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X-linked parkinsonism-spasticity syndrome(XPDS)

MedGen UID:
813052
•Concept ID:
C3806722
•
Disease or Syndrome
Synonym: Parkinsonism with spasticity, X-linked
SNOMED CT: X-linked parkinsonism with spasticity syndrome (770757004); XPDS - X-linked parkinsonism with spasticity syndrome (770757004)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
•Concept ID:
C1845977
•
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
See: This record
X-linked recessive inheritance (Orphanet)
 
Gene (location): ATP6AP2 (Xp11.4)
 
Monarch Initiative: MONDO:0010482
OMIM®: 300911
Orphanet: ORPHA363654

Definition

A rare genetic neurological disorder with characteristics of parkinsonian features (including resting or action tremor, cogwheel rigidity, hypomimia and bradykinesia) associated with variably penetrant spasticity, hyperactive deep tendon reflexes and Babinski sign. There is evidence this disease is caused by hemizygous mutation in the ATP6AP2 gene on chromosome Xp11. [from SNOMEDCT_US]

Clinical features

From HPO
Spasticity
MedGen UID:
7753
•Concept ID:
C0026838
•
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
See: Feature record | Search on this feature
Babinski sign
MedGen UID:
19708
•Concept ID:
C0034935
•
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
See: Feature record | Search on this feature
Hyperreflexia
MedGen UID:
57738
•Concept ID:
C0151889
•
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
See: Feature record | Search on this feature
Bradykinesia
MedGen UID:
115925
•Concept ID:
C0233565
•
Sign or Symptom
Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).
See: Feature record | Search on this feature
Resting tremor
MedGen UID:
66697
•Concept ID:
C0234379
•
Sign or Symptom
A resting tremor occurs when muscles are at rest and becomes less noticeable or disappears when the affected muscles are moved. Resting tremors are often slow and coarse.
See: Feature record | Search on this feature
Parkinsonian disorder
MedGen UID:
66079
•Concept ID:
C0242422
•
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
See: Feature record | Search on this feature
Cogwheel rigidity
MedGen UID:
57469
•Concept ID:
C0151564
•
Sign or Symptom
A type of rigidity in which a muscle responds with cogwheellike jerks to the use of constant force in bending the limb (i.e., it gives way in little, repeated jerks when the muscle is passively stretched).
See: Feature record | Search on this feature
Hypomimic face
MedGen UID:
208827
•Concept ID:
C0813217
•
Finding
A reduced degree of motion of the muscles beneath the skin of the face, often associated with reduced facial crease formation.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVX-linked parkinsonism-spasticity syndrome
Follow this link to review classifications for X-linked parkinsonism-spasticity syndrome in Orphanet.

Professional guidelines

PubMed

VEXAS syndrome: Clinical manifestations, diagnosis, and treatment.
Loeza-Uribe MP, Hinojosa-Azaola A, Sánchez-Hernández BE, Crispín JC, Apodaca-Chávez E, Ferrada MA, Martín-Nares E
Reumatol Clin (Engl Ed) 2024 Jan;20(1):47-56. Epub 2023 Dec 29 doi: 10.1016/j.reumae.2023.12.004. PMID: 38160120
Alport Syndrome: Achieving Early Diagnosis and Treatment.
Kashtan CE
Am J Kidney Dis 2021 Feb;77(2):272-279. Epub 2020 Jul 22 doi: 10.1053/j.ajkd.2020.03.026. PMID: 32712016
Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations.
Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, Thompson CJ
Am J Med 2013 Oct;126(10 Suppl 1):S1-42. doi: 10.1016/j.amjmed.2013.07.006. PMID: 24074529

