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Supranuclear gaze palsy

MedGen UID:
314030
Concept ID:
C1720037
Disease or Syndrome; Finding
Synonym: Supranuclear gaze paralysis
SNOMED CT: Supranuclear gaze palsy (420675003)
 
HPO: HP:0000605

Definition

A supranuclear gaze palsy is an inability to look in a particular direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal. [from HPO]

Conditions with this feature

Inherited Creutzfeldt-Jakob disease
MedGen UID:
155837
Concept ID:
C0751254
Disease or Syndrome
Genetic prion disease generally manifests with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. The three major phenotypes of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Although these phenotypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset typically ranges from 50 to 60 years. The disease course ranges from a few months in gCJD and FFI to a few (up to 4, and in rare cases up to 10) years in GSS syndrome.
Supranuclear palsy, progressive, 2
MedGen UID:
324446
Concept ID:
C1836148
Disease or Syndrome
Kufor-Rakeb syndrome
MedGen UID:
338281
Concept ID:
C1847640
Disease or Syndrome
Kufor-Rakeb syndrome is a rare autosomal recessive form of juvenile-onset atypical Parkinson disease (PARK9) associated with supranuclear gaze palsy, spasticity, and dementia. Some patients have neuroradiologic evidence of iron deposition in the basal ganglia, indicating that the pathogenesis of PARK9 can be considered among the syndromes of neurodegeneration with brain iron accumulation (NBIA; see 234200) (summary by Bruggemann et al., 2010). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease (PD), see 168600. Biallelic mutation in the ATP13A2 gene also causes autosomal recessive spastic paraplegia-78 (SPG78; 617225), an adult-onset neurodegenerative disorder with overlapping features. Patients with SPG78 have later onset and prominent spasticity, but rarely parkinsonism. Loss of ATP13A2 function results in a multidimensional spectrum of neurologic features reflecting various regions of the brain and nervous system, including cortical, pyramidal, extrapyramidal, brainstem, cerebellar, and peripheral (summary by Estrada-Cuzcano et al., 2017).
Spinocerebellar ataxia type 34
MedGen UID:
338703
Concept ID:
C1851481
Disease or Syndrome
Spinocerebellar ataxia-34 (SCA34) is an autosomal dominant disorder characterized by slowly progressive cerebellar ataxia. Onset usually occurs during the young adult years, and most patients remain ambulatory until late in life. One family with SCA34 also had onset of erythema and hyperkeratosis in early childhood (Cadieux-Dion et al., 2014), whereas other families have additional neurologic signs, including ocular movement disturbances and pyramidal tract signs (Ozaki et al., 2015). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Gaucher disease due to saposin C deficiency
MedGen UID:
350479
Concept ID:
C1864651
Disease or Syndrome
Any Gaucher disease in which the cause of the disease is a mutation in the PSAP gene.
Spastic ataxia 1
MedGen UID:
409988
Concept ID:
C1970107
Disease or Syndrome
Hereditary spastic ataxia comprises a heterogeneous group of progressive neurodegenerative disorders characterized by lower-limb spasticity and generalized ataxia with dysarthria, impaired ocular movements, and gait disturbance. Spastic ataxia-1 (SPAX1) is an autosomal dominant form of the disorder with onset between the ages of 10 and 20 years. Other clinical features are supranuclear gaze palsy, hyperreflexia, hypertonicity, dystonia, pes cavus, mild ptosis, and decreased vibration sense in the lower limbs. Symptom severity is variable, but neither life span nor cognition is affected (summary by Meijer et al., 2002 and Bourassa et al., 2012). Genetic Heterogeneity of Spastic Ataxia See also SPAX2 (611302), caused by mutation in the KIF1C gene (603060) on chromosome 17p13; SPAX3 (611390), caused by rearrangements of the MARS2 gene (609728) on chromosome 2q33; SPAX4 (613672), caused by mutation in the MTPAP gene (613669) on chromosome 10p11; SPAX5 (614487), caused by mutation in the AFG3L2 gene (604581) on chromosome 18p11; SPAX6 (270550), caused by mutation in the SACS gene (604490) on chromosome 13q12; SPAX7 (108650); SPAX8 (617560), caused by mutation in the NKX6-2 gene (605955) on chromosome 8q21; SPAX9 (618438), caused by mutation in the CHP1 gene (606988) on chromosome 15q15; and SPAX10 (620666), caused by mutation in the COQ4 gene (612898) on chromosome 9q34.
