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Rubinstein-Taybi syndrome due to EP300 haploinsufficiency(RSTS2)

MedGen UID:
462291
Concept ID:
C3150941
Disease or Syndrome
Synonyms: EP300-Related Rubinstein-Taybi Syndrome; Rubinstein-Taybi syndrome 2
 
Gene (location): EP300 (22q13.2)
 
Monarch Initiative: MONDO:0013364
OMIM®: 613684
Orphanet: ORPHA353284

Disease characteristics

Excerpted from the GeneReview: Rubinstein-Taybi Syndrome
Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and halluces, short stature, and moderate-to-severe intellectual disability. The characteristic craniofacial features are downslanted palpebral fissures, low-hanging columella, high palate, grimacing smile, and talon cusps. Prenatal growth is often normal, then height, weight, and head circumference percentiles rapidly drop in the first few months of life. Short stature is typical in adulthood. Obesity may develop in childhood or adolescence. Average IQ ranges between 35 and 50; however, developmental outcome varies considerably. Some individuals with EP300-RSTS have normal intellect. Additional features include ocular abnormalities, hearing loss, respiratory difficulties, congenital heart defects, renal abnormalities, cryptorchidism, feeding problems, recurrent infections, and severe constipation. [from GeneReviews]
Authors:
Cathy A Stevens   view full author information

Additional descriptions

From OMIM
Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomaly syndrome characterized by mental retardation, postnatal growth deficiency, microcephaly, broad thumbs and halluces, and dysmorphic facial features. The classic facial appearance is striking, with highly arched eyebrows, long eyelashes, downslanting palpebral fissures, broad nasal bridge, beaked nose with the nasal septum, highly arched palate, mild micrognathia, and characteristic grimacing or abnormal smile (Rubinstein and Taybi, 1963; review by Hennekam, 2006). About 50 to 70% of patients have RSTS1 (180849), caused by mutation in the CREBBP gene (600140). RSTS2 is much less common, and about 3% of patients have mutations in the EP300 gene. RSTS2 appears to be associated with a milder phenotype than RSTS1. Patients with RSTS2 have less severe facial dysmorphism and better cognitive function, but may have more severe microcephaly and malformation of facial bone structures compared to those with RSTS1 (Bartsch et al., 2010). For a discussion of genetic heterogeneity of Rubinstein-Taybi syndrome, see RSTS1 (180849).  http://www.omim.org/entry/613684
From MedlinePlus Genetics
Rubinstein-Taybi syndrome is a condition characterized by short stature, moderate to severe intellectual disability, distinctive facial features, and broad thumbs and first toes. Additional features of the disorder can include eye abnormalities, heart and kidney defects, dental problems, and obesity. These signs and symptoms vary among affected individuals. People with this condition have an increased risk of developing particular types of noncancerous brain and skin tumors.  https://medlineplus.gov/genetics/condition/rubinstein-taybi-syndrome

