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Joubert syndrome 28(JBTS28)

MedGen UID:
934672
Concept ID:
C4310705
Disease or Syndrome
Synonym: JBTS28
 
Gene (location): MKS1 (17q22)
 
Monarch Initiative: MONDO:0014928
OMIM®: 617121

Disease characteristics

Excerpted from the GeneReview: Joubert Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen. [from GeneReviews]
Authors:
Melissa Parisi  |  Ian Glass   view full author information

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
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.
Lower limb hyperreflexia
MedGen UID:
322973
Concept ID:
C1836696
Finding
Molar tooth sign on MRI
MedGen UID:
400670
Concept ID:
C1865060
Finding
An abnormal appearance of the midbrain in axial magnetic resonance imaging in which the elongated superior cerebellar peduncles give the midbrain an appearance reminiscent of a molar or wisdom tooth.
Oculomotor apraxia
MedGen UID:
483686
Concept ID:
C3489733
Disease or Syndrome
Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancelation of the vestibulo-ocular reflex.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Broad forehead
MedGen UID:
338610
Concept ID:
C1849089
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
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.
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).
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
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.
Optic disc pallor
MedGen UID:
108218
Concept ID:
C0554970
Finding
A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression.
Pigmentary retinopathy
MedGen UID:
1643295
Concept ID:
C4551715
Disease or Syndrome
An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss.

Professional guidelines

PubMed

Krajden Haratz K, Oliveira Szejnfeld P, Govindaswamy M, Leibovitz Z, Gindes L, Severino M, Rossi A, Paladini D, Garcia Rodriguez R, Ben-Sira L, Borkowski Tillman T, Gupta R, Lotem G, Raz N, Hamamoto TENK, Kidron D, Arad A, Birnbaum R, Brussilov M, Pomar L, Vial Y, Leventer RJ, McGillivray G, Fink M, Krzeszowski W, Fernandes Moron A, Lev D, Tamarkin M, Shalev J, Har Toov J, Lerman-Sagie T, Malinger G
Ultrasound Obstet Gynecol 2021 Dec;58(6):864-874. doi: 10.1002/uog.23660. PMID: 33942916
Brooks BP, Zein WM, Thompson AH, Mokhtarzadeh M, Doherty DA, Parisi M, Glass IA, Malicdan MC, Vilboux T, Vemulapalli M, Mullikin JC, Gahl WA, Gunay-Aygun M
Ophthalmology 2018 Dec;125(12):1937-1952. Epub 2018 Jul 25 doi: 10.1016/j.ophtha.2018.05.026. PMID: 30055837Free PMC Article
Yamasaki M, Nonaka M, Bamba Y, Teramoto C, Ban C, Pooh RK
Semin Fetal Neonatal Med 2012 Dec;17(6):330-5. Epub 2012 Oct 23 doi: 10.1016/j.siny.2012.07.004. PMID: 23089488

Recent clinical studies

Etiology

Simonini C, Floeck A, Strizek B, Mueller A, Gembruch U, Geipel A
Arch Gynecol Obstet 2022 Jul;306(1):71-83. Epub 2021 Oct 1 doi: 10.1007/s00404-021-06265-7. PMID: 34596737Free PMC Article
Cotes C, Bonfante E, Lazor J, Jadhav S, Caldas M, Swischuk L, Riascos R
Neuroradiol J 2015 Jun;28(3):238-53. doi: 10.1177/1971400915576665. PMID: 26246090Free PMC Article
Bachmann-Gagescu R, Phelps IG, Dempsey JC, Sharma VA, Ishak GE, Boyle EA, Wilson M, Marques Lourenço C, Arslan M; University of Washington Center for Mendelian Genomics, Shendure J, Doherty D
Hum Mutat 2015 Sep;36(9):831-5. Epub 2015 Jul 2 doi: 10.1002/humu.22821. PMID: 26096313Free PMC Article
Romani M, Mancini F, Micalizzi A, Poretti A, Miccinilli E, Accorsi P, Avola E, Bertini E, Borgatti R, Romaniello R, Ceylaner S, Coppola G, D'Arrigo S, Giordano L, Janecke AR, Lituania M, Ludwig K, Martorell L, Mazza T, Odent S, Pinelli L, Poo P, Santucci M, Signorini S, Simonati A, Spiegel R, Stanzial F, Steinlin M, Tabarki B, Wolf NI, Zibordi F, Boltshauser E, Valente EM
Hum Genet 2015 Jan;134(1):123-6. Epub 2014 Nov 19 doi: 10.1007/s00439-014-1508-3. PMID: 25407461Free PMC Article
Vogel TW, Dlouhy BJ, Menezes AH
Childs Nerv Syst 2012 Jul;28(7):1109-12. Epub 2012 Jan 10 doi: 10.1007/s00381-012-1682-3. PMID: 22231569

