Fraser syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: CRYPTOPHTHALMOS WITH OTHER MALFORMATIONS CRYPTOPHTHALMOS-SYNDACTYLY SYNDROME, INCLUDED
Cryptophthalmos-syndactyly syndrome
Number of Symptoms 113
OrphanetNr: 2052
OMIM Id: 219000
ICD-10: Q87.0
UMLs:
MeSH: D058497
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 0.2 of 100 000 [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Antenatal
Neonatal
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Cryptophthalmia
 -Rare eye disease
 -Rare genetic disease
Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
 -Rare genetic disease
Multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
 -Rare developmental defect during embryogenesis
Syndromic anorectal malformation
 -Rare abdominal surgical disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Syndromic developmental defect of the eye
 -Rare developmental defect during embryogenesis
 -Rare eye disease
 -Rare genetic disease
Syndromic genetic deafness
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare otorhinolaryngologic disease
Syndromic renal or urinary tract malformation
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare renal disease

Symptom Information: Sort by abundance 

1
 (HPO:0000047) Hypospadias Occasional [Orphanet] 250 / 7739
2
 (HPO:0000028) Cryptorchidism 347 / 7739
3
 (HPO:0000046) Scrotal hypoplasia Frequent [Orphanet] 54 / 7739
4
 (HPO:0000035) Abnormality of the testis Occasional [Orphanet] 296 / 7739
5
 (HPO:0000054) Micropenis Frequent [Orphanet] 257 / 7739
6
 (HPO:0000142) Abnormality of the vagina Frequent [Orphanet] 24 / 7739
7
 (HPO:0000089) Renal hypoplasia 78 / 7739
8
 (HPO:0008678) Renal hypoplasia/aplasia Very frequent [Orphanet] 127 / 7739
9
 (HPO:0000062) Ambiguous genitalia Frequent [Orphanet] 74 / 7739
10
 (HPO:0010458) Female pseudohermaphroditism Frequent [Orphanet] 17 / 7739
11
 (HPO:0000107) Renal cyst Very frequent [Orphanet] 126 / 7739
12
 (HPO:0000813) Bicornuate uterus 22 / 7739
13
 (HPO:0000057) Clitoromegaly 30 / 7739
14
 (HPO:0000130) Abnormality of the uterus Occasional [Orphanet] 86 / 7739
15
 (HPO:0000079) Abnormality of the urinary system Occasional [Orphanet] 88 / 7739
16
 (HPO:0000148) Vaginal atresia 16 / 7739
17
 (HPO:0001126) Cryptophthalmos 3 / 7739
18
 (HPO:0002223) Absent eyebrow 21 / 7739
19
 (HPO:0000316) Hypertelorism Frequent [Orphanet] 644 / 7739
20
 (HPO:0000678) Dental crowding 65 / 7739
21
 (HPO:0000183) Difficulty in tongue movements 4 / 7739
22
 (HPO:0000636) Upper eyelid coloboma 7 / 7739
23
 (HPO:0000452) Choanal stenosis 23 / 7739
24
 (HPO:0009553) Abnormality of the hairline Occasional [Orphanet] 30 / 7739
25
 (HPO:0002006) Facial cleft 25 / 7739
26
 (HPO:0000366) Abnormality of the nose Occasional [Orphanet] 56 / 7739
27
 (HPO:0004112) Midline nasal groove 1 / 7739
28
 (HPO:0002084) Encephalocele Occasional [Orphanet] 70 / 7739
29
 (HPO:0000430) Underdeveloped nasal alae Occasional [Orphanet] 90 / 7739
30
