Rett syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: AUTISM, DEMENTIA, ATAXIA, AND LOSS OF PURPOSEFUL HAND USE RETT SYNDROME, ZAPPELLA VARIANT, INCLUDED
RETT SYNDROME, ATYPICAL, INCLUDED
RETT SYNDROME, PRESERVED SPEECH VARIANT, INCLUDED
RTT
RTS
Number of Symptoms 66
OrphanetNr: 778
OMIM Id: 312750
ICD-10: F84.2
UMLs: C0035372
MeSH: D015518
MedDRA: 10039000
Snomed: 68618008

Prevalence, inheritance and age of onset:

Prevalence: 4 of 100 000 [Orphanet]
Inheritance: X-linked dominant
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Monogenic disease with epilepsy
 -Rare genetic disease
 -Rare neurologic disease
Motor stereotypies
 -Rare genetic disease
 -Rare neurologic disease
Rare pervasive developmental disorder
 -Rare genetic disease
 -Rare neurologic disease
X-linked syndromic intellectual deficit
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
(HPO:0002019) Constipation 194 / 7739
2
(HPO:0002093) Respiratory insufficiency Frequent [Orphanet] 410 / 7739
3
(HPO:0001608) Abnormality of the voice Very frequent [Orphanet] 126 / 7739
4
(HPO:0004322) Short stature 1232 / 7739
5
(HPO:0004325) Decreased body weight Frequent [Orphanet] 492 / 7739
6
(HPO:0004326) Cachexia 71 / 7739
7
(HPO:0005135) EKG: T-wave abnormalities 19 / 7739
8
(HPO:0005184) Prolonged QTc interval 5 / 7739
9
(HPO:0011675) Arrhythmia Occasional [Orphanet] 226 / 7739
10
(HPO:0003202) Skeletal muscle atrophy Occasional [Orphanet] 281 / 7739
11
(HPO:0001324) Muscle weakness Occasional [Orphanet] 859 / 7739
12
(HPO:0002270) Abnormality of the autonomic nervous system Occasional [Orphanet] 22 / 7739
13
(HPO:0002066) Gait ataxia Frequent [Orphanet] 327 / 7739
14
(HPO:0002078) Truncal ataxia 41 / 7739
15
(HPO:0001276) Hypertonia Frequent [Orphanet] 317 / 7739
16
(HPO:0001257) Spasticity 251 / 7739
17
(HPO:0004374) Hemiplegia/hemiparesis Occasional [Orphanet] 158 / 7739
18
(HPO:0010521) Gait apraxia 1 / 7739
19
(HPO:0001332) Dystonia Frequent [Orphanet] 197 / 7739
20
(HPO:0000708) Behavioral abnormality Very frequent [Orphanet] 212 / 7739
21
(HPO:0100851) Abnormal emotion/affect behavior Frequent [Orphanet] 85 / 7739
22
(HPO:0000729) Autistic behavior 27 / 7739
23
(HPO:0000717) Autism Frequent [Orphanet] 108 / 7739
24
(HPO:0003763) Bruxism 7 / 7739
25
(HPO:0002376) Developmental regression 74 / 7739
26
(HPO:0002333) Motor deterioration 7 / 7739
27
(HPO:0002187) Intellectual disability, profound 44 / 7739
28
(HPO:0100716) Self-injurious behavior Occasional [Orphanet] 43 / 7739
29
(HPO:0002360) Sleep disturbance Frequent [Orphanet] 113 / 7739
30
(HPO:0000733) Stereotypy Very frequent [Orphanet] 58 / 7739
31
(HPO:0100543) Cognitive impairment Very frequent [Orphanet] 230 / 7739
32
(HPO:0002167) Neurological speech impairment Very frequent [Orphanet] 308 / 7739
33
(HPO:0100022) Abnormality of movement Very frequent [Orphanet] 129 / 7739
34
(HPO:0001288) Gait disturbance Very frequent [Orphanet] 318 / 7739
35
(HPO:0001337) Tremor Frequent [Orphanet] 200 / 7739
36
(HPO:0002353) EEG abnormality 188 / 7739
37
(HPO:0001250) Seizures Very frequent [Orphanet] 1245 / 7739
38
(HPO:0001773) Short foot 86 / 7739
39
(HPO:0000929) Abnormality of the skull Very frequent [Orphanet] 53 / 7739
40
(HPO:0000252) Microcephaly Very frequent [Orphanet] 832 / 7739