Early-onset Parkinson disease 20
MedGen UID:
816154
Concept ID:
C3809824
Disease or Syndrome
Parkinson disease-20 is an autosomal recessive neurodegenerative disorder characterized by young adult-onset of parkinsonism. Additional features may include seizures, cognitive decline, abnormal eye movements, and dystonia (summary by Krebs et al., 2013 and Quadri et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see PD (168600).
Cerebral palsy, spastic quadriplegic, 3
MedGen UID:
934734
Concept ID:
C4310767
Disease or Syndrome
Any spastic quadriplegia in which the cause of the disease is a mutation in the ADD3 gene.
Supranuclear palsy, progressive, 1
MedGen UID:
1640811
Concept ID:
C4551863
Disease or Syndrome
The spectrum of clinical manifestations of MAPT-related frontotemporal dementia (MAPT-FTD) has expanded from its original description of frontotemporal dementia and parkinsonian manifestations to include changes in behavior, motor function, memory, and/or language. A recent retrospective study suggested that the majority of affected individuals have either behavioral changes consistent with a diagnosis of behavioral variant FTD (bvFTD) or, less commonly, a parkinsonian syndrome (i.e., progressive supranuclear palsy, corticobasal syndrome, or Parkinson disease). Fewer than 5% of people with MAPT-FTD have primary progressive aphasia or Alzheimer disease. Clinical presentation may differ between and within families with the same MAPT variant. MAPT-FTD is a progressive disorder that commonly ends with a relatively global dementia in which some affected individuals become mute. Progression of motor impairment in affected individuals results in some becoming chairbound and others bedbound. Mean disease duration is 9.3 (SD: 6.4) years but is individually variable and can be more than 30 years in some instances.
Spastic paraplegia 80, autosomal dominant
MedGen UID:
1682111
Concept ID:
C5193084
Disease or Syndrome
Spastic paraplegia-80 (SPG80) is an autosomal dominant juvenile-onset neurologic disorder characterized by onset of progressive spasticity and hyperreflexia affecting mainly the lower limbs and resulting in difficulty walking or loss of independent ambulation, sometimes as early as the second decade. Some patients may have cerebellar signs and mild cognitive impairment, but most have a pure form of the disorder (summary by Farazi Fard et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).
Autosomal recessive spastic paraplegia type 78
MedGen UID:
1799316
Concept ID:
C5567893
Disease or Syndrome
Autosomal recessive spastic paraplegia-78 is an adult-onset neurodegenerative disorder characterized predominantly by spasticity and muscle weakness of the lower limbs, resulting in gait difficulties and loss of ambulation in some patients. Affected individuals also have cerebellar signs, such as dysarthria, oculomotor disturbances, and limb and gait ataxia; brain imaging shows cerebellar atrophy. Some patients may have mild cognitive impairment or frank dementia. The phenotype is highly variable (summary by Estrada-Cuzcano et al., 2017). Biallelic mutation in the ATP13A2 gene also causes Kufor-Rakeb syndrome (KRS; 606693), a neurodegenerative disorder with overlapping features. Patients with KRS have earlier onset and prominent parkinsonism. Loss of ATP13A2 function results in a multidimensional spectrum of neurologic features reflecting various regions of the brain and nervous system, including cortical, pyramidal, extrapyramidal, brainstem, cerebellar, and peripheral (summary by Estrada-Cuzcano et al., 2017).
Frontotemporal dementia and/or amyotrophic lateral sclerosis 1
MedGen UID:
1830423
Concept ID:
C5779877
Disease or Syndrome
C9orf72 frontotemporal dementia and/or amyotrophic lateral sclerosis (C9orf72-FTD/ALS) is characterized most often by frontotemporal dementia (FTD) and upper and lower motor neuron disease (MND); however, atypical presentations also occur. Age at onset is usually between 50 and 64 years (range: 20-91 years) irrespective of the presenting manifestations, which may be pure FTD, pure amyotrophic lateral sclerosis (ALS), or a combination of the two phenotypes. The clinical presentation is highly heterogeneous and may differ between and within families, causing an unpredictable pattern and age of onset of clinical manifestations. The presence of MND correlates with an earlier age of onset and a worse overall prognosis.

