Rubinstein-Taybi syndrome due to CREBBP mutations

General Information (adopted from Orphanet):

Synonyms, Signs: BROAD THUMBS AND GREAT TOES, CHARACTERISTIC FACIES, AND MENTAL RETARDATION
BROAD THUMB-HALLUX SYNDROME
RUBINSTEIN SYNDROME
RSTS1
Number of Symptoms 148
OrphanetNr: 353277
OMIM Id: 180849
ICD-10: Q87.2
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal dominant inheritance
Heterogeneous
Sporadic
[Omim]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Rubinstein-Taybi syndrome
 -Rare bone disease
 -Rare developmental defect during embryogenesis
 -Rare endocrine disease
 -Rare eye disease
 -Rare genetic disease
 -Rare neurologic disease
 -Rare oncologic disease
 -Rare renal disease

Symptom Information: Sort by abundance 

1
 (HPO:0000028) Cryptorchidism 347 / 7739
2
 (HPO:0000077) Abnormality of the kidney 73 / 7739
3
 (HPO:0000049) Shawl scrotum 31 / 7739
4
 (HPO:0000136) Bifid uterus 6 / 7739
5
 (HPO:0009715) Papillary cystadenoma of the epididymis 3 / 7739
6
 (HPO:0000047) Hypospadias 250 / 7739
7
 (HPO:0000490) Deeply set eye 131 / 7739
8
 (HPO:0006483) Abnormal number of teeth 3 / 7739
9
 (HPO:0009765) Low hanging columella 9 / 7739
10
 (HPO:0000270) Delayed cranial suture closure 33 / 7739
11
 (HPO:0002700) Large foramen magnum 6 / 7739
12
 (HPO:0000218) High palate 356 / 7739
13
 (HPO:0000294) Low anterior hairline 52 / 7739
14
 (HPO:0002697) Parietal foramina 12 / 7739
15
 (HPO:0000260) Wide anterior fontanel 55 / 7739
16
 (HPO:0002553) Highly arched eyebrow 92 / 7739
17
 (HPO:0004411) Deviated nasal septum 3 / 7739
18
 (HPO:0000574) Thick eyebrow 96 / 7739
19
 (HPO:0000494) Downslanted palpebral fissures 328 / 7739
20
 (HPO:0002162) Low posterior hairline 88 / 7739
21
 (HPO:0000286) Epicanthus 371 / 7739
22
 (HPO:0000347) Micrognathia 426 / 7739
23
 (HPO:0000431) Wide nasal bridge 17942008 IBIS 290 / 7739
24
 (HPO:0000444) Convex nasal ridge 87 / 7739
25
 (HPO:0000527) Long eyelashes 46 / 7739
26
 (HPO:0011087) Talon cusp 2 / 7739
27
 (HPO:0000278) Retrognathia 100 / 7739
28
 (HPO:0002788) Recurrent upper respiratory tract infections 31 / 7739
29
 (HPO:0000327) Hypoplasia of the maxilla 129 / 7739
30
 (HPO:0000273) Facial grimacing 6 / 7739
31
 (HPO:0000678) Dental crowding 65 / 7739
32
 (HPO:0002007) Frontal bossing 366 / 7739
33
 (HPO:0000252) Microcephaly 832 / 7739
34
 (HPO:0000160) Narrow mouth 188 / 7739
35
 (HPO:0006297) Hypoplasia of dental enamel 64 / 7739
36
 (HPO:0000520) Proptosis 192 / 7739
37
 (HPO:0000689) Dental malocclusion 114 / 7739
38
 (HPO:0000189) Narrow palate 45 / 7739
39
 (HPO:0000486) Strabismus 576 / 7739
40
 (HPO:0009921) Duane anomaly 9 / 7739
41
 (HPO:0001135) Chorioretinal dystrophy 18 / 7739
42
 (HPO:0000539) Abnormality of refraction 6 / 7739
43
 (HPO:0000508) Ptosis 459 / 7739
44
 (HPO:0000501) Glaucoma 180 / 7739
45
 (HPO:0000589) Coloboma 47 / 7739
46
 (HPO:0000579) Nasolacrimal duct obstruction 9 / 7739
47
 (HPO:0000481) Abnormality of the cornea 124 / 7739
48
 (HPO:0000518) Cataract 454 / 7739
49
 (HPO:0000365) Hearing impairment 16868563 IBIS 539 / 7739
50
 (HPO:0000369) Low-set ears 372 / 7739
51
 (HPO:0000377) Abnormality of the pinna 111 / 7739
52
 (HPO:0002370) Poor coordination 15 / 7739
53
 (HPO:0000756) Agoraphobia 4 / 7739
54
