Apert syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: ACS II, INCLUDED
VOGT CEPHALODACTYLY, INCLUDED
ACROCEPHALOSYNDACTYLY, TYPE II, INCLUDED
ACROCEPHALOSYNDACTYLY, TYPE I
ACS I APERT-CROUZON DISEASE, INCLUDED
ACS1
Acrocephalosyndactyly type 1
Number of Symptoms 109
OrphanetNr: 87
OMIM Id: 101200
ICD-10: Q87.0
UMLs: C0001193
MeSH: D000168
MedDRA: 10002943
Snomed: 205258009

Prevalence, inheritance and age of onset:

Prevalence: 1.25 of 100 000 [Orphanet]
Inheritance: Autosomal dominant
[Orphanet]
Age of onset: Antenatal
Neonatal
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Acrocephalosyndactyly
 -Rare bone disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Craniostenosis associated with a strabismus
 -Rare eye disease
 -Rare genetic disease
Pierre Robin syndrome associated with bone disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare maxillo-facial surgical disease
 -Rare otorhinolaryngologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000028) Cryptorchidism 347 / 7739
2
 (HPO:0000126) Hydronephrosis 119 / 7739
3
 (HPO:0000148) Vaginal atresia 16 / 7739
4
 (HPO:0012226) Ovarian teratoma Occasional [Orphanet] 2 / 7739
5
 (HPO:0000316) Hypertelorism Frequent [Orphanet] 644 / 7739
6
 (HPO:0000244) Brachyturricephaly 9 / 7739
7
 (HPO:0000327) Hypoplasia of the maxilla Very frequent [Orphanet] 129 / 7739
8
 (HPO:0004487) Acrobrachycephaly 1 / 7739
9
 (HPO:0000689) Dental malocclusion 114 / 7739
10
 (HPO:0002705) High, narrow palate Frequent [Orphanet] 308 / 7739
11
 (HPO:0007291) Posterior fossa cyst 10 / 7739
12
 (HPO:0000189) Narrow palate 45 / 7739
13
 (HPO:0010650) Hypoplasia of the premaxilla Frequent [Orphanet] 39 / 7739
14
 (HPO:0004440) Coronal craniosynostosis 38 / 7739
15
 (HPO:0000239) Large fontanelles Frequent [Orphanet] 135 / 7739
16
 (HPO:0012368) Flat face Very frequent [Orphanet] 106 / 7739
17
 (HPO:0000262) Turricephaly Very frequent [Orphanet] 38 / 7739
18
 (HPO:0002676) Cloverleaf skull Occasional [Orphanet] 14 / 7739
19
 (HPO:0000175) Cleft palate 349 / 7739
20
 (HPO:0000444) Convex nasal ridge Frequent [Orphanet] 87 / 7739
21
 (HPO:0011800) Midface retrusion 221 / 7739
22
 (HPO:0000174) Abnormality of the palate Occasional [Orphanet] 298 / 7739
23
 (HPO:0005280) Depressed nasal bridge Very frequent [Orphanet] 381 / 7739
24
 (HPO:0000586) Shallow orbits 23 / 7739
25
 (HPO:0000348) High forehead 157 / 7739
26
 (HPO:0000272) Malar flattening 277 / 7739
27
 (HPO:0000337) Broad forehead 116 / 7739
28
 (HPO:0000684) Delayed eruption of teeth Frequent [Orphanet] 117 / 7739
29
 (HPO:0000453) Choanal atresia Occasional [Orphanet] 76 / 7739
30
 (HPO:0000520) Proptosis Very frequent [Orphanet] 192 / 7739
31
 (HPO:0000452) Choanal stenosis 23 / 7739
32
 (HPO:0011331) Hemifacial atrophy Frequent [Orphanet] 79 / 7739
33
 (HPO:0000270) Delayed cranial suture closure 33 / 7739
34
 (HPO:0000494) Downslanted palpebral fissures Frequent [Orphanet] 328 / 7739
35
 (HPO:0000248) Brachycephaly Very frequent [Orphanet] 222 / 7739
36
