evaluation of the fetus we studied, documented unilateral hypoplasia of the mandible, bilateral middle ear deformities, and dislocation of the ear capsule.…”

“…The severity of the NAFD varies extremely between affected individuals, ranging from severe malformations and intruterine death to very mild forms, which may easily escape correct diagnosis [Opitz et al, 1993;David et al, 1996;Fryns et al, 1996;Hunt and Hobar, 2002]. The main facial characteristics for the pathological-anatomical diagnosis are mandibular hypoplasia, velar hypoplasia, and zygomatic bone hypoplasia [Opitz et al, 1993[Opitz et al, , 1998Hunt and Hobar, 2002].…”

“…In addition, patients with NAFD often have further abnormalities of the branchial arches, including involvement of the auditory canal, the middle ear, and hypoplasia of the larynx [Opitz et al, 1993[Opitz et al, , 1998]. Thus, the facial malformations show that NAFD is primarily or predominantly a defect of blastogenesis, presumably an abnormality of cranial neural crest development [Opitz et al, 1993;David et al, 1996]. Deformations of the external ear and dislocation of the ear capsule/petrosum occur facultatively [Opitz et al, 1993;David et al, 1996].…”

“…A single umbilical artery has been observed at least twice [Opitz et al, 1993[Opitz et al, , 1998]. The literature suggests that NAFD is in most cases a ''pure'' polytopic mandibulofacial dysostosis/acral field defect [Opitz et al, 1993;David et al, 1996]. Opitz et al [1993] postulated the occurrence of a presumptive group of cells in the primary field which exerts an inductive effect during gastrulation on Fig.…”