 (HPO:0001335) Bimanual synkinesia 9 / 7739
55
 (HPO:0000750) Delayed speech and language development 197 / 7739
56
 (HPO:0000736) Short attention span 16 / 7739
57
 (HPO:0002183) Phonophobia 10 / 7739
58
 (HPO:0002317) Unsteady gait 45 / 7739
59
 (HPO:0000752) Hyperactivity 140 / 7739
60
 (HPO:0001249) Intellectual disability 1089 / 7739
61
 (HPO:0002353) EEG abnormality 188 / 7739
62
 (HPO:0001347) Hyperreflexia 363 / 7739
63
 (HPO:0000733) Stereotypy 58 / 7739
64
 (HPO:0000742) Self-mutilation 27 / 7739
65
 (HPO:0002870) Obstructive sleep apnea 16 / 7739
66
 (HPO:0100710) Impulsivity 16 / 7739
67
 (HPO:0000717) Autism 108 / 7739
68
 (HPO:0002251) Aganglionic megacolon 78 / 7739
69
 (HPO:0001250) Seizures 1245 / 7739
70
 (HPO:0010314) Premature thelarche 4 / 7739
71
 (HPO:0003319) Abnormality of the cervical spine 6 / 7739
72
 (HPO:0002650) Scoliosis 705 / 7739
73
 (HPO:0000954) Single transverse palmar crease 162 / 7739
74
 (HPO:0000766) Abnormality of the sternum 31 / 7739
75
 (HPO:0002999) Patellar dislocation 46 / 7739
76
 (HPO:0005743) Avascular necrosis of the capital femoral epiphysis 17 / 7739
77
 (HPO:0000767) Pectus excavatum 244 / 7739
78
 (HPO:0010055) Broad hallux 56 / 7739
79
 (HPO:0004209) Clinodactyly of the 5th finger 288 / 7739
80
 (HPO:0001382) Joint hypermobility 231 / 7739
81
 (HPO:0001371) Flexion contracture 220 / 7739
82
 (HPO:0001212) Prominent fingertip pads 12 / 7739
83
 (HPO:0002869) Flared iliac wings 20 / 7739
84
 (HPO:0001388) Joint laxity 117 / 7739
85
 (HPO:0003298) Spina bifida occulta 67 / 7739
86
 (HPO:0002866) Hypoplastic iliac wing 34 / 7739
87
 (HPO:0005895) Radial deviation of thumb terminal phalanx 3 / 7739
88
 (HPO:0011304) Broad thumb 39 / 7739
89
 (HPO:0010066) Duplication of phalanx of hallux 9 / 7739
90
 (HPO:0003083) Dislocated radial head 35 / 7739
91
 (HPO:0001159) Syndactyly 140 / 7739
92
 (HPO:0001763) Pes planus 176 / 7739
93
 (HPO:0001042) High axial triradius 4 / 7739
94
 (HPO:0010442) Polydactyly 69 / 7739
95
 (HPO:0002750) Delayed skeletal maturation 250 / 7739
96
 (HPO:0001561) Polyhydramnios 16868563 IBIS 191 / 7739
97
 (HPO:0008872) Feeding difficulties in infancy 153 / 7739
98
 (HPO:0002019) Constipation 194 / 7739
99
 (HPO:0001956) Truncal obesity 39 / 7739
100
 (HPO:0008897) Postnatal growth retardation 113 / 7739
101
 (HPO:0001508) Failure to thrive 454 / 7739
102
 (HPO:0004322) Short stature 1232 / 7739
103
 (HPO:0005306) Capillary hemangiomas 8 / 7739
104
 (HPO:0010562) Keloids 11 / 7739
105
 (HPO:0008107) Plantar crease between first and second toes 1 / 7739
106
 (HPO:0002236) Frontal upsweep of hair 8 / 7739
107
 (HPO:0001007) Hirsutism 91 / 7739
108
 (HPO:0000957) Cafe-au-lait spot 84 / 7739
109
 (HPO:0001643) Patent ductus arteriosus 228 / 7739
110
 (HPO:0001671) Abnormality of the cardiac septa 55 / 7739
111
 (HPO:0011675) Arrhythmia 226 / 7739
112
 (HPO:0010775) Vascular ring 3 / 7739
113
 (HPO:0001629) Ventricular septal defect 316 / 7739
114
 (HPO:0001631) Atria septal defect 274 / 7739
115
 (HPO:0002205) Recurrent respiratory infections 254 / 7739
116
 (HPO:0001601) Laryngomalacia 61 / 7739
117
 (HPO:0002880) Respiratory difficulties 15 / 7739
118
 (HPO:0002719) Recurrent infections 107 / 7739
119
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
