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Arthrogryposis with renal dysfunction and cholestasis syndrome(ARCS)

MedGen UID:
1647210
•Concept ID:
C4551984
•
Disease or Syndrome
Synonyms: ARC syndrome; Arthrogryposis multiplex congenita, renal dysfunction, and cholestasis; Arthrogryposis-renal dysfunction-cholestasis syndrome
SNOMED CT: Arthrogryposis with renal dysfunction and cholestasis syndrome (720513002); ARC (arthrogryposis, renal dysfunction, cholestasis) syndrome (720513002)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Monarch Initiative: MONDO:0017123
OMIM®: 208085
OMIM® Phenotypic series: PS208085
Orphanet: ORPHA2697

Definition

Arthrogryposis, renal dysfunction, and cholestasis-1 (ARCS1) is characterized by congenital joint contractures, renal tubular dysfunction, cholestasis with low GGT (612346) activity, severe failure to thrive, ichthyosis, and a defect in platelet alpha-granule biogenesis. Most patients with ARC do not survive past the first year of life (Gissen et al., 2006; Smith et al., 2012). Another form of arthrogryposis, renal dysfunction, and cholestasis, ARCS2 (613404), is caused by mutation in the VIPAR gene on chromosome 14q24 (613401). [from OMIM]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Arthrogryposis with renal dysfunction and cholestasis syndrome

Professional guidelines

PubMed

Diagnostic algorithm for neonatal intrahepatic cholestasis integrating single-gene testing and next-generation sequencing in East Asia.
Hahn JW, Lee H, Shin M, Seong MW, Moon JS, Ko JS
J Gastroenterol Hepatol 2024 May;39(5):964-974. Epub 2024 Feb 7 doi: 10.1111/jgh.16505. PMID: 38323732

Recent clinical studies

Etiology

Overlapping Machinery in Lysosome-Related Organelle Trafficking: A Lesson from Rare Multisystem Disorders.
Banushi B, Simpson F
Cells 2022 Nov 21;11(22) doi: 10.3390/cells11223702. PMID: 36429129Free PMC Article
Novel missense mutation in VPS33B is associated with isolated low gamma-glutamyltransferase cholestasis: Attenuated, incomplete phenotype of arthrogryposis, renal dysfunction, and cholestasis syndrome.
Qiu YL, Liu T, Abuduxikuer K, Hao CZ, Gong JY, Zhang MH, Li LT, Yan YY, Li JQ, Wang JS
Hum Mutat 2019 Dec;40(12):2247-2257. Epub 2019 Sep 3 doi: 10.1002/humu.23770. PMID: 31479177
Novel VIPAS39 mutation in a syndromic patient with arthrogryposis, renal tubular dysfunction and intrahepatic cholestasis.
Aflatounian M, Smith H, Farahani F, Tofighi Naeem A, Straatman-Iwanowska A, Zoghi S, Khatri U, Tajdini P, Fallahi GH, Gissen P, Rezaei N
Eur J Med Genet 2016 Apr;59(4):237-9. Epub 2016 Jan 23 doi: 10.1016/j.ejmg.2016.01.005. PMID: 26808426
Orthopaedic manifestations of arthrogryposis-renal dysfunction-cholestasis syndrome.
Jang WY, Cho TJ, Bae JY, Jung HW, Ko JS, Park MS, Yoo WJ, Chung CY, Seo JK, Choi IH
J Pediatr Orthop 2011 Jan-Feb;31(1):107-12. doi: 10.1097/BPO.0b013e3182032c83. PMID: 21150740
Ichthyosis associated with ARC syndrome: ARC syndrome is one of the differential diagnoses of ichthyosis.
Choi HJ, Lee MW, Choi JH, Moon KC, Koh JK
Pediatr Dermatol 2005 Nov-Dec;22(6):539-42. doi: 10.1111/j.1525-1470.2005.00135.x. PMID: 16354257

Diagnosis

One case of arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome featuring an incomplete and mild phenotype.
Yu L, Li D, Zhang T, Xiao Y, Wang Y, Ge T
BMC Nephrol 2022 Jun 27;23(1):228. doi: 10.1186/s12882-022-02851-2. PMID: 35761207Free PMC Article
ARC syndrome.
Mutlu M, Aslan Y, Aktürk-Acar F, Çakır M, Erduran E, Kalyoncu M
Turk J Pediatr 2017;59(4):487-490. doi: 10.24953/turkjped.2017.04.019. PMID: 29624233
α-granule biogenesis: from disease to discovery.
Chen CH, Lo RW, Urban D, Pluthero FG, Kahr WH
Platelets 2017 Mar;28(2):147-154. Epub 2017 Feb 22 doi: 10.1080/09537104.2017.1280599. PMID: 28277061
Arthrogryposis-renal tubular dysfunction-cholestasis syndrome: a cause of neonatal cholestasis. Case report.
Ilhan O, Ozer EA, Ozdemir SA, Akbay S, Memur S, Kanar B, Tatli MM
Arch Argent Pediatr 2016 Feb;114(1):e9-12. doi: 10.5546/aap.2016.eng.e9. PMID: 26914089
Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome: from molecular genetics to clinical features.
Zhou Y, Zhang J
Ital J Pediatr 2014 Sep 20;40:77. doi: 10.1186/s13052-014-0077-3. PMID: 25239142Free PMC Article