 (HPO:0000303) Mandibular prognathia Frequent [Orphanet] 179 / 7739
37
 (HPO:0000193) Bifid uvula 66 / 7739
38
 (HPO:0002007) Frontal bossing Very frequent [Orphanet] 366 / 7739
39
 (HPO:0000572) Visual loss Occasional [Orphanet] 272 / 7739
40
 (HPO:0000486) Strabismus Frequent [Orphanet] 576 / 7739
41
 (HPO:0000481) Abnormality of the cornea Occasional [Orphanet] 124 / 7739
42
 (HPO:0000407) Sensorineural hearing impairment Occasional [Orphanet] 524 / 7739
43
 (HPO:0000405) Conductive hearing impairment Very frequent [Orphanet] 164 / 7739
44
 (HPO:0011390) Morphological abnormality of the inner ear Frequent [Orphanet] 21 / 7739
45
 (HPO:0000389) Chronic otitis media 64 / 7739
46
 (HPO:0000365) Hearing impairment 539 / 7739
47
 (HPO:0001249) Intellectual disability 1089 / 7739
48
 (HPO:0006101) Finger syndactyly Very frequent [Orphanet] 198 / 7739
49
 (HPO:0003422) Vertebral segmentation defect Frequent [Orphanet] 95 / 7739
50
 (HPO:0001770) Toe syndactyly Very frequent [Orphanet] 149 / 7739
51
 (HPO:0008111) Broad distal hallux 3 / 7739
52
 (HPO:0003041) Humeroradial synostosis 19 / 7739
53
 (HPO:0009642) Broad distal phalanx of the thumb 4 / 7739
54
 (HPO:0008905) Rhizomelia Occasional [Orphanet] 85 / 7739
55
 (HPO:0010554) Cutaneous finger syndactyly 39 / 7739
56
 (HPO:0001177) Preaxial hand polydactyly Rare [HPO:probinson] 59 / 7739
57
 (HPO:0001162) Postaxial hand polydactyly Rare [HPO:probinson] 119 / 7739
58
 (HPO:0009601) Aplasia/Hypoplasia of the thumb Frequent [Orphanet] 80 / 7739
59
 (HPO:0001172) Abnormality of the thumb Frequent [Orphanet] 103 / 7739
60
 (HPO:0004635) Cervical C5/C6 vertebrae fusion 2 / 7739
61
 (HPO:0100258) Preaxial polydactyly 39 / 7739
62
 (HPO:0005048) Synostosis of carpal bones 39 / 7739
63
 (HPO:0100259) Postaxial polydactyly 85 / 7739
64
 (HPO:0001841) Preaxial foot polydactyly 24 / 7739
65
 (HPO:0001545) Anteriorly placed anus Occasional [Orphanet] 55 / 7739
66
 (HPO:0002577) Abnormality of the stomach Occasional [Orphanet] 84 / 7739
67
 (HPO:0002021) Pyloric stenosis 51 / 7739
68
 (HPO:0004397) Ectopic anus 2 / 7739
69
 (HPO:0002032) Esophageal atresia 19 / 7739
70
 (HPO:0004325) Decreased body weight Frequent [Orphanet] 492 / 7739
71
 (HPO:0001507) Growth abnormality 36 / 7739
72
 (HPO:0001061) Acne 33 / 7739
73
 (HPO:0002623) Overriding aorta 8 / 7739
74
 (HPO:0030680) Abnormality of cardiovascular system morphology Occasional [Orphanet] 355 / 7739
75
 (HPO:0001629) Ventricular septal defect 316 / 7739
76
 (HPO:0000822) Hypertension Frequent [Orphanet] 224 / 7739
77
 (HPO:0002093) Respiratory insufficiency Occasional [Orphanet] 410 / 7739
78
 (HPO:0004468) Anomalous tracheal cartilage 2 / 7739
79
 (OMIM) Moderate to severe acne 1 / 7739
80
 (HPO:0002119) Ventriculomegaly Occasional [Orphanet] 253 / 7739
81
 (HPO:0000006) Autosomal dominant inheritance 2518 / 7739
82
 (OMIM) Broad distal phalanx of thumb 1 / 7739
83
 (OMIM) Birth weight normal 14 / 7739
84
 (OMIM) Symmetric osseous and/or cutaneous syndactyly of feet 1 / 7739
