Nager syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: AFD, NAGER TYPE
MANDIBULOFACIAL DYSOSTOSIS, TREACHER COLLINS TYPE, WITH LIMB ANOMALIES
NAGER SYNDROME
AFD1
NAFD
Mandibulofacial dysostosis with preaxial limb anomalies
nager acrofacial dysostosis
Preaxial acrodysostosis
Number of Symptoms 86
OrphanetNr: 245
OMIM Id: 154400
ICD-10: Q75.4
UMLs: C0265245
MeSH: C538184
MedDRA:
Snomed: 35520007

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal dominant
Autosomal recessive
Not applicable
[Orphanet]
Age of onset: Antenatal
Neonatal
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Acrofacial dysostosis
 -Rare bone disease
 -Rare developmental defect during embryogenesis
Branchial arch or oral-acral syndrome
 -Rare developmental defect during embryogenesis
Genetic branchial arch or oral-acral syndrome
 -Rare genetic disease
Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
 -Rare genetic disease
Malposition of external canthus
 -Rare eye disease
 -Rare genetic disease
Multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
 -Rare developmental defect during embryogenesis
Pierre Robin syndrome associated with branchial archs anomalies
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare maxillo-facial surgical disease
 -Rare otorhinolaryngologic disease
Syndromic developmental defect of the eye
 -Rare developmental defect during embryogenesis
 -Rare eye disease
 -Rare genetic disease
Syndromic palpebral coloboma
 -Rare eye disease
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000625) Cleft eyelid Frequent [Orphanet] 31 / 7739
2
 (HPO:0000652) Lower eyelid coloboma 9 / 7739
3
 (HPO:0000508) Ptosis Frequent [Orphanet] 459 / 7739
4
 (HPO:0002093) Respiratory insufficiency Frequent [Orphanet] 410 / 7739
5
 (HPO:0005349) Hypoplasia of the epiglottis 7 / 7739
6
 (HPO:0008749) Laryngeal hypoplasia 5 / 7739
7
 (HPO:0004322) Short stature 1232 / 7739
8
 (HPO:0030680) Abnormality of cardiovascular system morphology Occasional [Orphanet] 355 / 7739
9
 (HPO:0001629) Ventricular septal defect rare [HPO:skoehler] 316 / 7739
10
 (HPO:0001643) Patent ductus arteriosus rare [HPO:skoehler] 228 / 7739
11
 (HPO:0001636) Tetralogy of Fallot 104 / 7739
12
 (HPO:0002251) Aganglionic megacolon 78 / 7739
13
 (HPO:0000750) Delayed speech and language development 197 / 7739
14
 (HPO:0002167) Neurological speech impairment Very frequent [Orphanet] 308 / 7739
15
 (HPO:0009601) Aplasia/Hypoplasia of the thumb Very frequent [Orphanet] 80 / 7739
16
 (HPO:0009777) Absent thumb 31 / 7739
17
 (HPO:0009466) Radial deviation of finger 101 / 7739
18
 (HPO:0010055) Broad hallux 56 / 7739
19
 (HPO:0001822) Hallux valgus 70 / 7739
20
 (HPO:0001849) Foot oligodactyly 9 / 7739
21
 (HPO:0001831) Short toe 52 / 7739
22
 (HPO:0001845) Overlapping toe 18 / 7739
23
 (HPO:0001770) Toe syndactyly 149 / 7739
24
 (HPO:0001159) Syndactyly 140 / 7739
25
 (HPO:0002814) Abnormality of the lower limb Occasional [Orphanet] 23 / 7739
26
 (HPO:0001762) Talipes equinovarus 309 / 7739
27
 (HPO:0002827) Hip dislocation 94 / 7739
28
 (HPO:0002818) Abnormality of the radius Frequent [Orphanet] 96 / 7739
29
 (HPO:0003974) Absent radius 26 / 7739
30
 (HPO:0002984) Hypoplasia of the radius 44 / 7739
31
 (HPO:0002974) Radioulnar synostosis Frequent [Orphanet] 52 / 7739
32
 (HPO:0009821) Forearm undergrowth 8 / 7739
33
 (HPO:0001199) Triphalangeal thumb Occasional [Orphanet] 56 / 7739
34
 (HPO:0001377) Limited elbow extension 38 / 7739
35
 (HPO:0009829) Phocomelia Occasional [Orphanet] 20 / 7739
36
 (HPO:0000277) Abnormality of the mandible Very frequent [Orphanet] 394 / 7739
37
 (HPO:0000347) Micrognathia 426 / 7739
38
 (HPO:0000278) Retrognathia 100 / 7739
39
 (HPO:0000211) Trismus 9 / 7739
40
 (HPO:0000327) Hypoplasia of the maxilla Very frequent [Orphanet] 129 / 7739
