Table of Contents  
CASE REPORT
Year : 2013  |  Volume : 5  |  Issue : 2  |  Page : 138-142

Nager's acrofacial dysostosis


1 Department of Oral Medicine and Radiology, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India
2 Department of Oral Medicine and Radiology, Sri Dharmasthala Manjunatheshwara College of Dental Sciences and Hospital, Dharwad, Karnataka, India

Date of Web Publication3-Jan-2014

Correspondence Address:
Arpita Rai
Department of Oral Medicine and Radiology, Faculty of Dentistry, Jamia Millia Islamia, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-8844.124263

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  Abstract 

Acrofacial dysostosis (AFD) is a generic name for a variety of different but possibly related genetic disorders that result in craniofacial and limb malformations and are, therefore, categorized under oroacral disorders. Several different variants have been identified and Nager preaxial AFD represents the association of mandibulofacial dysostosis with limb anomalies, particularly hypoplasia of the radial aspect of the hand. This report features a case of a 21-year-old male presenting with malar hypoplasia, downward sloping palpebral fissures, high-arched palate, radioulnar synostosis, hypoplasia of the right thumb and lower limb anomalies.

Keywords: Acrofacial dysostosis, Nager′ syndrome, Preaxial acrofacial dysostosis


How to cite this article:
Rai A, Nandimath KR, Sattur AP, Naikmasur VG. Nager's acrofacial dysostosis. J Orofac Sci 2013;5:138-42

How to cite this URL:
Rai A, Nandimath KR, Sattur AP, Naikmasur VG. Nager's acrofacial dysostosis. J Orofac Sci [serial online] 2013 [cited 2019 Dec 6];5:138-42. Available from: http://www.jofs.in/text.asp?2013/5/2/138/124263


  Introduction Top


Nager preaxial acrofacial dystosis (AFD) is a rare congenital syndrome characterized by malformed mandibulofacial structures and preaxial upper limbs. [1] It was first recognized in a patient reported by Nager and de Reynier in 1948, [2] who used the term AFD to distinguish the condition from mandibulofacial dysostosis. The facial features include downward slanting palpebral fissures, absent eyelashes in the medial third of the lower lids, mandibular and malar hypoplasia, dysplastic ears with conductive deafness, and variable degrees of palatal clefting. Upper limb malformation is a constant feature of  Nager syndrome More Details and ranges from thumb hypoplasia to absence of the radial ray. [3] We present an interesting case of Nager syndrome presenting with not only craniofacial and upper limb defects but also exhibiting lower limb anomalies. This combination of findings of mandibulofacial dysostosis, radioulnar synostosis, asymmetrical hypoplasia of thumb and bilateral hallux abnormality has been rarely reported in previous literature.


  Case Report Top


A 21-year-old male patient reported to the department of oral medicine and radiology for routine dental complaints. Patient gave history of skeletal deformity of limbs since birth and also reported history of multiple decayed teeth since childhood. Patient was one of the three siblings of consanguineous parents with no family history of congenital abnormalities. Detailed history revealed that the pregnancy, labor, and delivery of the patient had been uneventful. However, he was hospitalized immediately after birth for failure to thrive. Rest of the neonatal course and infancy were unremarkable. Patient had undergone surgical management of dacrocystitis at the age of 10 years.

Routine general physical examination revealed an association of mandibulofacial dysostosis with limb defects. Short stature with overall growth retardation was apparent, yet no evidence of mental retardation was seen. Craniofacial manifestations [Figure 1]a comprised downward slant of palpebral fissures, ptosis of upper eyelids, and deficient eyelashes especially in the medial one third of lower eyelids. Scar from previous surgery below the medial canthus of right eye was visible. Hypoplasia of the malar eminences was unmistakable but micrognathia was not so apparent clinically. An increase in gonial angle was evidenced on profile view [Figure 1]b. Ears were dysplastic, low-set, and outstanding; however, no hearing disturbances were recorded. There was no restriction of jaw movements. Intraorally, clinical examination revealed crowding of teeth and multiple decayed teeth in both the arches [Figure 2]a. A high arched palate was present [Figure 2]b. Upper limb anomalies were characterized by hypoplasia of right thumb which appeared rudimentary and was attached to palm only by soft tissue. There was thenar and hypothenar atrophy bilaterally. Though extension movements at the elbow joints were normal, clinically elbow deformity was evident which was more pronounced on right than left. Lower limbs showed short and broad halluces bilaterally along with increased web space between 1 st and 2 nd toes. The remainder of the systemic evaluation, following referrals to otolaryngology, ophthalmology, urology, and internal medicine departments, was insignificant.
Figure 1: Extraoral photographs of the patient showing zygomatic b hypoplasia, downslanting palpebral fissures, mandibular hypoplasia, low-set ears (a) Frontal view, (b) Profile view

