Download Preaxial acrofacial dysostosis (Nager syndrome): a case report

Journal of Disability and Oral Health (2007) 8/2 91–94
Preaxial acrofacial dysostosis (Nager
syndrome): a case report
A Da Silveira DDS MS PHD1, A S Joshi MDS M(ORTH)RCS2
and M Shahani MD3
1
Chief of Orthodontics and Assistant Professor, 2Orthodontic Research Fellow, 3Director of Pediatric Services and
Assistant Professor, The Craniofacial Center and Department of Pediatrics, University of Illinois, Chicago, Illinois,
USA.
Abstract
This case report describes the surgical and dental management of a 12-year-old girl with preaxial acrofacial
dysostosis also known as Nager syndrome. It highlights the importance of multidisciplinary treatment at
an early age and the effect of parental noncompliance on the overall physical and psychological development
of a medically compromised patient.
Key words: Nager syndrome, mandibulofacial dysostosis, multidisciplinary care
Introduction
Preaxial acrofacial dysostosis is a rare condition combining
the features of mandibulofacial dysostosis and limb abnormalities. It was first recognised as a specific entity by Nager
and de Reynier (1948), but was probably first reported by
Slingenberg (1908).
The craniofacial deformities seen in Nager acrofacial
dysostosis include downward slanting palpebral fissures,
malar hypoplasia, high nasal bridge, micrognathia and
external ear defects. Lateral extension of scalp hair onto the
cheeks, reduced number of eyelashes and lower lid
colobomas occur less frequently; while conductive hearing
loss is seen frequently. Predominant oral findings include
cleft palate and an absent soft palate. Typical upper limb
abnormalities include absent radii, radioulnar synostosis and
hypoplastic or absent thumbs. Lower limb anomalies also
seen are absent tibia/fibula, talipes equinovarus and dislocated hips (McDonald and Gorski, 1993). Other structural
malformations seen less frequently are tetralogy of Fallot,
spina bifida, scoliosis, renal agenesis or malposition, duplicated calyces, bicornuate uterus. A few patients also exhibit
microcephaly, hydrocephalus and mental retardation
(Guigliani and Pereira, 1984).
The inheritance pattern of Nager syndrome is largely
unknown. Most of the cases are sporadic. In offspring of
mildly affected parents, the inheritance may be autosomal
dominant, but some autosomal recessive cases have also
been reported (Kavadia et al., 2004). Some case reports have
documented drug exposure during the first trimester;
however, there is no conclusive proof of teratogenic
potential (Halal et al., 1983).
Nager syndrome is often misdiagnosed or not diagnosed
at all. A differential diagnosis to distinguish it from TreacherCollins, Miller and Pierre Robin syndromes is essential (Halal
et al., 1983). Patients with Treacher-Collins syndrome have
more severe forms of hypoplastic zygomata, downward
slanting palpebral fissures, lower lid colobomata and hypoplastic maxillae. In Nager syndrome patients, a higher
degree of mandibular hypoplasia and greater frequency of
palatal and limb abnormalities are seen as compared to
Treacher-Collins syndrome, where severity is concentrated
in the midface area (Danziger et al., 1990). Pierre Robin
sequence presents with the characteristic features of retrognathia, glossoptosis, cleft palate and airway obstruction
(Hunt and Hobar, 2002). Several variants of acrofacial
dysostoses with varying levels of severity have been
described such as Genée-Wiedemann syndrome and
Rodríguez-type acrofacial dysostosis (Dimitrov et al., 2005).
Miller acrofacial syndrome shows postaxial limb changes
associated with facial deformities, while in Nager syndrome,
the limb deformities are preaxial (OMIM, 2006).
Case report
A 12-year-old Caucasian girl was referred by the school
nurse to the Craniofacial Center for treatment of severe
dental and speech problems. She was initially diagnosed with
Pierre Robin syndrome and received treatment for repair
of the cleft palate in another institution. The patient was
undergoing speech therapy at school with no marked improvement.
The patient’s mother denied any significant medical problems and attributed her speech and intellectual defects to
her congenital illness. However, records taken by the school
nurse revealed that she had an asthma attack at 15 months
92 Journal of Disability and Oral Health (2007) 8/2
Figure 1. Frontal facial picture showing malar hypoplasia
with slight downward slant of the orbits, reduced number of
eyelashes on the lower eyelid and cupping of the left ear.
of age and was treated in the emergency room. School
records also showed in her past history that the patient was
delayed in all the milestones of development. She also
suffered from asthmatic attacks triggered by cold weather,
which were managed by metered dose inhalers and nebuliser
treatment. She had previously been diagnosed as having a
‘third degree’ curvature of the spine, which the parents were
advised to leave untreated. However, the scoliosis could
not be substantiated. She had also been evaluated for hearing loss several times in school as a possible reason for her
poor academic performance and was diagnosed as having
bilateral fluctuating conductive hearing loss. Tubes had been
placed four times in her ears, the last one placed at 9 years
of age.
