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Temple-Baraitser syndrome(TMBTS)

MedGen UID:
395636
Concept ID:
C2678486
Congenital Abnormality; Disease or Syndrome
Synonyms: Severe mental retardation and absent nails of hallux and pollex; TMBTS
SNOMED CT: Temple Baraitser syndrome (725140007); Severe intellectual disability, hypoplasia of thumb and hallux syndrome (725140007)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): KCNH1 (1q32.2)
 
Monarch Initiative: MONDO:0012735
OMIM®: 611816
Orphanet: ORPHA420561

Definition

Temple-Baraitser syndrome is a rare developmental disorder characterized by severe mental retardation and anomalies of the first ray of the upper and lower limbs with absence/hypoplasia of the nails. Most patients also have seizures; various dysmorphic facial features have been reported (summary by Jacquinet et al., 2010). [from OMIM]

Clinical features

From HPO
Broad thumb
MedGen UID:
140880
Concept ID:
C0426891
Finding
Increased thumb width without increased dorso-ventral dimension.
Thumbs, congenital Clasped
MedGen UID:
98140
Concept ID:
C0431886
Congenital Abnormality
In the resting position, the tip of the thumb is on, or near, the palm, close to the base of the fourth or fifth finger.
Short distal phalanx of finger
MedGen UID:
326590
Concept ID:
C1839829
Finding
Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.
Long hallux
MedGen UID:
400514
Concept ID:
C1864375
Finding
Increased length of the big toe.
Proximal placement of thumb
MedGen UID:
356033
Concept ID:
C1865572
Finding
Proximal mislocalization of the thumb.
Broad hallux
MedGen UID:
401165
Concept ID:
C1867131
Finding
Visible increase in width of the hallux without an increase in the dorso-ventral dimension.
Pseudoepiphysis of the thumb
MedGen UID:
765398
Concept ID:
C3552484
Finding
A pseudoepiphysis (which is a secondary ossification center distinct from the normal epiphysis) of one or more phalanges of the thumb.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
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.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Wide mouth
MedGen UID:
44238
Concept ID:
C0024433
Congenital Abnormality
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
Myopathic facies
MedGen UID:
90695
Concept ID:
C0332615
Finding
A facial appearance characteristic of myopathic conditions. The face appears expressionless with sunken cheeks, bilateral ptosis, and inability to elevate the corners of the mouth, due to muscle weakness.
Wide nose
MedGen UID:
140869
Concept ID:
C0426421
Finding
Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae.
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).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Thick vermilion border
MedGen UID:
332232
Concept ID:
C1836543
Finding
Increased width of the skin of vermilion border region of upper lip.
Thick nasal alae
MedGen UID:
335032
Concept ID:
C1844809
Finding
Increase in bulk of the ala nasi.
Short columella
MedGen UID:
341783
Concept ID:
C1857479
Finding
Reduced distance from the anterior border of the naris to the subnasale.
Flat forehead
MedGen UID:
347463
Concept ID:
C1857485
Finding
A forehead with abnormal flatness.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Downturned corners of mouth
MedGen UID:
356471
Concept ID:
C1866195
Anatomical Abnormality
A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure.
Absent nail of hallux
MedGen UID:
866734
Concept ID:
C4021081
Anatomical Abnormality
Absent nail of big toe.
Absent thumbnail
MedGen UID:
868455
Concept ID:
C4022849
Finding
Absence of thumb nail.
Hypoplastic thumbnail
MedGen UID:
868456
Concept ID:
C4022850
Anatomical Abnormality
A thumbnail that is diminished in length and width, i.e., underdeveloped thumb nail.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVTemple-Baraitser syndrome

Professional guidelines

PubMed

Tian MQ, Li RK, Yang F, Shu XM, Li J, Chen J, Peng LY, Yu XH, Yang CJ
CNS Neurosci Ther 2023 Jan;29(1):270-281. Epub 2022 Oct 25 doi: 10.1111/cns.14001. PMID: 36285361Free PMC Article

Recent clinical studies

Etiology

Napoli G, Panzironi N, Traversa A, Catalanotto C, Pace V, Petrizzelli F, Giovannetti A, Lazzari S, Cogoni C, Tartaglia M, Carella M, Mazza T, Pizzuti A, Parisi C, Caputo V
Mol Neurobiol 2022 Aug;59(8):4825-4838. Epub 2022 May 31 doi: 10.1007/s12035-022-02886-4. PMID: 35639255Free PMC Article
Rühl P, Langner JM, Reidel J, Schönherr R, Hoshi T, Heinemann SH
Commun Biol 2021 Oct 7;4(1):1164. doi: 10.1038/s42003-021-02675-0. PMID: 34620975Free PMC Article
Hara-Isono K, Matsubara K, Fuke T, Yamazawa K, Satou K, Murakami N, Saitoh S, Nakabayashi K, Hata K, Ogata T, Fukami M, Kagami M
Clin Epigenetics 2020 Oct 22;12(1):159. doi: 10.1186/s13148-020-00949-8. PMID: 33092629Free PMC Article
Hamilton MJ, Suri M
Adv Genet 2020;105:137-174. Epub 2020 May 26 doi: 10.1016/bs.adgen.2020.03.002. PMID: 32560786
Severi G, Bernardini L, Briuglia S, Bigoni S, Buldrini B, Magini P, Dentici ML, Cordelli DM, Arrigo T, Franzoni E, Fini S, Italyankina E, Loddo I, Novelli A, Graziano C
Am J Med Genet A 2016 Jan;170A(1):162-9. Epub 2015 Sep 3 doi: 10.1002/ajmg.a.37346. PMID: 26333654