41
(HPO:0005484) Postnatal microcephaly 32 / 7739
42
(HPO:0002808) Kyphosis Frequent [Orphanet] 289 / 7739
43
(HPO:0002650) Scoliosis Frequent [Orphanet] 705 / 7739
44
(HPO:0004349) Reduced bone mineral density Occasional [Orphanet] 165 / 7739
45
(HPO:0001387) Joint stiffness Occasional [Orphanet] 322 / 7739
46
(HPO:0002020) Gastroesophageal reflux 101 / 7739
47
(HPO:0002240) Hepatomegaly Occasional [Orphanet] 467 / 7739
48
(HPO:0000478) Abnormality of the eye Frequent [Orphanet] 126 / 7739
49
(HPO:0000164) Abnormality of the teeth 291 / 7739
50
(HPO:0002104) Apnea Occasional [Orphanet] 106 / 7739
51
(HPO:0002793) Abnormal pattern of respiration Occasional [Orphanet] 26 / 7739
52
(HPO:0004879) Intermittent hyperventilation 2 / 7739
53
(HPO:0002120) Cerebral cortical atrophy Frequent [Orphanet] 187 / 7739
54
(HPO:0001522) Death in infancy Occasional [Orphanet] 275 / 7739
55
(HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
56
(HPO:0001423) X-linked dominant inheritance 69 / 7739
57
(MedDRA:10006322) Breath holding 1 / 7739
58
(OMIM) Cold feet 2 / 7739
59
(OMIM) EEG abnormalities - slow waking background, intermittent rhythmical slowing (3-5Hz), epileptiform discharges 1 / 7739
60
(OMIM) Hand stereotypies (e.g., hand wringing) 1 / 7739
61
(OMIM) Normal birth head circumference 2 / 7739
62
(OMIM) Normal development until 6-18 months 1 / 7739
63
(OMIM) Periodic apnea while awake 1 / 7739
64
(OMIM) Reduction or loss of acquired skills (e.g., purposeful hand use, speech) 1 / 7739
65
(OMIM) T-wave abnormalities 1 / 7739
66
(OMIM) Vasomotor disturbance 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Rett syndrome is a neurodevelopmental disorder that occurs almost exclusively in females. It is characterized by arrested development between 6 and 18 months of age, regression of acquired skills, loss of speech, stereotypical movements (classically of the hands), ...
Diagnosis OMIM Hagberg and Skjeldal (1994) suggested a model of inclusion and exclusion criteria for the diagnosis of Rett syndrome that relaxed the international criteria originally drawn up in Vienna in September 1984. The new model permitted the diagnosis of ...
Clinical Description OMIM Rett (1966, 1977), a Viennese pediatrician, first described Rett syndrome after observing 2 girls who exhibited the same unusual behavior who happened to be seated next to each other in the waiting room.

Hagberg et al. ...

Genotype-Phenotype Correlations OMIM Zappella et al. (2001) noted that all MECP2 mutations found in PSV patients have been either missense or late truncating mutations. In particular, the 4 early truncating hotspot mutations, R168X (300005.0020), R255X (300005.0021), R270X (300005.0005), and R294X (300005.0011), ...
Molecular genetics OMIM - Exclusion of Linked Genes

Ferlini et al. (1990) excluded the synapsin I gene as the cause of RTT. Narayanan et al. (1998) excluded the M6b gene (300051), Wan and Francke (1998) excluded glutamate dehydrogenase-2 (GLUD2; ...

Population genetics OMIM Hagberg (1985) estimated the frequency of Rett syndrome to be about 1 in 15,000 in southwestern Sweden. Among girls aged 0 to 18 years in North Dakota, Burd et al. (1991) found the frequency of Rett syndrome to ...