Prenatal sonographic diagnosis of Nager acrofacial dysostosis with unilateral upper limb involvement

Abstract

Nager acrofacial dysostosis is a rare form of acrofacial dysostosis first described by Nager and de Reynier, 1948. It is characterized by mandibulofacial dysostosis and limb anomalies. Typical craniofacial findings include down-slanting palpebral fissures, malar hypoplasia, micrognathia, abnormalities of the palate including high-arched hard palate, cleft palate or bifid uvula, small, low-set and posteriorly rotated ears, and abnormalities of the external and middle ear. Limb malformations associated with Nager acrofacial dysostosis most often involve the radial aspect of the upper limbs and may result in thumb hypoplasia or aplasia and/or aplasia/hypoplasia of the radius. Findings in a single affected individual are often not symmetrical but both upper limbs are usually involved. Severity can range from mild hypoplasia of the thumb to phocomelia. Radio-ulnar synostosis and abnormalities of the lower limbs have also been reported. Intelligence is typically normal. Congenital bilateral conductive hearing loss, speech difficulties and upper airway obstruction are common secondary to otologic and oral/mandibular abnormalities. A review of reported cases indicates wide variability in manifestations and severity of craniofacial and limb findings (Halal et al., 1983; Hall, 1989; Le Merrer et al., 1989; Danziger et al., 1990; Aylsworth et al., 1991). Cases of Nager acrofacial dysostosis are most often sporadic; however, several cases of autosomal dominant inheritance have been reported (Hall, 1989; Aylsworth et al., 1991). There are also reports of recurrence in children of unaffected parents, suggesting either autosomal recessive inheritance, possible germ line or somatic mosaicism, and, therefore, genetic heterogeneity (Chemke et al., 1988). Diagnosis depends on recognition of the phenotype, most often without a family history. A 23-year-old G2P0010 female presented for second trimester ultrasound at 20 weeks gestation based