Diagnosis

Krajden Haratz K, Oliveira Szejnfeld P, Govindaswamy M, Leibovitz Z, Gindes L, Severino M, Rossi A, Paladini D, Garcia Rodriguez R, Ben-Sira L, Borkowski Tillman T, Gupta R, Lotem G, Raz N, Hamamoto TENK, Kidron D, Arad A, Birnbaum R, Brussilov M, Pomar L, Vial Y, Leventer RJ, McGillivray G, Fink M, Krzeszowski W, Fernandes Moron A, Lev D, Tamarkin M, Shalev J, Har Toov J, Lerman-Sagie T, Malinger G
Ultrasound Obstet Gynecol 2021 Dec;58(6):864-874. doi: 10.1002/uog.23660. PMID: 33942916
Phelps IG, Dempsey JC, Grout ME, Isabella CR, Tully HM, Doherty D, Bachmann-Gagescu R
Genet Med 2018 Feb;20(2):223-233. Epub 2017 Aug 3 doi: 10.1038/gim.2017.94. PMID: 28771248Free PMC Article
Bachmann-Gagescu R, Phelps IG, Dempsey JC, Sharma VA, Ishak GE, Boyle EA, Wilson M, Marques Lourenço C, Arslan M; University of Washington Center for Mendelian Genomics, Shendure J, Doherty D
Hum Mutat 2015 Sep;36(9):831-5. Epub 2015 Jul 2 doi: 10.1002/humu.22821. PMID: 26096313Free PMC Article
Bayram Y, Aydin H, Gambin T, Akdemir ZC, Atik MM, Karaca E, Karaman A, Pehlivan D, Jhangiani SN, Gibbs RA, Lupski JR
Am J Med Genet A 2015 Sep;167A(9):2132-7. Epub 2015 Apr 6 doi: 10.1002/ajmg.a.37092. PMID: 25846457Free PMC Article
Vogel TW, Dlouhy BJ, Menezes AH
Childs Nerv Syst 2012 Jul;28(7):1109-12. Epub 2012 Jan 10 doi: 10.1007/s00381-012-1682-3. PMID: 22231569

Therapy

Chen L, Uchida H, Komine R, Kodama T, Nakao T, Okada N, Yanagi Y, Shimizu S, Abbas S, Fukuda A, Sakamoto S, Kasahara M
Pediatr Transplant 2024 Feb;28(1):e14640. Epub 2023 Nov 15 doi: 10.1111/petr.14640. PMID: 37965976
Brooks BP, Zein WM, Thompson AH, Mokhtarzadeh M, Doherty DA, Parisi M, Glass IA, Malicdan MC, Vilboux T, Vemulapalli M, Mullikin JC, Gahl WA, Gunay-Aygun M
Ophthalmology 2018 Dec;125(12):1937-1952. Epub 2018 Jul 25 doi: 10.1016/j.ophtha.2018.05.026. PMID: 30055837Free PMC Article
Seo H, Kwon EJ, You YA, Park Y, Min BJ, Yoo K, Hwang HS, Kim JH, Kim YJ
BMC Med Genomics 2018 Jan 24;11(1):4. doi: 10.1186/s12920-018-0323-4. PMID: 29368655Free PMC Article
Saleem SN, Zaki MS
AJNR Am J Neuroradiol 2010 Mar;31(3):424-9. Epub 2009 Nov 26 doi: 10.3174/ajnr.A1867. PMID: 19942698Free PMC Article

