The Nager syndrome

Abstract

The Nager syndrome was identified in a newborn infant and in a subsequent sib by prenatal ultrasonography. This report documents an autosomal recessive pattern of inheritance for this disorder.

Nager acrofacial dysostosis: Male‐to‐male transmission in 2 families

“…Prenatal diagnosis for severe forms of radial dysplasia is feasible and prenatal ultrasound observations of this condition have been reported [Hecht et al, 1987;Benson et al, 19881. Hirschsprung disease is a developmental anomaly involving the neural crest [Webster, 19731 and it has occasionally been observed in malformation syndromes that include anomalies of the limbs and/or craniofacial region [Bodian and Carter, 1963;Laurence et al, 1975;Goldberg and Shprintzen, 1981;Reynolds et al, 1983;Saul, 1985;Santos et al, 1988;Clayton-Smith and Donnai, 19891. To our knowledge, the association of acrofacia1 dysostosis with Hirschsprung disease, present in our second family, has not been reported previously.…”

“…More severely affected cases have been described under the same eponym [Pfeiffer and Stoess, 1983;Kawira et al, 1984;Krauss et al, 1985;Hecht et al, 1987;Goldstein and Mirkin, 1988;Hall, 1989;Le Merrer et al, 1989;Palomeque et al, 19901 and the possible causal heterogeneity implied by this phenotypic variability has been pointed out by several authors [Carey et al, 1978;Weinbaum et al, 1981;Halal et al, 1983;Goldstein and Mirkin, 1988;Hall, 19891. Support for classifying all of these cases as Nager acrofacial dysostosis comes from observations that rather great intra-familial variability may occur [Le Merrer et al, 1989;Hall, 1989;Kim et al, 19891. Causal heterogeneity is suggested by families that are consistent with both dominant and recessive patterns of inheritance.…”

“…The observation of affected monozygotic twins [Byrd et al, 19881 is consistent with causation by a single mutant gene and either dominant or recessive expression. Reports of affected sibs with unaffected parents [Walker, 1974;Hecht et al, 1987;Chemke et al, 19881 and one sporadic case whose parents were first cousins [Burton and Nadler, 19771 suggest that some cases may be of autosomal recessive etiology. On the other hand, parent-to-child transmission has been observed.…”

“…In addition, reported patients have had a variety of other findings including developmental delay, short stature, and other components of mandibulofacial dysostosis such as cleft palate, ear anomalies, hearing loss, absent or sparse eyelashes, and downslanting palpebral fissures [Bowen and Harley, 1974;Lowry, 1977;Gellis et al, 1978;Halal et al, 1983;Thompson et al, 1985;Meyerson and Nisbet, 1987;Byrd et al, 1988;Chemke et al, 19881. This phenotype usually occurs sporadically but causal heterogeneity is suggested by families that are consistent with both recessive [Walker, 1974;Hecht et al, 1987;Chemke et al, 19881 and dominant [Weinbaum et al, 1981;Hall, 1989;Kim et al, 1989;Le Merrer et al, 19891 patterns of inheritance. No previous cases of male-to-male transmission have been reported.…”

Otologic and audiologic features of Nager acrofacial dysostosis

“…The mandibulofacial features of Nager syndrome include down-slanting palpebral fissures, malar hypoplasia, atretic external auditory canals, severe micrognathia, high nasal bridge, and absent velum [8]. The preaxial limb malformations include hypoplastic or missing thumbs, hypoplastic radii, and shortened humerus bones.…”