Clinical features

From HPO
Carious teeth
MedGen UID:
8288
Concept ID:
C0011334
Disease or Syndrome
Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Disease or Syndrome
Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).
Dental malocclusion
MedGen UID:
9869
Concept ID:
C0024636
Anatomical Abnormality
Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Preeclampsia
MedGen UID:
18608
Concept ID:
C0032914
Pathologic Function
Preeclampsia is a complication of pregnancy in which affected women develop high blood pressure (hypertension); they can also have abnormally high levels of protein in their urine (proteinuria). This condition usually occurs in the last few months of pregnancy and often requires early delivery of the infant. However, this condition can also appear shortly after giving birth (postpartum preeclampsia).\n\nMany women with mild preeclampsia do not feel ill, and the condition is often first detected through blood pressure and urine testing in their doctor's office. In addition to hypertension and proteinuria, signs and symptoms of preeclampsia can include excessive swelling (edema) of the face or hands and a weight gain of more than 3 to 5 pounds in a week due to fluid retention. Affected women may also experience headaches, dizziness, irritability, shortness of breath, a decrease in urination, upper abdominal pain, and nausea or vomiting. Vision changes may develop, including flashing lights or spots, increased sensitivity to light (photophobia), blurry vision, or temporary blindness.\n\nIn many cases, symptoms of preeclampsia go away within a few days after the baby is born. In severe cases, however, preeclampsia can damage the mother's organs, such as the heart, liver, and kidneys, and can lead to life-threatening complications. Extremely high blood pressure in the mother can cause bleeding in the brain (hemorrhagic stroke). The effects of high blood pressure on the brain (hypertensive encephalopathy) may also result in seizures. If seizures occur, the condition is considered to have worsened to eclampsia, which can result in coma. About 1 in 200 women with untreated preeclampsia develop eclampsia. Eclampsia can also develop without any obvious signs of preeclampsia.\n\nBetween 10 and 20 percent of women with severe preeclampsia develop another potentially life-threatening complication called HELLP syndrome. HELLP stands for hemolysis (premature red blood cell breakdown), elevated liver enzyme levels, and low platelets (cells involved in blood clotting), which are the key features of this condition.\n\nWomen who have had preeclampsia have approximately twice the lifetime risk of heart disease and stroke than do women in the general population. Researchers suggest that preeclampsia, heart disease, and stroke may share common risk factors. Women who have diseases such as obesity, hypertension, heart disease, diabetes, or kidney disease before they become pregnant have an increased risk of developing preeclampsia. Preeclampsia is most likely to occur in a woman's first pregnancy, although it can occur in subsequent pregnancies, particularly in women with other health conditions.\n\nSevere preeclampsia can also affect the fetus, with impairment of blood and oxygen flow leading to growth problems or stillbirth. Infants delivered early due to preeclampsia may have complications associated with prematurity, such as breathing problems caused by underdeveloped lungs.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Syndactyly
MedGen UID:
52619
Concept ID:
C0039075
Congenital Abnormality
Webbing or fusion of the fingers or toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers or toes in a proximo-distal axis are referred to as "symphalangism".
Intestinal malrotation
MedGen UID:
113153
Concept ID:
C0221210
Congenital Abnormality
An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Convex nasal ridge
MedGen UID:
66809
Concept ID:
C0240538
Finding
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Increased overbite
MedGen UID:
539656
Concept ID:
C0266063
Disease or Syndrome
Maxillary teeth cover the mandibular teeth when biting to an increased degree. The feature is defined as a vertical overlap of the maxillary incisors over the mandibular incisors that exceeds 2 mm.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Talon cusp
MedGen UID:
140772
Concept ID:
C0399357
Anatomical Abnormality
Talon cusp is an accessory cusp located near the cingulum (the portion of the lingual or palatal aspect of the tooth that forms a convex protuberance at the cervical third of the anatomic crown).
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a state of constantly being unusually or abnormally active, including in situations in which it is not appropriate.
Prominent nose
MedGen UID:
98423
Concept ID:
C0426415
Finding
Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.
Broad thumb
MedGen UID:
140880
Concept ID:
C0426891
Finding
Increased thumb width without increased dorso-ventral dimension.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Narrow palate
MedGen UID:
278045
Concept ID:
C1398312
Finding
Width of the palate more than 2 SD below the mean (objective) or apparently decreased palatal width (subjective).
Prominent fingertip pads
MedGen UID:
322758
Concept ID:
C1835807
Finding
A soft tissue prominence of the ventral aspects of the fingertips. The term "persistent fetal fingertip pads" is often used as a synonym, but should better not be used because it implies knowledge of history of the patient which often does not exist.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Short first metatarsal
MedGen UID:
330663
Concept ID:
C1841688
Finding
Short first metatarsal bone.
Thick eyebrow
MedGen UID:
377914
Concept ID:
C1853487
Finding
Increased density/number and/or increased diameter of eyebrow hairs.
Long eyelashes
MedGen UID:
342955
Concept ID:
C1853738
Finding
Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective).
Low hanging columella
MedGen UID:
344656
Concept ID:
C1856119
Finding
Columella extending inferior to the level of the nasal base, when viewed from the side.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Broad hallux
MedGen UID:
401165
Concept ID:
C1867131
Finding
Visible increase in width of the hallux without an increase in the dorso-ventral dimension.
Highly arched eyebrow
MedGen UID:
358357
Concept ID:
C1868571
Finding
Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape.
Short 5th toe
MedGen UID:
866760
Concept ID:
C4021111
Anatomical Abnormality
Underdevelopment (hypoplasia) of the fifth toe.
Posterior helix pit
MedGen UID:
867181
Concept ID:
C4021539
Finding
Permanent indentation on the posteromedial aspect of the helix that may be sharply or indistinctly delineated.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Rubinstein-Taybi syndrome due to EP300 haploinsufficiency in Orphanet.