Prognosis

Phelps IG, Dempsey JC, Grout ME, Isabella CR, Tully HM, Doherty D, Bachmann-Gagescu R
Genet Med 2018 Feb;20(2):223-233. Epub 2017 Aug 3 doi: 10.1038/gim.2017.94. PMID: 28771248Free PMC Article
Bayram Y, Aydin H, Gambin T, Akdemir ZC, Atik MM, Karaca E, Karaman A, Pehlivan D, Jhangiani SN, Gibbs RA, Lupski JR
Am J Med Genet A 2015 Sep;167A(9):2132-7. Epub 2015 Apr 6 doi: 10.1002/ajmg.a.37092. PMID: 25846457Free PMC Article
Romani M, Mancini F, Micalizzi A, Poretti A, Miccinilli E, Accorsi P, Avola E, Bertini E, Borgatti R, Romaniello R, Ceylaner S, Coppola G, D'Arrigo S, Giordano L, Janecke AR, Lituania M, Ludwig K, Martorell L, Mazza T, Odent S, Pinelli L, Poo P, Santucci M, Signorini S, Simonati A, Spiegel R, Stanzial F, Steinlin M, Tabarki B, Wolf NI, Zibordi F, Boltshauser E, Valente EM
Hum Genet 2015 Jan;134(1):123-6. Epub 2014 Nov 19 doi: 10.1007/s00439-014-1508-3. PMID: 25407461Free PMC Article
Yamasaki M, Nonaka M, Bamba Y, Teramoto C, Ban C, Pooh RK
Semin Fetal Neonatal Med 2012 Dec;17(6):330-5. Epub 2012 Oct 23 doi: 10.1016/j.siny.2012.07.004. PMID: 23089488
Steinlin M, Schmid M, Landau K, Boltshauser E
Neuropediatrics 1997 Aug;28(4):204-11. doi: 10.1055/s-2007-973701. PMID: 9309710

Clinical prediction guides

Simonini C, Floeck A, Strizek B, Mueller A, Gembruch U, Geipel A
Arch Gynecol Obstet 2022 Jul;306(1):71-83. Epub 2021 Oct 1 doi: 10.1007/s00404-021-06265-7. PMID: 34596737Free PMC Article
Krajden Haratz K, Oliveira Szejnfeld P, Govindaswamy M, Leibovitz Z, Gindes L, Severino M, Rossi A, Paladini D, Garcia Rodriguez R, Ben-Sira L, Borkowski Tillman T, Gupta R, Lotem G, Raz N, Hamamoto TENK, Kidron D, Arad A, Birnbaum R, Brussilov M, Pomar L, Vial Y, Leventer RJ, McGillivray G, Fink M, Krzeszowski W, Fernandes Moron A, Lev D, Tamarkin M, Shalev J, Har Toov J, Lerman-Sagie T, Malinger G
Ultrasound Obstet Gynecol 2021 Dec;58(6):864-874. doi: 10.1002/uog.23660. PMID: 33942916
Lamônica DA, Ribeiro CD, Richieri-Costa A, Giacheti CM
Codas 2016 Nov-Dec;28(6):823-827. doi: 10.1590/2317-1782/20162015184. PMID: 28001274
Bayram Y, Aydin H, Gambin T, Akdemir ZC, Atik MM, Karaca E, Karaman A, Pehlivan D, Jhangiani SN, Gibbs RA, Lupski JR
Am J Med Genet A 2015 Sep;167A(9):2132-7. Epub 2015 Apr 6 doi: 10.1002/ajmg.a.37092. PMID: 25846457Free PMC Article
Romani M, Mancini F, Micalizzi A, Poretti A, Miccinilli E, Accorsi P, Avola E, Bertini E, Borgatti R, Romaniello R, Ceylaner S, Coppola G, D'Arrigo S, Giordano L, Janecke AR, Lituania M, Ludwig K, Martorell L, Mazza T, Odent S, Pinelli L, Poo P, Santucci M, Signorini S, Simonati A, Spiegel R, Stanzial F, Steinlin M, Tabarki B, Wolf NI, Zibordi F, Boltshauser E, Valente EM
Hum Genet 2015 Jan;134(1):123-6. Epub 2014 Nov 19 doi: 10.1007/s00439-014-1508-3. PMID: 25407461Free PMC Article

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