At the time of her presentation to the Craniofacial
Center, the facial examination revealed malar hypoplasia,
slight downward slant of the orbits and left ear with a mild
cup deformity (Figure 1). The retrognathic convex profile
demonstrated a small mandible (Figure 2). Besides her
unusual facial appearance, the patient also had anomalies in
both hands with hypoplastic thumbs (Blauth I classification)
(Figure 3). Her right arm appeared thinner and weaker than
the left. This was confirmed by hand radiographs, which
showed hypoplastic phalanges of both thumbs, with
increased severity on the right thumb consistent with Nager
syndrome. Oral examination revealed severe dental caries
with plaque present, acute gingivitis and extremely poor oral
hygiene (Figure 4). She also presented a narrow V-shaped,
short palate with velopharyngeal insufficiency (Figure 5)
diagnosed by the team’s speech pathologist. Orthodontic
evaluation showed a retrognathic convex profile with a
vertical growth pattern and an anterior open bite with
increased overjet and an Angle’s Class II malocclusion. No
Figure 2. Profile photograph showing retrognathic convex
profile with a small mandible.
Figure 3. Both hands present with hypoplastic thumbs
(Blauth I classification).
lateral cephalogram radiograph was taken at the time of
her examination.
Speech evaluation revealed nasal speech due to the
velopharyngeal insufficiency. Audiological examination
showed that her hearing was normal and the conductive
hearing loss was due to accumulation of cerumen in the
narrow canals. Psychological evaluation placed her within
the Mentally Impaired Range with an intellectually deficient
level of functioning. The speech defect contributed to difficulties in verbal expression and resulted in behavioural
modification as an attempt to conceal her inadequacies.
Treatment was started for the patient with dental reha-
Da Silveira et al.: Nager syndrome: a case report
93
instructions in oral hygiene maintenance with regular brushing and flossing and periodic dental visits.
Despite good treatment results, the patient failed to keep
any further appointments and left the treatment incomplete.
Discussion
Figure 4. Severe dental caries with presence of plaque and
acute gingivitis, extremely poor oral hygiene and open bite
malocclusion with increased overjet.
Figure 5. Intra-oral photograph showing short palate and
velopharyngeal insufficiency.
bilitation being the first priority. This included restorations
as well as extractions, since several teeth were non-restorable.
Extraction of all permanent first molars and lower incisors
along with the deciduous right canine and right second
molar were performed under general anaesthesia. The
paediatric team then performed the restorative procedures,
which included composite restorations, caries control and
pulpectomies. Gingivectomy was performed in the lower
right quadrant.
After five months, a superiorly based pharyngeal flap
surgery was performed to improve the velopharyngeal
insufficiency. Subsequent follow-up appointments showed
that the patient’s speech was less hypernasal and more intelligible. Her oral hygiene also seemed to have improved. She
was scheduled for further restorative work and orthodontic treatment. The patient and her mother were also given
The combination of facial features with limb defects and
the presence of cleft palate indicated Nager syndrome in
this case. A common problem encountered in patients with
Nager syndrome is misdiagnosis and lack of awareness on
the part of the parents. There is some evidence of heredity
in this syndrome but most cases are sporadic. Many of the
earlier cases were reported as autosomal dominant; however some reports have found evidence of autosomal
recessive mode of inheritance (OMIM, 2006). A detailed
genetic counselling of family members of patients with
Nager syndrome is important to make them aware of
its heritability and increase their knowledge about this
condition.
Clinical management in such cases has relied on a
multidisciplinary approach for treatment. From birth and
during infancy, multiple surgical procedures may be required
to improve functional and aesthetic capabilities. In cases of
decreased jaw size, a tracheotomy may be necessary to
correct the airway obstruction and facilitate proper breathing (Friedman et al., 1996). Subsequently, feeding may rely
on a gastrostomy tube. When present, clefts should be
repaired in the early years. Hearing levels should be assessed
at this time and, if necessary, ventilation tubes and hearing
aids may be recommended if temporary or long-term hearing loss is present. In early childhood, speech and physical
therapies may be needed to improve speech and hand movements, respectively. The patient must be referred to an
orthopaedic surgeon for correction of limb defects.