Professional guidelines

PubMed

Wittke C, Petkovic S, Dobricic V, Schaake S; MDS‐endorsed PSP Study Group, Respondek G, Weissbach A, Madoev H, Trinh J, Vollstedt EJ, Kuhnke N, Lohmann K, Dulovic Mahlow M, Marras C, König IR, Stamelou M, Bonifati V, Lill CM, Kasten M, Huppertz HJ, Höglinger G, Klein C
Mov Disord 2021 Jul;36(7):1499-1510. Epub 2021 Mar 19 doi: 10.1002/mds.28517. PMID: 34396589Free PMC Article
Berry-Kravis E
Semin Pediatr Neurol 2021 Apr;37:100879. Epub 2021 Feb 12 doi: 10.1016/j.spen.2021.100879. PMID: 33892845
Patterson MC, Hendriksz CJ, Walterfang M, Sedel F, Vanier MT, Wijburg F; NP-C Guidelines Working Group
Mol Genet Metab 2012 Jul;106(3):330-44. Epub 2012 May 8 doi: 10.1016/j.ymgme.2012.03.012. PMID: 22572546

Recent clinical studies

Etiology

Macher S, Milenkovic I, Zrzavy T, Höftberger R, Seidel S, Berger-Sieczkowski E, Berger T, Rommer PS, Wiest G
Front Immunol 2021;12:753856. Epub 2021 Sep 30 doi: 10.3389/fimmu.2021.753856. PMID: 34659261Free PMC Article
Wen Y, Zhou Y, Jiao B, Shen L
J Parkinsons Dis 2021;11(1):93-105. doi: 10.3233/JPD-202302. PMID: 33104043Free PMC Article
Weissbach A, Wittke C, Kasten M, Klein C
Int Rev Neurobiol 2019;149:207-235. Epub 2019 Nov 25 doi: 10.1016/bs.irn.2019.10.011. PMID: 31779813
Ali F, Josephs K
Expert Rev Neurother 2018 Jul;18(7):603-616. Epub 2018 Jun 28 doi: 10.1080/14737175.2018.1489241. PMID: 29902389
Vanier MT
Handb Clin Neurol 2013;113:1717-21. doi: 10.1016/B978-0-444-59565-2.00041-1. PMID: 23622394

Diagnosis

Ali F, Josephs K
Expert Rev Neurother 2018 Jul;18(7):603-616. Epub 2018 Jun 28 doi: 10.1080/14737175.2018.1489241. PMID: 29902389
Armstrong MJ
Curr Neurol Neurosci Rep 2018 Feb 17;18(3):12. doi: 10.1007/s11910-018-0819-5. PMID: 29455271
Vanier MT
Handb Clin Neurol 2013;113:1717-21. doi: 10.1016/B978-0-444-59565-2.00041-1. PMID: 23622394
Clark D, Eggenberger E
Curr Opin Ophthalmol 2012 Nov;23(6):491-6. doi: 10.1097/ICU.0b013e328358ba14. PMID: 23014265
Vanier MT
Orphanet J Rare Dis 2010 Jun 3;5:16. doi: 10.1186/1750-1172-5-16. PMID: 20525256Free PMC Article

Therapy

Stamelou M, Höglinger G
CNS Drugs 2016 Jul;30(7):629-36. doi: 10.1007/s40263-016-0347-2. PMID: 27222018
Eggers SD, Horn AK, Roeber S, Härtig W, Nair G, Reich DS, Leigh RJ
Ann N Y Acad Sci 2015 Apr;1343(1):113-9. Epub 2015 Feb 26 doi: 10.1111/nyas.12666. PMID: 25721480Free PMC Article
Vanier MT
Orphanet J Rare Dis 2010 Jun 3;5:16. doi: 10.1186/1750-1172-5-16. PMID: 20525256Free PMC Article
Warren NM, Piggott MA, Perry EK, Burn DJ
Brain 2005 Feb;128(Pt 2):239-49. Epub 2005 Jan 13 doi: 10.1093/brain/awh391. PMID: 15649952
Louis ED
Curr Neurol Neurosci Rep 2003 Nov;3(6):470-5. doi: 10.1007/s11910-003-0049-2. PMID: 14565900