Diagnosis

Aubert Mucca M, Patat O, Whalen S, Arnaud L, Barcia G, Buratti J, Cogné B, Doummar D, Karsenty C, Kenis S, Leguern E, Lesca G, Nava C, Nizon M, Piton A, Valence S, Villard L, Weckhuysen S, Keren B, Mignot C
J Med Genet 2022 May;59(5):505-510. Epub 2021 Apr 2 doi: 10.1136/jmedgenet-2020-107511. PMID: 33811134
Wang H, Zhang X, Ding H
Clin Dysmorphol 2021 Jan;30(1):27-31. doi: 10.1097/MCD.0000000000000345. PMID: 32956079
Hara-Isono K, Matsubara K, Fuke T, Yamazawa K, Satou K, Murakami N, Saitoh S, Nakabayashi K, Hata K, Ogata T, Fukami M, Kagami M
Clin Epigenetics 2020 Oct 22;12(1):159. doi: 10.1186/s13148-020-00949-8. PMID: 33092629Free PMC Article
Hamilton MJ, Suri M
Adv Genet 2020;105:137-174. Epub 2020 May 26 doi: 10.1016/bs.adgen.2020.03.002. PMID: 32560786
Mastrangelo M, Scheffer IE, Bramswig NC, Nair LD, Myers CT, Dentici ML, Korenke GC, Schoch K, Campeau PM, White SM, Shashi V, Kansagra S, Van Essen AJ, Leuzzi V
Epileptic Disord 2016 Jun 1;18(2):123-36. doi: 10.1684/epd.2016.0830. PMID: 27267311

Therapy

Mastrangelo M, Scheffer IE, Bramswig NC, Nair LD, Myers CT, Dentici ML, Korenke GC, Schoch K, Campeau PM, White SM, Shashi V, Kansagra S, Van Essen AJ, Leuzzi V
Epileptic Disord 2016 Jun 1;18(2):123-36. doi: 10.1684/epd.2016.0830. PMID: 27267311

Prognosis

Tian MQ, Li RK, Yang F, Shu XM, Li J, Chen J, Peng LY, Yu XH, Yang CJ
CNS Neurosci Ther 2023 Jan;29(1):270-281. Epub 2022 Oct 25 doi: 10.1111/cns.14001. PMID: 36285361Free PMC Article
Kagami M, Hara-Isono K, Matsubara K, Nakabayashi K, Narumi S, Fukami M, Ohkubo Y, Saitsu H, Takada S, Ogata T
Clin Epigenetics 2021 May 26;13(1):119. doi: 10.1186/s13148-021-01106-5. PMID: 34039421Free PMC Article
Mégarbané A, Al-Ali R, Choucair N, Lek M, Wang E, Ladjimi M, Rose CM, Hobeika R, Macary Y, Temanni R, Jithesh PV, Chouchane A, Sastry KS, Thomas R, Tomei S, Liu W, Marincola FM, MacArthur D, Chouchane L
BMC Med Genet 2016 Jun 10;17(1):42. doi: 10.1186/s12881-016-0304-4. PMID: 27282200Free PMC Article

Clinical prediction guides

Napoli G, Panzironi N, Traversa A, Catalanotto C, Pace V, Petrizzelli F, Giovannetti A, Lazzari S, Cogoni C, Tartaglia M, Carella M, Mazza T, Pizzuti A, Parisi C, Caputo V
Mol Neurobiol 2022 Aug;59(8):4825-4838. Epub 2022 May 31 doi: 10.1007/s12035-022-02886-4. PMID: 35639255Free PMC Article
Kagami M, Hara-Isono K, Matsubara K, Nakabayashi K, Narumi S, Fukami M, Ohkubo Y, Saitsu H, Takada S, Ogata T
Clin Epigenetics 2021 May 26;13(1):119. doi: 10.1186/s13148-021-01106-5. PMID: 34039421Free PMC Article
Mégarbané A, Al-Ali R, Choucair N, Lek M, Wang E, Ladjimi M, Rose CM, Hobeika R, Macary Y, Temanni R, Jithesh PV, Chouchane A, Sastry KS, Thomas R, Tomei S, Liu W, Marincola FM, MacArthur D, Chouchane L
BMC Med Genet 2016 Jun 10;17(1):42. doi: 10.1186/s12881-016-0304-4. PMID: 27282200Free PMC Article
Mastrangelo M, Scheffer IE, Bramswig NC, Nair LD, Myers CT, Dentici ML, Korenke GC, Schoch K, Campeau PM, White SM, Shashi V, Kansagra S, Van Essen AJ, Leuzzi V
Epileptic Disord 2016 Jun 1;18(2):123-36. doi: 10.1684/epd.2016.0830. PMID: 27267311
Shen JJ
Clin Dysmorphol 2015 Apr;24(2):55-60. doi: 10.1097/MCD.0000000000000072. PMID: 25629734Free PMC Article

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