85
 (OMIM) Abnormal semicircular canals 1 / 7739
86
 (HPO:0100702) Arachnoid cyst 15 / 7739
87
 (HPO:0007370) Aplasia/Hypoplasia of the corpus callosum Frequent [Orphanet] 180 / 7739
88
 (OMIM) Cervical vertebrae fusion, usually at C5 to C6 1 / 7739
89
 (OMIM) Choanal atresia or stenosis 3 / 7739
90
 (HPO:0012758) Neurodevelopmental delay Frequent [Orphanet] 949 / 7739
91
 (OMIM) Mental retardation, variable 7 / 7739
92
 (OMIM) Fusion of carpal bones, especially capitate and hamate 1 / 7739
93
 (HPO:0001331) Absent septum pellucidum 16 / 7739
94
 (OMIM) High, broad forehead 4 / 7739
95
 (OMIM) Posterior fossa arachnoid cyst 1 / 7739
96
 (OMIM) Jugular foraminal stenosis 1 / 7739
97
 (HPO:0007099) Arnold-Chiari type I malformation 18 / 7739
98
 (OMIM) Symmetric osseous and/or cutaneous syndactyly of hands 1 / 7739
99
 (HPO:0000238) Hydrocephalus Occasional [Orphanet] 278 / 7739
100
 (HPO:0012795) Abnormality of the optic disc Occasional [Orphanet] 187 / 7739
101
 (OMIM) Birth length normal 15 / 7739
102
 (OMIM) Deceleration of linear growth during childhood 1 / 7739
103
 (HPO:0001355) Megalencephaly 39 / 7739
104
 (HPO:0002308) Arnold-Chiari malformation Occasional [Orphanet] 42 / 7739
105
 (HPO:0001274) Agenesis of corpus callosum 142 / 7739
106
 (OMIM) Low-lying cerebellar tonsils 1 / 7739
107
 (OMIM) Late-closing fontanel 1 / 7739
108
 (OMIM) Single nail common to digits 2 to 4 1 / 7739
109
 (HPO:0007343) Limbic malformations 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Apert syndrome is a congenital disorder characterized primarily by craniosynostosis, midface hypoplasia, and syndactyly of the hands and feet with a tendency to fusion of bony structures. Most cases are sporadic, but autosomal dominant inheritance has been reported ...
Diagnosis OMIM - Prenatal Diagnosis

Leonard et al. (1982) made the prenatal diagnosis of Apert syndrome by fetoscopy.

Chang et al. (1998) excluded the diagnosis of Apert syndrome in the fetus of an affected woman with ...
Clinical Description OMIM Apert (1906) defined a syndrome comprising skull malformation characterized by acrocephaly of brachysphenocephalic type and syndactyly of the hands and feet with complete distal fusion with a tendency to fusion of bony structures. The hand, when all the ...
Genotype-Phenotype Correlations OMIM Park et al. (1995) reported 36 patients with Apert syndrome, 35 of whom were found to carry either the S252W or P253R mutation in the FGFR2 gene, with a frequency of 71% and 26% for these 2 mutations, ...
Molecular genetics OMIM In all 40 unrelated patients with Apert syndrome, Wilkie et al. (1995) identified 1 of 2 mutations in exon 7 of the FGFR2 gene: S252W (176943.0010) or P253R (176943.0011). The findings confirmed that Apert syndrome is allelic to ...
Population genetics OMIM Blank (1960) estimated the frequency of Apert syndrome to be 1 in 160,000 births.

Cohen et al. (1992) studied the birth prevalence of Apert syndrome in Denmark, Italy, Spain, and 4 areas of the United States. ...