Recent clinical studies

Etiology

Cohen JL, Schrier Vergano SA, Mazzola S, Strong A, Keena B, McDougall C, Ritter A, Li D, Bedoukian EC, Burke LW, Hoffman A, Zurcher V, Krantz ID, Izumi K, Bhoj E, Zackai EH, Deardorff MA
Am J Med Genet A 2020 Dec;182(12):2926-2938. Epub 2020 Oct 11 doi: 10.1002/ajmg.a.61883. PMID: 33043588

Diagnosis

Cohen JL, Schrier Vergano SA, Mazzola S, Strong A, Keena B, McDougall C, Ritter A, Li D, Bedoukian EC, Burke LW, Hoffman A, Zurcher V, Krantz ID, Izumi K, Bhoj E, Zackai EH, Deardorff MA
Am J Med Genet A 2020 Dec;182(12):2926-2938. Epub 2020 Oct 11 doi: 10.1002/ajmg.a.61883. PMID: 33043588
Lavery WJ, Barski A, Wiley S, Schorry EK, Lindsley AW
Clin Epigenetics 2020 Jan 10;12(1):10. doi: 10.1186/s13148-019-0802-2. PMID: 31924266Free PMC Article
Negri G, Magini P, Milani D, Crippa M, Biamino E, Piccione M, Sotgiu S, Perrìa C, Vitiello G, Frontali M, Boni A, Di Fede E, Gandini MC, Colombo EA, Bamshad MJ, Nickerson DA, Smith JD, Loddo I, Finelli P, Seri M, Pippucci T, Larizza L, Gervasini C
Hum Genet 2019 Mar;138(3):257-269. Epub 2019 Feb 26 doi: 10.1007/s00439-019-01985-y. PMID: 30806792Free PMC Article
Hamilton MJ, Newbury-Ecob R, Holder-Espinasse M, Yau S, Lillis S, Hurst JA, Clement E, Reardon W, Joss S, Hobson E, Blyth M, Al-Shehhi M, Lynch SA, Suri M; DDD Study
Clin Dysmorphol 2016 Oct;25(4):135-45. doi: 10.1097/MCD.0000000000000143. PMID: 27465822

Prognosis

Cohen JL, Schrier Vergano SA, Mazzola S, Strong A, Keena B, McDougall C, Ritter A, Li D, Bedoukian EC, Burke LW, Hoffman A, Zurcher V, Krantz ID, Izumi K, Bhoj E, Zackai EH, Deardorff MA
Am J Med Genet A 2020 Dec;182(12):2926-2938. Epub 2020 Oct 11 doi: 10.1002/ajmg.a.61883. PMID: 33043588
Negri G, Magini P, Milani D, Crippa M, Biamino E, Piccione M, Sotgiu S, Perrìa C, Vitiello G, Frontali M, Boni A, Di Fede E, Gandini MC, Colombo EA, Bamshad MJ, Nickerson DA, Smith JD, Loddo I, Finelli P, Seri M, Pippucci T, Larizza L, Gervasini C
Hum Genet 2019 Mar;138(3):257-269. Epub 2019 Feb 26 doi: 10.1007/s00439-019-01985-y. PMID: 30806792Free PMC Article
Hamilton MJ, Newbury-Ecob R, Holder-Espinasse M, Yau S, Lillis S, Hurst JA, Clement E, Reardon W, Joss S, Hobson E, Blyth M, Al-Shehhi M, Lynch SA, Suri M; DDD Study
Clin Dysmorphol 2016 Oct;25(4):135-45. doi: 10.1097/MCD.0000000000000143. PMID: 27465822

Clinical prediction guides

Negri G, Magini P, Milani D, Crippa M, Biamino E, Piccione M, Sotgiu S, Perrìa C, Vitiello G, Frontali M, Boni A, Di Fede E, Gandini MC, Colombo EA, Bamshad MJ, Nickerson DA, Smith JD, Loddo I, Finelli P, Seri M, Pippucci T, Larizza L, Gervasini C
Hum Genet 2019 Mar;138(3):257-269. Epub 2019 Feb 26 doi: 10.1007/s00439-019-01985-y. PMID: 30806792Free PMC Article
Hamilton MJ, Newbury-Ecob R, Holder-Espinasse M, Yau S, Lillis S, Hurst JA, Clement E, Reardon W, Joss S, Hobson E, Blyth M, Al-Shehhi M, Lynch SA, Suri M; DDD Study
Clin Dysmorphol 2016 Oct;25(4):135-45. doi: 10.1097/MCD.0000000000000143. PMID: 27465822
Lopez-Atalaya JP, Gervasini C, Mottadelli F, Spena S, Piccione M, Scarano G, Selicorni A, Barco A, Larizza L
J Med Genet 2012 Jan;49(1):66-74. Epub 2011 Oct 7 doi: 10.1136/jmedgenet-2011-100354. PMID: 21984751

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