 (HPO:0000252) Microcephaly Occasional [Orphanet] 832 / 7739
31
 (HPO:0007633) Bilateral microphthalmos 13 / 7739
32
 (HPO:0000561) Absent eyelashes 18 / 7739
33
 (HPO:0010297) Bifid tongue Frequent [Orphanet] 17 / 7739
34
 (HPO:0005325) Extension of hair growth on temples to lateral eyebrow 1 / 7739
35
 (HPO:0000175) Cleft palate 349 / 7739
36
 (HPO:0003191) Cleft ala nasi 8 / 7739
37
 (HPO:0002705) High, narrow palate Occasional [Orphanet] 308 / 7739
38
 (HPO:0000528) Anophthalmia 42 / 7739
39
 (HPO:0005280) Depressed nasal bridge 381 / 7739
40
 (HPO:0000204) Cleft upper lip Occasional [Orphanet] 193 / 7739
41
 (HPO:0000202) Oral cleft Occasional [Orphanet] 120 / 7739
42
 (HPO:0000315) Abnormality of the orbital region Very frequent [Orphanet] 18 / 7739
43
 (HPO:0000689) Dental malocclusion 114 / 7739
44
 (HPO:0001362) Calvarial skull defect Occasional [Orphanet] 22 / 7739
45
 (HPO:0000445) Wide nose Frequent [Orphanet] 190 / 7739
46
 (HPO:0000164) Abnormality of the teeth Frequent [Orphanet] 291 / 7739
47
 (HPO:0000431) Wide nasal bridge 290 / 7739
48
 (HPO:0007993) Malformed lacrimal ducts 1 / 7739
49
 (HPO:0000618) Blindness 124 / 7739
50
 (HPO:0000632) Lacrimation abnormality Very frequent [Orphanet] 42 / 7739
51
 (HPO:0007957) Corneal opacity 84 / 7739
52
 (HPO:0008056) Aplasia/Hypoplasia affecting the eye Frequent [Orphanet] 142 / 7739
53
 (HPO:0000572) Visual loss Very frequent [Orphanet] 272 / 7739
54
 (HPO:0007925) Lacrimal duct aplasia 2 / 7739
55
 (HPO:0008772) Aplasia/Hypoplasia of the external ear Frequent [Orphanet] 67 / 7739
56
 (HPO:0008559) Hypoplastic superior helix 6 / 7739
57
 (HPO:0000405) Conductive hearing impairment Occasional [Orphanet] 164 / 7739
58
 (HPO:0000369) Low-set ears 372 / 7739
59
 (HPO:0000356) Abnormality of the outer ear 85 / 7739
60
 (HPO:0000372) Abnormality of the auditory canal Occasional [Orphanet] 49 / 7739
61
 (HPO:0008609) Morphological abnormality of the middle ear 2 / 7739
62
 (HPO:0000413) Atresia of the external auditory canal 32 / 7739
63
 (HPO:0000378) Cupped ear 34 / 7739
64
 (HPO:0000377) Abnormality of the pinna 111 / 7739
65
 (HPO:0004452) Abnormality of the middle ear ossicles Frequent [Orphanet] 26 / 7739
66
 (HPO:0000357) Abnormal location of ears Frequent [Orphanet] 328 / 7739
67
 (HPO:0001249) Intellectual disability 1089 / 7739
68
 (HPO:0006610) Wide intermamillary distance 46 / 7739
69
 (HPO:0004404) Abnormality of the nipple Occasional [Orphanet] 54 / 7739
70
 (HPO:0009767) Aplasia/Hypoplasia of the phalanges of the hand 5 / 7739
71
 (HPO:0009601) Aplasia/Hypoplasia of the thumb 80 / 7739
72
 (HPO:0003183) Wide pubic symphysis 5 / 7739
73
 (HPO:0001770) Toe syndactyly Frequent [Orphanet] 149 / 7739
74
 (HPO:0010554) Cutaneous finger syndactyly 39 / 7739
75
 (HPO:0011867) Abnormality of the wing of the ilium Frequent [Orphanet] 123 / 7739
76
 (HPO:0006714) Aplasia/Hypoplasia of the sternum 1 / 7739
77
 (HPO:0002475) Myelomeningocele Occasional [Orphanet] 29 / 7739
78
