5 Acrofacial Dysostosis, Nager Type

588 Acrofacial Dysostosis, Nager Type

Mandibulofacial dysostosis with limb anomalies, • When present, mild abnormalities of lower limbs preaxial acrofacial dysostosis, AFD1 (clubfoot, hypoplasia/aplasia of great toe, duplica- tion of hallux, metatarsus varus) Downward slanting palpebral ﬁssures, malar hypo- Pelvis plasia, micrognathia, hypoplastic/absent thumb, up- • Hip dysplasia per limb anomalies Chest • Rib anomalies Frequency: Fewer than 100 published cases. • Pectus excavatum Spine Genetics • Scoliosis Autosomal dominant (OMIM 154400), with marked- • Cervical vertebrae anomalies 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 hypoplasia/aplasia (nearly all patients) and thumb hypoplasia/aplasia (75%) • Radioulnar synostosis (25%) • Thumb anomalies other than hypoplasia/aplasia (triphalangeal thumb, symphalangism, duplica- Fig. 5.1. Patient 1, newborn. Antimongoloid slanting of palpe- tion, syndactyly between thumb and index ﬁnger) bral ﬁssures, severe micrognathia, low-set and dysmorphic • Carpal fusions ears Acrofacial Dysostosis, Nager Type 589

Fig. 5.2. Patient 2, newborn. There are malar hypoplasia and Fig. 5.3. Patient 2, newborn. Anomalies in the number of the severe micrognathia. The skull is disproportionately large rel- ribs can be seen (11 on left, 10 ribs on right side). Note also ative to the facial bones 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 590 Acrofacial Dysostosis, Nager Type

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)

a b

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 dysostosis syndrome: report of four patients with Nager syndrome 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): evidence 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 syndrome) associated with an inherited and apparently bal- anced X;9 translocation: prenatal and postnatal late repli- Fig. 5.6. Patient 2, newborn. The great toe is markedly short cation studies. Am J Med Genet 1993; 46: 379–83 and wide, with severe hypoplasia of the distal phalanx. The phalanges of the remaining toes are either hypoplastic or absent