Recent clinical studies

Etiology

X-Linked Epilepsies: A Narrative Review.
Bernardo P, Cuccurullo C, Rubino M, De Vita G, Terrone G, Bilo L, Coppola A
Int J Mol Sci 2024 Apr 8;25(7) doi: 10.3390/ijms25074110. PMID: 38612920Free PMC Article
Epigenetic Causes of Overgrowth Syndromes.
Lui JC, Baron J
J Clin Endocrinol Metab 2024 Jan 18;109(2):312-320. doi: 10.1210/clinem/dgad420. PMID: 37450557Free PMC Article
Molecular diagnosis based on comprehensive genetic testing in 800 Chinese families with non-syndromic inherited retinal dystrophies.
Liu X, Tao T, Zhao L, Li G, Yang L
Clin Exp Ophthalmol 2021 Jan;49(1):46-59. Epub 2020 Nov 2 doi: 10.1111/ceo.13875. PMID: 33090715
Inherited ichthyosis: Non-syndromic forms.
Takeichi T, Akiyama M
J Dermatol 2016 Mar;43(3):242-51. doi: 10.1111/1346-8138.13243. PMID: 26945532
Amelogenesis imperfecta.
Crawford PJ, Aldred M, Bloch-Zupan A
Orphanet J Rare Dis 2007 Apr 4;2:17. doi: 10.1186/1750-1172-2-17. PMID: 17408482Free PMC Article

Diagnosis

X-Linked Epilepsies: A Narrative Review.
Bernardo P, Cuccurullo C, Rubino M, De Vita G, Terrone G, Bilo L, Coppola A
Int J Mol Sci 2024 Apr 8;25(7) doi: 10.3390/ijms25074110. PMID: 38612920Free PMC Article
VEXAS syndrome: An update.
Khitri MY, Hadjadj J, Mekinian A, Jachiet V
Joint Bone Spine 2024 Jul;91(4):105700. Epub 2024 Feb 1 doi: 10.1016/j.jbspin.2024.105700. PMID: 38307404
VEXAS Syndrome-A Review of Pathophysiology, Presentation, and Prognosis.
Koster MJ, Samec MJ, Warrington KJ
J Clin Rheumatol 2023 Sep 1;29(6):298-306. Epub 2022 Oct 17 doi: 10.1097/RHU.0000000000001905. PMID: 36251488
The X-linked retinopathies: Physiological insights, pathogenic mechanisms, phenotypic features and novel therapies.
De Silva SR, Arno G, Robson AG, Fakin A, Pontikos N, Mohamed MD, Bird AC, Moore AT, Michaelides M, Webster AR, Mahroo OA
Prog Retin Eye Res 2021 May;82:100898. Epub 2020 Aug 26 doi: 10.1016/j.preteyeres.2020.100898. PMID: 32860923
Inherited ichthyosis: Non-syndromic forms.
Takeichi T, Akiyama M
J Dermatol 2016 Mar;43(3):242-51. doi: 10.1111/1346-8138.13243. PMID: 26945532

Therapy

VEXAS Syndrome-A Review of Pathophysiology, Presentation, and Prognosis.
Koster MJ, Samec MJ, Warrington KJ
J Clin Rheumatol 2023 Sep 1;29(6):298-306. Epub 2022 Oct 17 doi: 10.1097/RHU.0000000000001905. PMID: 36251488
X-chromosome inactivation: implications in human disease.
Pereira G, Dória S
J Genet 2021;100 PMID: 34553695
Alport Syndrome: Achieving Early Diagnosis and Treatment.
Kashtan CE
Am J Kidney Dis 2021 Feb;77(2):272-279. Epub 2020 Jul 22 doi: 10.1053/j.ajkd.2020.03.026. PMID: 32712016
Hypophosphatemic Rickets.
Bitzan M, Goodyer PR
Pediatr Clin North Am 2019 Feb;66(1):179-207. doi: 10.1016/j.pcl.2018.09.004. PMID: 30454743
Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations.
Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, Thompson CJ
Am J Med 2013 Oct;126(10 Suppl 1):S1-42. doi: 10.1016/j.amjmed.2013.07.006. PMID: 24074529

Prognosis

Alport Syndrome.
Chavez E, Goncalves S, Rheault MN, Fornoni A
Adv Kidney Dis Health 2024 May;31(3):170-179. doi: 10.1053/j.akdh.2024.02.004. PMID: 39004457
VEXAS Syndrome-A Review of Pathophysiology, Presentation, and Prognosis.
Koster MJ, Samec MJ, Warrington KJ
J Clin Rheumatol 2023 Sep 1;29(6):298-306. Epub 2022 Oct 17 doi: 10.1097/RHU.0000000000001905. PMID: 36251488
IPEX Syndrome: Genetics and Treatment Options.
Ben-Skowronek I
Genes (Basel) 2021 Feb 24;12(3) doi: 10.3390/genes12030323. PMID: 33668198Free PMC Article
Retinitis pigmentosa.
Hamel C
Orphanet J Rare Dis 2006 Oct 11;1:40. doi: 10.1186/1750-1172-1-40. PMID: 17032466Free PMC Article
Emery-Dreifuss syndrome.
Emery AE
J Med Genet 1989 Oct;26(10):637-41. doi: 10.1136/jmg.26.10.637. PMID: 2685312Free PMC Article