 (HPO:0003422) Vertebral segmentation defect Occasional [Orphanet] 95 / 7739
79
 (HPO:0001159) Syndactyly 140 / 7739
80
 (HPO:0006101) Finger syndactyly Very frequent [Orphanet] 198 / 7739
81
 (HPO:0001551) Abnormality of the umbilicus 4 / 7739
82
 (HPO:0001537) Umbilical hernia Occasional [Orphanet] 206 / 7739
83
 (HPO:0002023) Anal atresia Frequent [Orphanet] 135 / 7739
84
 (HPO:0001539) Omphalocele Occasional [Orphanet] 102 / 7739
85
 (HPO:0002244) Abnormality of the small intestine 12 / 7739
86
 (HPO:0001545) Anteriorly placed anus Occasional [Orphanet] 55 / 7739
87
 (HPO:0004378) Abnormality of the anus 34 / 7739
88
 (HPO:0001627) Abnormal heart morphology 19 / 7739
89
 (HPO:0030680) Abnormality of cardiovascular system morphology Occasional [Orphanet] 355 / 7739
90
 (HPO:0002089) Pulmonary hypoplasia 80 / 7739
91
 (HPO:0001602) Laryngeal stenosis Frequent [Orphanet] 21 / 7739
92
 (HPO:0001607) Subglottic stenosis 5 / 7739
93
 (HPO:0006703) Aplasia/Hypoplasia of the lungs Occasional [Orphanet] 79 / 7739
94
 (HPO:0008750) Laryngeal atresia 3 / 7739
95
 (HPO:0002777) Tracheal stenosis Occasional [Orphanet] 35 / 7739
96
 (HPO:0005950) Laryngeal web 5 / 7739
97
 (HPO:0002101) Abnormal lung lobation Occasional [Orphanet] 33 / 7739
98
 (HPO:0005352) Severe T-cell immunodeficiency 20 / 7739
99
 (HPO:0000777) Abnormality of the thymus 9 / 7739
100
 (OMIM) Absent or malformed lacrimal ducts 1 / 7739
101
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
102
 (HPO:0011420) Death Occasional [Orphanet] 184 / 7739
103
 (OMIM) Hypoplastic, notched nares 1 / 7739
104
 (HPO:0000238) Hydrocephalus 278 / 7739
105
 (OMIM) Umbilical anomaly 1 / 7739
106
 (OMIM) Unusual hairline 1 / 7739
107
 (OMIM) Teeth crowding 1 / 7739
108
 (OMIM) Broad, low nasal bridge 1 / 7739
109
 (OMIM) Diastasis of symphysis pubis 1 / 7739
110
 (OMIM) Midline nasal cleavage 1 / 7739
111
 (HPO:0012758) Neurodevelopmental delay Occasional [Orphanet] 949 / 7739
112
 (HPO:0002536) Abnormal cortical gyration 72 / 7739
113
 (HPO:0001522) Death in infancy Occasional [Orphanet] 275 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Diagnosis OMIM Koenig and Spranger (1986) noted that eye lesions are apparently nonobligatory components of the syndrome. The diagnosis of Fraser syndrome should be entertained in patients with a combination of acrofacial and urogenital malformations with or without cryptophthalmos. Thomas ...
Clinical Description OMIM In each of 2 sibships, Fraser (1962) observed 2 sisters affected at birth by various combinations: cryptophthalmos; absent or malformed lacrimal ducts; middle and outer ear malformations; high palate; cleavage along the midplane of nares and tongue; hypertelorism; ...
Molecular genetics OMIM - Mutation in the FRAS1 Gene on Chromosome 4q21

In 5 families with Fraser syndrome, McGregor et al. (2003) identified 5 homozygous mutations in the FRAS1 gene (e.g., 607830.0001), which encodes a putative extracellular matrix (ECM) ...