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Figure 2: Intraorally photographs (a) Crowding of teeth and multiple decayed teeth in both the arches seen, (b) Shows high arched palate

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The maxillofacial skeleton was examined radiographically. The orthopantomogram [Figure 3] observation revealed increased gonial angle, especially in the left side, deep sigmoid notch, well-developed coronoid process, and relatively underdeveloped condylar process. Crowding of teeth and carious involvement of multiple teeth was evidenced. Lateral cephalogram tracing [Figure 4] revealed severe skeletal class II malocclusion with normodivergent growth pattern, tending toward hyperdivergence. The facial angle was 75 ° (normal range: 82-95 ° ) indicating posterior positioning of the mandible in relation to the midface. The distance between the lower lip and the esthetic plane of Ricketts (E plane) was 1 mm (normal range: 1.8-2.2 mm). The anterior cranial base length was 65 mm, mandibular corpus measured 61 mm, and ramus height was 48 mm. Further, analysis revealed that though ramal length was normal in relation to cranial base, corpus length fell short by 7.3 mm [Ideal corpus length = 1.05 × anterior cranial base length (65 mm), therefore 68.3 mm for this patient]. Radiological examination confirmed proximal radioulnar synostosis and subluxation of elbows [Figure 5]. Further, radiologic examination of hand and wrist revealed absence of 1 st metacarpal bone, except a rudimentary head on right side and evidence of hypoplasia of thumb and 1 st metacarpal of left hand. In general, all the metacarpal bones were slender and all carpal bones had not appeared. Asymmetric thumb anomalies in association with radioulnar synostosis in a patient manifesting craniofacial anomalies indicated preaxial acrofacial dysostosis. A-P feet radiograph demonstrated widening and thickening if 1 st web space, along with short distorted phalanges of great toe bilaterally.
Figure 3: Orthopantomogram of the patient showing increased gonial angle, especially in the left side, deep sigmoid notch, well-developed coronoid process, and relatively underdeveloped condylar process

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Figure 4: Lateral cephalometric tracing. Ricketts' analysis and various linear measurements are illustrated Facial angle– 75°, Facial axis– 84.1°, Lower facial height– 61°, Mandibular arc– 18°, Lower incisor to A-Pogonion line– 4 mm, Upper molar to Pterygo-vertical planes PTV-4 mm, Lower lip to E plane-1 mm

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Figure 5: Radiograph of hand and wrist showing proximal radioulnar synostosis and subluxation of elbows

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The diagnosis of Nager AFD was made based on clinical and imaging features. Endodontic consultation and opinion regarding surgical correction of limb anomalies was sought. Patient is currently undergoing treatment for functional and esthetic corrections.


  Discussion Top


Nager AFD belongs to a rather heterogeneous group of genetic disorders comprising defects of cranial neural crest and limb development. [4] AFD can be widely divided into two broad categories-Preaxial and postaxial AFD, depending on medial or lateral involvement of limbs, respectively. The predominantly preaxial form of AFD is Nager syndrome; however, Catania form of AFD; [5] Palagonia form of AFD; [6] AFD syndrome of Kelly, Cooke, and Kester; [7] AFD syndrome of Reynolds; [8] Rodrigues or Madrid form of AFD; [9] AFD syndrome of Richieri-Costa; [10] and the Patterson-Stevenson-Fontaine syndrome [11] have also been described as preaxial AFD. The predominant postaxial AFD is known as Geene-Wiedemann or Miller syndrome. [12]