120
 (HPO:0001324) Muscle weakness 859 / 7739
121
 (HPO:0010547) Muscle flaccidity 466 / 7739
122
 (HPO:0001252) Muscular hypotonia 990 / 7739
123
 (OMIM) Small opening of the mouth 1 / 7739
124
 (OMIM) Labile mood 2 / 7739
125
 (OMIM) Increased risk of leukemia 3 / 7739
126
 (HPO:0002144) Tethered cord 8 / 7739
127
 (OMIM) Screwdriver permanent incisors 1 / 7739
128
 (OMIM) Polysaccharide antibody response defect 1 / 7739
129
 (OMIM) Small, flared iliac wings 2 / 7739
130
 (OMIM) Keloid formation in surgical scars 1 / 7739
131
 (OMIM) Severe expressive speech delay 1 / 7739
132
 (OMIM) Crossbite 1 / 7739
133
 (OMIM) Increased risk of tumor formation, especially of the head 1 / 7739
134
 (OMIM) Broad thumbs with radial angulation 1 / 7739
135
 (OMIM) A small minority of patients have translocations and inversions involving 16p13.3 1 / 7739
136
 (HPO:0001274) Agenesis of corpus callosum 142 / 7739
137
 (HPO:0003745) Sporadic 131 / 7739
138
 (OMIM) Average adult female height 147 cm 1 / 7739
139
 (HPO:0000006) Autosomal dominant inheritance 2518 / 7739
140
 (HPO:0003828) Variable expressivity 130 / 7739
141
 (HPO:0001425) Heterogeneous 132 / 7739
142
 (OMIM) Average adult male height 153 cm 1 / 7739
143
 (OMIM) Ten percent of cases are secondary to submicroscopic deletions of 16p13.3 detectable by FISH 1 / 7739
144
 (OMIM) Grimacing or unusual smile with almost closing of the eyes 1 / 7739
145
 (OMIM) Obesity after puberty 1 / 7739
146
 (OMIM) Enamel discoloration 1 / 7739
147
 (OMIM) Otitis, recurrent 7 / 7739
148
 (OMIM) Good social contacts 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Rubinstein-Taybi syndrome is a multiple congenital anomaly syndrome characterized by mental retardation, postnatal growth deficiency, microcephaly, broad thumbs and halluces, and dysmorphic facial features. The facial appearance is striking, with highly arched eyebrows, long eyelashes, downslanting palpebral fissures, ...
Diagnosis OMIM Wallerstein et al. (1997) used the RT1 probe to screen 64 patients with clinical evidence of RSTS; 7 (11%) had a deletion. Another patient had a translocation involving the region without evidence of deletion. The features of coloboma, ...
Clinical Description OMIM Rubinstein and Taybi (1963) reported a syndrome characterized by mental retardation, broad thumbs and toes, and facial abnormalities. Rubinstein (1969) found parental age to be about average. Levy (1976) described juvenile glaucoma in RSTS and McKusick (1968) observed ...
Genotype-Phenotype Correlations OMIM Using FISH and 3 cosmid probes, Bartsch et al. (1999) studied 45 Rubinstein-Taybi syndrome patients from Germany, the Czech Republic, Austria, and Turkey and found 4 deletions. This gave a frequency of deletions of 8.9%; when pooled with ...
Molecular genetics OMIM Petrij et al. (1995) showed that the breakpoints at 16p13.3 demonstrated in patients with RSTS are all restricted to a region that contains the gene for the human CREB-binding protein (CREBBP; 600140), a nuclear protein participating as a ...
Population genetics OMIM Padfield et al. (1968) estimated that the frequency of Rubinstein syndrome was 1 per 300-500 in institutionalized patients with mental retardation over age 5 years.