Rare condition characterized by malar hypoplasia,
maxillary and mandibular hypoplasia, cleft lip or palate, retroplaced
tongue, radial defects (preaxial limb deficiency), downward-slanting
palpebral fissures, absent eyelashes (medial third of lower lids),
dysplastic ears and conduction deafness, trismus, and respiratory problem in
neonates. There may be underdevelopment or absence of the thumb, shortened
forearms, and poor movement in the elbow.
Acrofacial Dysostosis 1; Treacher Collins Mandibulofacial
Dysostosis Type with Limb Anomalies; Split-Hand Deformity Mandibulofacial
Nager and de Reynier recognized this condition as a
specific entity in 1948. Opitz (1987) suggested that Nager acrofacial
dysostosis (AFD) represents an “anomaly” rather than a syndrome because of
its apparent causal heterogeneity.
Rare malformation, of which several syndromic
associations have been reported.
No clear genetic background and no molecular
data. Most cases have been sporadic. However, it has also been suggested
that a dominant mutation was possible. In 1987, the presentation of a father
and child consistent with Nager syndrome supported an autosomal dominant
inheritance, but no further investigations were able to sustain this
observation. It has been reported that a deletion of the heterochromatic
block and adjacent euchromatin of chromosome 1q was possible. In this
situation, the affected child also presented with severe aortic stenosis and
right pulmonary bronchial stenosis. This association with a deletion of
chromosome 1q may suggest that this gene region contains crucial information
for normal limb, craniofacial, and/or cardiopulmonary development. The
association with chromosome 9 has been reported. An infant with Nager
syndrome and a chromatid gap within band 3p14 was reported, but there
remains no indication that this disease is genetic rather than sporadic.
Opitz (1987) suggested that Nager AFD represents an “anomaly” rather than
a syndrome because of its apparent causal heterogeneity.
No known pathophysiologic explanation for this
The diagnosis seems mostly clinical and radiologic. The
limb deformities consist of absence of radius, radioulnar synostosis, and
hypoplasia or absence of the thumbs. The mandibulofacial dysostosis is
characterized mainly by severe micrognathia and malar hypoplasia. They
suggested that ptosis of the lower lids, hypoplasia of the lower lid
eyelashes, and cartilaginous pegs between the antitragus and lobule are
minimal expressions of the syndrome. At birth, the diagnosis is suspected
based on the clinical aspect, characterized by varying severities of
mandibulofacial dysostosis with preaxial and/or postaxial limb
In the predominant facial form, called Nager acrofacial dysostosis, the
facial changes resemble strikingly those of the Treacher Collins syndrome:
malar hypoplasia, maxillomandibular hypoplasia, cleft lip or palate,
conductive hearing loss, and radial limb hypoplasia. Neonates may present
respiratory or feeding problems because of severe mandibular hypoplasia.
Upper limb malformation is a constant feature of Nager syndrome and ranges
from thumb hypoplasia to the absence of the radial ray. Intelligence is
usually normal. Neurologic: Hydrocephalus, agenesis of corpus callosum, polymicrogyria,
and spinal cord defects are reported. Airway: Absence of zygomatic arches associated
with hypoplastic malar ...