The Nager syndrome is a rare disorder resulting from developmental abnormalities of the first and second branchial arches and manifests from lesions occurring between weeks 3 and 4 of blastogenesis. [13] Sulik and Dehart [14] have suggested that the pathogenesis of Nager syndrome may be attributed to disturbances in development of the proximal aspects of the maxillary and mandibular prominences of the first branchial arch and the apical ectodermal ridges of the limb bud. Zori et al., [15] suggested that the gene mutation responsible for this disorder might reside on chromosome 9q. The mechanism of inheritance of Nager AFD has classically been described as sporadic, although many cases of autosomal recessive inheritance have been described. [16] Several reports also describe autosomal dominant patterns of inheritance associated with a spontaneous mutation. [17],[18]

Nager syndrome presents with characteristic clinical and radiologic findings. A brief description of these anomalies is provided in [Table 1]. The craniofacial complex in Nager AFD resembles Treacher-Collins syndrome and comprises of hypoplastic orbitomalar region results in downslanting palpebral fissures, ptosis of eyelids, olobomas and deficiency of eyelashes of lower eyelids, palatal defects and ear abnormalities. It is generally agreed that micrognathia is usually more marked than in Treacher-Collins syndrome and cases with upper airway obstruction, leading to respiratory and feeding difficulties have been previously reported. [13] The present case demonstrated most of the features of mandibulofacial dysostosis, but micrognathia was not as marked on clinical appearance as suggested in previously reported cases. [3],[19] Lateral cephalogram, however, revealed reduced corpus length by 7.3 mm and a posteriorly positioned mandible exhibiting severe class II skeletal relationship.
Table 1: Commonly encountered clinical and radiographic features in Nagar syndrome

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The upper limb anomalies in Nager AFD range from severe shortening of the radius to single abnormalities of the digits and present as hypoplasia or absence of radius, radioulnar synostosis, and hypoplasia or absence of the thumbs. Triphalangeal thumbs and index finger are equally characteristic. [20] Hypoplasia of right thumb presenting with radioulnar synostosis was diagnostic, if not pathognomominc, for categorizing this case as Nager AFD.

Lower limb anomalies are rarely observed in this syndrome. Those reported so far include hip dislocation in three previous cases, [19],[21],[22] complete aplasia of lower limbs with feet attached directly to the femora or trunk which was reported in a particularly severe form of Nager AFD, [23] equinovarus position of both feet, [24] and club foot reported on four previous occasions. [25],[26],[27],[28] The presence of short and broad halluces bilaterally with increased web space between 1 st and 2 nd toes and radiographic demonstration of widening and thickening if 1 st web space, along with short distorted phalanges of great toe bilaterally seen in the present case has been rarely reported.

Differential diagnosis of Nager syndrome includes Treacher-Collins syndrome, AFD-type Rodriguez, Richieri-Costa-Pereira syndrome and Trisomy18. Comparison of major clinical features of these syndromes is given in [Table 2]. Prenatal diagnosis of Nager AFD can be carried out by ultrasonography, as early as 20 th week of gestation. [4] Early prenatal recognition of the syndrome is important both to provide parents with the option of pregnancy termination and, in case of pregnancy continuation, to arrange delivery in a tertiary referral center as neonates with Nager syndrome may present with acute upper airway obstruction and feeding difficulties due to severe micrognathia. The postnatal diagnosis can be established relying on clinical and radiological features. The overall prognosis of Nager AFD is good and after infancy most patients are healthy and presumed to have normal life span. Normal development of Nager AFD patients depends on a multidisciplinary team approach that understands the genetics and natural history of this interesting syndrome.
Table 2: Differential diagnosis of Nagar syndrome

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  References Top

1.Hall B. Nager acrofacial dysostosis: Autosomal dominant inheritance in mild to moderately affected mother and lethally affected phocomelic son. Am J Med Genet 1989;33:394-7.  Back to cited text no. 1
    
2.Nager FR, de Reynier JP. Das gehororgan bei den angeborenen kopfmissbildungen. Pract Otorhinolaryngol (Basel) 1948;10(Suppl 2):1-128.  Back to cited text no. 2
    