41
 (HPO:0000252) Microcephaly 832 / 7739
42
 (HPO:0006657) Hypoplasia of first ribs 3 / 7739
43
 (HPO:0003319) Abnormality of the cervical spine 6 / 7739
44
 (HPO:0002650) Scoliosis 705 / 7739
45
 (HPO:0001387) Joint stiffness Frequent [Orphanet] 322 / 7739
46
 (HPO:0002652) Skeletal dysplasia Very frequent [Orphanet] 113 / 7739
47
 (HPO:0007776) Sparse lower eyelashes 3 / 7739
48
 (HPO:0100840) Aplasia/Hypoplasia of the eyebrow Frequent [Orphanet] 117 / 7739
49
 (HPO:0200102) Sparse or absent eyelashes 64 / 7739
50
 (HPO:0001543) Gastroschisis 11 / 7739
51
 (HPO:0000813) Bicornuate uterus 22 / 7739
52
 (HPO:0000494) Downslanted palpebral fissures Very frequent [Orphanet] 328 / 7739
53
 (HPO:0000272) Malar flattening Very frequent [Orphanet] 277 / 7739
54
 (HPO:0011800) Midface retrusion 221 / 7739
55
 (HPO:0000174) Abnormality of the palate Frequent [Orphanet] 298 / 7739
56
 (HPO:0000220) Velopharyngeal insufficiency 10 / 7739
57
 (HPO:0000175) Cleft palate 349 / 7739
58
 (HPO:0000204) Cleft upper lip Occasional [Orphanet] 193 / 7739
59
 (HPO:0000154) Wide mouth Frequent [Orphanet] 137 / 7739
60
 (HPO:0005105) Abnormal nasal morphology Frequent [Orphanet] 114 / 7739
61
 (HPO:0000426) Prominent nasal bridge 121 / 7739
62
 (HPO:0000606) Abnormality of the periorbital region Frequent [Orphanet] 96 / 7739
63
 (HPO:0000405) Conductive hearing impairment 164 / 7739
64
 (HPO:0000384) Preauricular skin tag 62 / 7739
65
 (HPO:0000357) Abnormal location of ears Occasional [Orphanet] 328 / 7739
66
 (HPO:0000372) Abnormality of the auditory canal Frequent [Orphanet] 49 / 7739
67
 (HPO:0008772) Aplasia/Hypoplasia of the external ear Frequent [Orphanet] 67 / 7739
68
 (HPO:0000413) Atresia of the external auditory canal 32 / 7739
69
 (HPO:0000369) Low-set ears 372 / 7739
70
 (HPO:0000358) Posteriorly rotated ears 163 / 7739
71
 (HPO:0001025) Urticaria 73 / 7739
72
 (HPO:0008678) Renal hypoplasia/aplasia Occasional [Orphanet] 127 / 7739
73
 (HPO:0000122) Unilateral renal agenesis 24 / 7739
74
 (HPO:0000365) Hearing impairment Very frequent [Orphanet] 539 / 7739
75
 (HPO:0001622) Premature birth 100 / 7739
76
 (HPO:0002410) Aqueductal stenosis 19 / 7739
77
 (HPO:0000006) Autosomal dominant inheritance 2518 / 7739
78
 (HPO:0030084) Clinodactyly 90 / 7739
79
 (HPO:0000238) Hydrocephalus 278 / 7739
80
 (HPO:0002126) Polymicrogyria 64 / 7739
81
 (MedDRA:10058668) Clinodactyly 91 / 7739
82
 (MedDRA:10046752) Urticaria pigmentosa 3 / 7739
83
 (OMIM) Duplicated calyx 1 / 7739
84
 (OMIM) Hypoplastic zygomatic arch 1 / 7739
85
 (OMIM) Normal intelligence 81 / 7739
86
 (OMIM) Partial-total absence of lower eyelashes 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Nager syndrome is the prototype for a group of disorders collectively referred to as the acrofacial dysostoses (AFDs), which are characterized by malformation of the craniofacial skeleton and the limbs. The major facial features of Nager syndrome include ...
Diagnosis OMIM - Prenatal Diagnosis

Hecht et al. (1987) identified the Nager syndrome in a newborn infant and in a subsequent sib by prenatal ultrasonography. They presented this as evidence of autosomal recessive inheritance.
Clinical Description OMIM Nager acrofacial dysostosis was recognized as a specific entity by Nager and de Reynier (1948), but was probably first reported by Slingenberg (1908). The limb deformities in the Nager syndrome consist of absence of radius, radioulnar synostosis, and ...
Molecular genetics OMIM After exome sequencing in patients with the Nager type of acrofacial dysostosis pointed to SF3B4 (605593) as a strong candidate gene, Bernier et al. (2012) identified 18 different heterozygous SF3B4 mutations in 20 (57%) of 35 families affected ...