Prognosis

Ali F, Josephs K
Expert Rev Neurother 2018 Jul;18(7):603-616. Epub 2018 Jun 28 doi: 10.1080/14737175.2018.1489241. PMID: 29902389
Arena JE, Weigand SD, Whitwell JL, Hassan A, Eggers SD, Höglinger GU, Litvan I, Josephs KA
J Neurol 2016 Feb;263(2):380-389. Epub 2015 Dec 24 doi: 10.1007/s00415-015-7990-2. PMID: 26705121
Clark D, Eggenberger E
Curr Opin Ophthalmol 2012 Nov;23(6):491-6. doi: 10.1097/ICU.0b013e328358ba14. PMID: 23014265
Vanier MT
Orphanet J Rare Dis 2010 Jun 3;5:16. doi: 10.1186/1750-1172-5-16. PMID: 20525256Free PMC Article
Mitra K, Gangopadhaya PK, Das SK
Neurol India 2003 Jun;51(2):183-8. PMID: 14570999

Clinical prediction guides

Bolton SC, Soran V, Marfa MP, Imrie J, Gissen P, Jahnova H, Sharma R, Jones S, Santra S, Crushell E, Stampfer M, Coll MJ, Dawson C, Mathieson T, Green J, Dardis A, Bembi B, Patterson MC, Vanier MT, Geberhiwot T
Orphanet J Rare Dis 2022 Feb 14;17(1):51. doi: 10.1186/s13023-022-02200-4. PMID: 35164809Free PMC Article
Ali F, Josephs K
Expert Rev Neurother 2018 Jul;18(7):603-616. Epub 2018 Jun 28 doi: 10.1080/14737175.2018.1489241. PMID: 29902389
Martin WRW, Hartlein J, Racette BA, Cairns N, Perlmutter JS
Parkinsonism Relat Disord 2017 May;38:68-71. Epub 2017 Feb 24 doi: 10.1016/j.parkreldis.2017.02.027. PMID: 28256434Free PMC Article
Arena JE, Weigand SD, Whitwell JL, Hassan A, Eggers SD, Höglinger GU, Litvan I, Josephs KA
J Neurol 2016 Feb;263(2):380-389. Epub 2015 Dec 24 doi: 10.1007/s00415-015-7990-2. PMID: 26705121
Vanier MT
Orphanet J Rare Dis 2010 Jun 3;5:16. doi: 10.1186/1750-1172-5-16. PMID: 20525256Free PMC Article

Recent systematic reviews

Wittke C, Petkovic S, Dobricic V, Schaake S; MDS‐endorsed PSP Study Group, Respondek G, Weissbach A, Madoev H, Trinh J, Vollstedt EJ, Kuhnke N, Lohmann K, Dulovic Mahlow M, Marras C, König IR, Stamelou M, Bonifati V, Lill CM, Kasten M, Huppertz HJ, Höglinger G, Klein C
Mov Disord 2021 Jul;36(7):1499-1510. Epub 2021 Mar 19 doi: 10.1002/mds.28517. PMID: 34396589Free PMC Article
Parthimos TP, Schulpis KH
Clin Gerontol 2020 Mar-Apr;43(2):155-180. Epub 2019 Nov 22 doi: 10.1080/07317115.2019.1694115. PMID: 31752626
Lopez G, Bayulkem K, Hallett M
Acta Neurol Scand 2016 Oct;134(4):242-9. Epub 2016 Jan 6 doi: 10.1111/ane.12546. PMID: 27070344Free PMC Article
Wilke C, Pomper JK, Biskup S, Puskás C, Berg D, Synofzik M
J Neurol 2016 Mar;263(3):558-74. Epub 2016 Jan 25 doi: 10.1007/s00415-016-8021-7. PMID: 26810719
Walterfang M, Chien YH, Imrie J, Rushton D, Schubiger D, Patterson MC
Orphanet J Rare Dis 2012 Oct 6;7:76. doi: 10.1186/1750-1172-7-76. PMID: 23039766Free PMC Article

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