Therapy

The Role of Platelets and ε-Aminocaproic Acid in Arthrogryposis, Renal Dysfunction, and Cholestasis (ARC) Syndrome Associated Hemorrhage.
Weyand AC, Lombel RM, Pipe SW, Shavit JA
Pediatr Blood Cancer 2016 Mar;63(3):561-3. Epub 2015 Oct 27 doi: 10.1002/pbc.25814. PMID: 26505894Free PMC Article
Liver transplant in a case of arthrogryposis-renal tubular dysfunction-cholestasis syndrome with severe intractable pruritus.
Dehghani SM, Bahador A, Nikeghbalian S, Salahi H, Geramizadeh B, Malekpour A, Malek-Hosseini SA
Exp Clin Transplant 2013 Jun;11(3):290-2. Epub 2012 Nov 22 doi: 10.6002/ect.2012.0202. PMID: 23190456
Ichthyosis associated with ARC syndrome: ARC syndrome is one of the differential diagnoses of ichthyosis.
Choi HJ, Lee MW, Choi JH, Moon KC, Koh JK
Pediatr Dermatol 2005 Nov-Dec;22(6):539-42. doi: 10.1111/j.1525-1470.2005.00135.x. PMID: 16354257
Liver biopsy complicated by hemorrhage in a patient with ARC syndrome.
Hayes JA, Kahr WH, Lo B, Macpherson BA
Paediatr Anaesth 2004 Nov;14(11):960-3. doi: 10.1111/j.1460-9592.2004.01301.x. PMID: 15500499
Arthrogryposis, renal dysfunction and cholestasis syndrome.
Abdullah MA, Al-Hasnan Z, Okamoto E, Abomelha AM
Saudi Med J 2000 Mar;21(3):297-9. PMID: 11533803

Prognosis

One case of arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome featuring an incomplete and mild phenotype.
Yu L, Li D, Zhang T, Xiao Y, Wang Y, Ge T
BMC Nephrol 2022 Jun 27;23(1):228. doi: 10.1186/s12882-022-02851-2. PMID: 35761207Free PMC Article
ARC syndrome.
Mutlu M, Aslan Y, Aktürk-Acar F, Çakır M, Erduran E, Kalyoncu M
Turk J Pediatr 2017;59(4):487-490. doi: 10.24953/turkjped.2017.04.019. PMID: 29624233
Autosomal Recessive Keratoderma-Ichthyosis-Deafness (ARKID) Syndrome Is Caused by VPS33B Mutations Affecting Rab Protein Interaction and Collagen Modification.
Gruber R, Rogerson C, Windpassinger C, Banushi B, Straatman-Iwanowska A, Hanley J, Forneris F, Strohal R, Ulz P, Crumrine D, Menon GK, Blunder S, Schmuth M, Müller T, Smith H, Mills K, Kroisel P, Janecke AR, Gissen P
J Invest Dermatol 2017 Apr;137(4):845-854. Epub 2016 Dec 23 doi: 10.1016/j.jid.2016.12.010. PMID: 28017832Free PMC Article
Arthrogryposis-renal tubular dysfunction-cholestasis syndrome: a cause of neonatal cholestasis. Case report.
Ilhan O, Ozer EA, Ozdemir SA, Akbay S, Memur S, Kanar B, Tatli MM
Arch Argent Pediatr 2016 Feb;114(1):e9-12. doi: 10.5546/aap.2016.eng.e9. PMID: 26914089
Arc syndrome without arthrogryposis, with hip dislocation and renal glomerulocystic appearance: a case report.
Arhan E, Yusufoğlu AM, Sayli TR
Eur J Pediatr 2009 Aug;168(8):995-8. Epub 2008 Oct 30 doi: 10.1007/s00431-008-0860-5. PMID: 18972129

Clinical prediction guides

The Sec1-Munc18 protein VPS33B forms a uniquely bidirectional complex with VPS16B.
Liu RJY, Al-Molieh Y, Chen SZ, Drobac M, Urban D, Chen CH, Yao HHY, Geng RSQ, Li L, Pluthero FG, Benlekbir S, Rubinstein JL, Kahr WHA
J Biol Chem 2023 Jun;299(6):104718. Epub 2023 Apr 14 doi: 10.1016/j.jbc.2023.104718. PMID: 37062417Free PMC Article
One case of arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome featuring an incomplete and mild phenotype.
Yu L, Li D, Zhang T, Xiao Y, Wang Y, Ge T
BMC Nephrol 2022 Jun 27;23(1):228. doi: 10.1186/s12882-022-02851-2. PMID: 35761207Free PMC Article
Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome: a rare association with high GGT level and absent kidney.
Gupta V, Pandita A, Panghal A, Kallem V
BMJ Case Rep 2018 Aug 9;2018 doi: 10.1136/bcr-2017-223715. PMID: 30093463Free PMC Article
ARC syndrome with high GGT cholestasis caused by VPS33B mutations.
Wang JS, Zhao J, Li LT
World J Gastroenterol 2014 Apr 28;20(16):4830-4. doi: 10.3748/wjg.v20.i16.4830. PMID: 24782640Free PMC Article
VPS33B mutation with ichthyosis, cholestasis, and renal dysfunction but without arthrogryposis: incomplete ARC syndrome phenotype.
Bull LN, Mahmoodi V, Baker AJ, Jones R, Strautnieks SS, Thompson RJ, Knisely AS
J Pediatr 2006 Feb;148(2):269-71. doi: 10.1016/j.jpeds.2005.10.005. PMID: 16492441

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