Approaching the teenage period, the facial appearance,
including jaws and ears, can be improved by craniofacial
and jaw surgery coupled with orthodontics. Orthodontic
alignment of the teeth would be necessary for the presurgical
dental decompensations. Orthognathic surgical procedure
is indicated in most of these cases to correct the mandibular hypoplasia. Patients with minimal deformity require
either no treatment or a genioplasty to improve facial
appearance. Most of the patients have more severe forms
of micrognathia and require surgery for mandibular
advancement or mandibular distraction osteogenesis,
which is typically performed after post-pubertal growth is
completed (Stelnicki et al., 2002). A multidisciplinary approach
must be adopted early on in the treatment to address the
different problems faced by these patients. In this case, the
patient failed to continue treatment and orthodontic/
orthognathic care could not be attempted.
The provision of preventive and restorative dental care
is an important aspect in the multidisciplinary management
of these children. In medically compromised children, there
is a risk of developing systemic complications from dental
94 Journal of Disability and Oral Health (2007) 8/2
infections (Foster and Fitzgerald, 2005) and a consultation
with the primary health care provider is of absolute importance before undertaking any dental procedures. Antibiotic
prophylaxis prior to commencement of dental treatment is
essential to prevent any systemic complications from oral
infections, especially in patients with cardiac abnormalities.
Low income and minority children and those with
special health care needs are at a great risk for inadequate
access to oral health care. Factors contributing to this in the
United States include geographical maldistribution of clinicians and inadequate numbers of dentists treating children
with government-sponsored insurance (Mouradian et al.,
2004). To ensure adequate health care in such patients, an
increase in parent motivation and improved access to oral
health care in patients with special needs is essential.
References
Danziger I, Brodsky L, Perry, R, Nusbaum S, Bernat J, Robinson L.
Nager’s acrofacial dysostosis. Case report and review of the
literature. Int J Pediatr Otorhinolaryngol 1990; 20: 225–240.
Dimitrov B, Balikora I, Jekora N, Vakriloval, Fryns JP, Simeonor E.
Acrofacial Dysostosis Type Rodríguez. A J Med Genet 2005; 135
A: 81–85.
Foster H, Fitzgerald J. Dental disease in children with chronic illness.
Arch Dis Child 2005; 90: 703–708.
Friedman RA, Wood E, Pransky SM, Seid AB, Kearns DB. Nager
acrofacial dysostoses: Management of a difficult airway. Int. J. Pediatr
Otorhinolaryngol 1996; 35: 69–72.
Halal F, Hermann J, Pallister PD, Opitz JM, Desgranges MF, Greenier
G. Differential diagnosis of Nager acrofacial dysostosis syndrome:
Report of four patients with Nager syndrome and discussion of
other related syndromes. Am J Med Genet1983; 14: 209–224.
Hunt JA, Hobar PC. Common craniofacial anomalies: The facial
dysostoses Plast Reconst. Surg 2002; 110: 1714–1726.
Kavadia S, Kaklamanos E, Antoniadis K, Lafazanis K, Tramma, D. Nager
syndrome (preaxial acrofacial dysostosis): a case report. Oral Surg
Oral Med Oral Pathol Oral Radio Endo 2004; 97: 732–738.
McDonald MT, Gorski JL: Nager acrofacial dysostosis. J Med Genet
1993; 30: 779–782.
Giugliani R, Pereira CH. Nager’s acrofacial dysostosis with thumb
duplication: report of a case. Clin Genet 1984; 26: 228–230.
Mouradian WE, Crall, JJ. Disparities in children’s oral health and
access to dental care. J Am Med Assoc 2000; 284: 2625–2631.
Nager F, de Reynier J. Das Gehororgan bei den angeborenen Kopfmissbildungen Prac Otorhinolar (Basel) 1948; 10 (Suppl 2): 1–128.
Online Mendelian Inheritance in Man (OMIM). Acrofacial dysostosis
1, Nager type; AFD 1. 154400: 1-6. (http://www.ncbi.nlm.nih.gov/
Omim)
Slingenberg B. Missbildungen von Extremitäten. Virch Arch Pathol Anat
1908; 193: 1–91.
Stelnicki EJ, Lin WY, Lee C, Grayson BH, McCarthy JG. Long-term
outcome study of bilateral mandibular distraction: A comparison
of Treacher-Collins and Nager syndromes to other types of
micrognathia Plast Reconstr Surg 2002; 109: 1819–1825.
Address for correspondence:
Dr. Adriana Da Silveira
The Craniofacial Center
University of Illinois at Chicago
811 S Paulina Street, MC 841
Chicago, Illinois, USA.
60612- 7210.
Email: [email protected]