3.Giugliani R, Pereira CH. Nager's acrofacial dysostosis with thumb duplication: Report of a case. Clin Genet 1984;26:228-30.  Back to cited text no. 3
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4.Vargervik K. Mandibular malformations: Growth characteristics and management in hemifacial microsomia and Nager syndrome. Acta Odontol Scand 1998;56:331-8.  Back to cited text no. 4
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5.Opitz JM, Mollica F, Sorge G, Milana G, Cimino G, Caltabiano M. Acrofacial dysostoses: Review and report of a previously undescribed condition: The autosomal or X-linked dominant Catania form of acrofacial dysostosis. Am J Med Genet 1993;47:660-78.   Back to cited text no. 5
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7.Kelly TE, Cooke RJ, Kester RW. Acrofacial dysostosis with growth and mental retardation in three males, one with simultaneous Hermansky-Pudlak syndrome. Birth Defects Orig Artic Ser 1977;13:45-52.  Back to cited text no. 7
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13.Ho AS, Aleshi P, Cohen SE, Koltai PJ, Cheng AG. Airway management in Nager Syndrome. Int J Pediatr Otorhinolaryngol 2008;72:1885-8.  Back to cited text no. 13
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14.Sulik KK, Dehart DB. Retinoic-acideinduced limb malformations resulting from apical ectodermal ridge cell death. Teratology 1988;37:527-37.  Back to cited text no. 14
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15.Zori RT, Gray BA, Bent-Williams A, Driscoll DJ, Williams CA, Zackowski JL. Preaxial acrofacial dysostosis (Nager syndrome) associated with an inherited and apparently balanced X 9 translocation: Prenatal and postnatal late replication studies. Am J Med Genet 1993;46:379-83.  Back to cited text no. 15
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16.Chemke J, Mogilner BM, Ben-Litzhak I, Zurkowsi L, Ophir D. Autosomal recessive inheritance of Nager acrofacial dysostosis. J Med Genet 1988;25:230-2.  Back to cited text no. 16
    
17.Lowry B. The Nager syndrome (acrofacial dysostosis): Evidence for autosomal dominant inheritance. Birth Defects Orig Artic Ser 1977;13:195-202.  Back to cited text no. 17
    
18.Aylsworth AS, Lin AE. Male to male transmission in a second family supports autosommal dominant inheritance in Nager acrofacial dysostosis. Am J Hum Genet 1990;47:47A.  Back to cited text no. 18
    
19.Krauss CM, Hassell LA, Gang DL. Anomalies in an infant with Nager acrofacial dysostosis. Am J Med Genet 1985;21:761-4.  Back to cited text no. 19
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21.Klein D, König H, Toller R. Sur une forme extensive de dysostose mandibulofaciale (Franceschetti) accompagnee de malformations des extremities. Rev Otoneuroophtalmol 1970;42:432-40.  Back to cited text no. 21
    
22.Meyerson MD, Jensen KM, Meyers JM, Hall BD. Nager acrofacial dysostosis: Early intervention and long-term planning. Cleft Palate J 1977;14:35-40.  Back to cited text no. 22
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23.Goldstein DJ, Mirkin LD. Nager acrofacial dysostosis: Evidence of apparent heterogeneity. Am J Med Genet 1988;30:741-6.  Back to cited text no. 23
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24.Fryns JP, Bonhomme A, van den Berghe H. Nager acrofacial dysostosis: An adult male with severe neurological deficit. Genet Couns 1996;7:147-51.  Back to cited text no. 24
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25.Gobbel L, Schultka R, Klunker R, Stock K, Wand D, Olsson L, et al. Acrofacial dysostosis (AFD) with preaxial limb hypoplasia (Nager AFD) and club foot diagnosed in a fetus from 1812 in the anatomical collections at the University of Halle, Germany. Am J Med Genet 2005;137A:263-8.   Back to cited text no. 25
    
26.Palomeque A, Pastor X, Ballesta F. Nager anomaly with severe facial involvement, microcephaly, and mental retardation. Am J Med Genet 1990;36:356-7.  Back to cited text no. 26
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28.Kubota H, Noguchi Y, Urabe K, Itokawa T, Nakashima Y, Iwamoto Y. Flexor digitorum longus accessorius in the club foot of an infant with Nager syndrome. Arch Orthop Trauma Surg 2001;121:95-6.  Back to cited text no. 28
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

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