5 Acrofacial Dysostosis, Nager Type
Mandibulofacial dysostosis with limb anomalies, preaxial acrofacial dysostosis, AFD1
Downward slanting palpebral fissures, malar hypo- plasia, micrognathia, hypoplastic/absent thumb, up- per limb anomalies
Frequency: Fewer than 100 published cases.
Genetics
Autosomal dominant (OMIM 154400), with marked- ly variable penetrance and expressivity; gene locus maps at 9q32; paternal age effect; probably heteroge- neous with an autosomal recessive form.
Clinical Features
• Antimongoloid slant of palpebral fissures, ptosis of lower lids, hypoplastic lower lid eyelashes, pro- jection of scalp hair onto lateral cheeks
• Malar hypoplasia
• Micrognathia, cleft palate
• Low-set ears, microtia, cup-shaped ears, external ear canal defects, conductive hearing loss
• Rudimentary nipples
• Radial defects
• Thumb defects
• Usually normal lower limbs
• Cryptorchidism
• Short stature Differential Diagnosis
• Treacher-Collins syndrome
• Acrofacial syndrome, Miller or postaxial type
Radiographic Features Skull
• Malar hypoplasia
• Severe micrognathia Limbs
• Radial ray abnormalities, including radial hypo- plasia/aplasia (nearly all patients) and thumb hy- poplasia/aplasia (75%)
• Radioulnar synostosis (25%)
• Thumb anomalies other than hypoplasia/aplasia (triphalangeal thumb, symphalangism, duplica- tion, syndactyly between thumb and index finger)
• Carpal fusions
• When present, mild abnormalities of lower limbs (clubfoot, hypoplasia/aplasia of great toe, duplica- tion of hallux, metatarsus varus)
Pelvis
• Hip dysplasia Chest
• Rib anomalies
• Pectus excavatum Spine
• Scoliosis
• Cervical vertebrae anomalies
Acrofacial Dysostosis, Nager Type 588
Fig. 5.1. Patient 1, newborn. Antimongoloid slanting of palpe- bral fissures, severe micrognathia, low-set and dysmorphic ears
589
A
Acrofacial Dysostosis, Nager Type
Fig. 5.2. Patient 2, newborn. There are malar hypoplasia and severe micrognathia. The skull is disproportionately large rel- ative to the facial bones
Fig. 5.3. Patient 2, newborn. Anomalies in the number of the ribs can be seen (11 on left, 10 ribs on right side). Note also anomalies of the cervical spine
Fig. 5.4. Patient 2, newborn. Both acetabula are poorly formed, with bilateral hip dysplasia. Retarda- tion in the ossification of the pu- bic bones is also evident
Acrofacial Dysostosis, Nager Type 590
Bibliography
Goldstein DJ, Mirkin LD. Nager acrofacial dysostosis: evidence for apparent heterogeneity.Am J Med Genet 1988; 30: 741–6 Halal F, Herrmann J, Pallister PD, Opitz JM, Desgranges MF, Grenier G. Differential diagnosis of Nager acrofacial dysos- tosis syndrome: report of four patients with Nager syn- drome and discussion of other related syndromes. Am J Med Genet 1983; 14: 209–24
Hecht JT, Immken LL, Harris LF, Malini S, Scott CI. The Nager syndrome. Am J Med Genet 1987; 27: 965–9
Lowry RB. The Nager syndrome (acrofacial dysostosis): evi- dence for autosomal dominant inheritance. Birth Defects Orig Artic Ser 1977; 13: 195–220
Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarot- ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990
McDonald MT, Gorski JL. Nager acrofacial dysostosis. J Med Genet 1993; 30: 779–82
Opitz JM. Nager “syndrome” versus “anomaly” and its noso- logy with the postaxial acrofacial dysostosis syndrome of Genee and Wiedemann. Am J Med Genet 1987; 27: 959–64 Zori RT, Gray BA, Bent-Williams A, Driscoll DJ, Williams CA,
Zackowski JL. Preaxial acrofacial dysostosis (Nager syn- drome) associated with an inherited and apparently bal- anced X;9 translocation: prenatal and postnatal late repli- cation studies. Am J Med Genet 1993; 46: 379–83
Fig. 5.5 a, b. Patient 2, newborn.
Bilateral thumb aplasia. Short middle phalanges of the 2nd and 5th fingers. Short forearms, with proximal radioulnar synostosis on both sides. (Reprinted, with per- mission, from Mastroiacovo et al.
1990)
Fig. 5.6. Patient 2, newborn. The great toe is markedly short and wide, with severe hypoplasia of the distal phalanx. The phalanges of the remaining toes are either hypoplastic or ab- sent
a b