Clinical prediction guides

Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS.
Ferrada MA, Sikora KA, Luo Y, Wells KV, Patel B, Groarke EM, Ospina Cardona D, Rominger E, Hoffmann P, Le MT, Deng Z, Quinn KA, Rose E, Tsai WL, Wigerblad G, Goodspeed W, Jones A, Wilson L, Schnappauf O, Laird RS, Kim J, Allen C, Sirajuddin A, Chen M, Gadina M, Calvo KR, Kaplan MJ, Colbert RA, Aksentijevich I, Young NS, Savic S, Kastner DL, Ombrello AK, Beck DB, Grayson PC
Arthritis Rheumatol 2021 Oct;73(10):1886-1895. Epub 2021 Aug 31 doi: 10.1002/art.41743. PMID: 33779074
HUWE1 variants cause dominant X-linked intellectual disability: a clinical study of 21 patients.
Moortgat S, Berland S, Aukrust I, Maystadt I, Baker L, Benoit V, Caro-Llopis A, Cooper NS, Debray FG, Faivre L, Gardeitchik T, Haukanes BI, Houge G, Kivuva E, Martinez F, Mehta SG, Nassogne MC, Powell-Hamilton N, Pfundt R, Rosello M, Prescott T, Vasudevan P, van Loon B, Verellen-Dumoulin C, Verloes A, Lippe CV, Wakeling E, Wilkie AOM, Wilson L, Yuen A, Study D, Low KJ, Newbury-Ecob RA
Eur J Hum Genet 2018 Jan;26(1):64-74. Epub 2017 Nov 27 doi: 10.1038/s41431-017-0038-6. PMID: 29180823Free PMC Article
Amelogenesis imperfecta.
Crawford PJ, Aldred M, Bloch-Zupan A
Orphanet J Rare Dis 2007 Apr 4;2:17. doi: 10.1186/1750-1172-2-17. PMID: 17408482Free PMC Article
Aicardi syndrome.
Rosser T
Arch Neurol 2003 Oct;60(10):1471-3. doi: 10.1001/archneur.60.10.1471. PMID: 14568821
X-linked scapuloperoneal syndrome.
Thomas PK, Calne DB, Elliott CF
J Neurol Neurosurg Psychiatry 1972 Apr;35(2):208-15. doi: 10.1136/jnnp.35.2.208. PMID: 4113956Free PMC Article

Recent systematic reviews

How to treat VEXAS syndrome: a systematic review on effectiveness and safety of current treatment strategies.
Boyadzhieva Z, Ruffer N, Kötter I, Krusche M
Rheumatology (Oxford) 2023 Nov 2;62(11):3518-3525. doi: 10.1093/rheumatology/kead240. PMID: 37233149
ATR-X syndrome: genetics, clinical spectrum, and management.
León NY, Harley VR
Hum Genet 2021 Dec;140(12):1625-1634. Epub 2021 Sep 15 doi: 10.1007/s00439-021-02361-5. PMID: 34524523
Oral Manifestations of Rett Syndrome-A Systematic Review.
Mahdi SS, Jafri HA, Allana R, Amenta F, Khawaja M, Qasim SSB
Int J Environ Res Public Health 2021 Jan 28;18(3) doi: 10.3390/ijerph18031162. PMID: 33525609Free PMC Article
A systematic review and evidence-based guideline for diagnosis and treatment of Menkes disease.
Vairo FPE, Chwal BC, Perini S, Ferreira MAP, de Freitas Lopes AC, Saute JAM
Mol Genet Metab 2019 Jan;126(1):6-13. Epub 2018 Dec 11 doi: 10.1016/j.ymgme.2018.12.005. PMID: 30594472
X linked mental retardation.
Rejeb I, Ben Jemaa L, Chaabouni H
Tunis Med 2009 May;87(5):311-8. PMID: 19927760

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