Nager Acrofacial Dysostosis: A Case Series with Literature Review and Update

Nager Acrofacial Dysostosis: a case series with literature review and update

Statement of the problem

Nager acrofacial dysostosis (AFD) was first described by Nager and de Reynier in 1948. It is a genetic disorder with a varied opinion on etiology. 

The major facial features of Nager syndrome include down-slanted palpebral fissures, midface retrusion and micrognathia, the latter of which often requires the placement of a tracheostomy in early childhood and feeding through a gastrostomy tube.  Limb defects typically involve the anterior (i.e. radial) elements of the upper limbs and manifest as small or absent thumbs, tri-phalangeal thumbs, radial hypoplasia or aplasia and radio-ulnar synostosis.  Phocomelia of the upper limbs and, occasionally, lower-limb defects have also been reported.

The presence of anterior upper-limb defects as opposed to posterior upper-limb defects and the typical lack of lower-limb involvement distinguishes Nager syndrome from Miller syndrome, another rare AFD.

These patients require multiple surgeries at different stages of their lives including cleft palate repair, mandibular lengthening with distraction osteogenesis, orthognathic surgery, among others, including bone grafts and ramus reconstruction.²

Materials and methods 

An extensive literature search of the published data was completed using MEDLINE, Google Scholar, and PubMed databases. The search included the terms ‘Nager syndrome’ and ‘acrofacialdysostosis.’ It was limited to the English language. 

Results

The literature search found 54 articles reporting on patients with Nager syndrome. After careful review 6 were excluded either due to the irrelevance of subject matter or the case having already been reported earlier with no additional clinical benefit in the new report. The articles reviewed provided new information concerning genetic etiology of the syndrome and new treatment modalities for complications.

We report the 95^th, 96^th and 97^th case of Nager syndrome detailing their treatment.  An update on the literature is presented with particular attention to etiology and new surgical procedures to treat features of the syndrome.

Conclusions

Nager syndrome is rare, with fewer than 100 cases reported at present. Both autosomal dominant and autosomal recessive segregation has been reported; leading many to postulate that Nager syndrome is genetically heterogeneous. These patients require multiple surgeries to correct defects and relapse is a known complication.^{1, 2}

Our cases show, with surgery, correction of the facial deformity can be achieved. This may allow for tracheostomy decannulation and removal of the gastrostomy tube in many patients. The institution of normal respiration and feeding with improvement in hearing and physical appearance can greatly increase the quality of life of patients with Nager syndrome. 

References:

1. Francois P. Bernier, Oana Caluseriu, Sarah Ng, Jeremy Schwartzentruber, Kati J. Buckingham, A. MicheilInnes, Ethylin Wang Jabs, Jeffrey W. Innis, Jane L. Schuette, Jerome L. Gorski, PeterH.Byers, et al.  Haploinsufficiency of SF3B4, a Component of the Pre-mRNA Spliceosomal Complex, Causes Nager Syndrome. Am.J.Hum.Genet. 90, 925–933, 2012
2. Thomas Schlieve, Maha Almusa, Michael Miloro, and Antonia Kolokythas. Temporomandibular Joint Replacement for Ankylosis Correction in Nager Syndrome: Case Report and Review of the Literature. J Oral Maxillofac Surg. 70, 616-625, 2012