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Arthrogryposis, renal dysfunction, and cholestasis 1(ARCS1)

MedGen UID:
347219
Concept ID:
C1859722
Disease or Syndrome
Synonyms: ARCS1; VPS33B-Related Arthrogryposis, Renal Dysfunction, and Cholestasis Syndrome
 
Gene (location): VPS33B (15q26.1)
 
Monarch Initiative: MONDO:0008822
OMIM®: 208085

Definition

Any arthrogryposis-renal dysfunction-cholestasis syndrome in which the cause of the disease is a mutation in the VPS33B gene. [from MONDO]

Clinical features

From HPO
Kidney disorder
MedGen UID:
9635
Concept ID:
C0022658
Disease or Syndrome
A nonspecific term referring to disease or damage of the kidneys.
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Aminoaciduria
MedGen UID:
116067
Concept ID:
C0238621
Disease or Syndrome
An increased concentration of an amino acid in the urine.
Renal tubular atrophy
MedGen UID:
388054
Concept ID:
C1858395
Finding
The presence of renal tubules with thick redundant basement membranes, or a reduction of greater than 50% in tubular diameter compared to surrounding non-atrophic tubules.
Reduced renal corticomedullary differentiation
MedGen UID:
813461
Concept ID:
C3807131
Finding
Reduced differentiation between renal cortex and medulla on diagnostic imaging.
Talipes calcaneovalgus
MedGen UID:
56270
Concept ID:
C0152237
Anatomical Abnormality
Talipes calcaneovalgus is a flexible foot deformity (as opposed to a rigid congenital vertical talus foot deformity) that can either present as a positional or structural foot deformity depending on severity and/or causality. The axis of calcaneovalgus deformity is in the tibiotalar joint, where the foot is positioned in extreme hyperextension. On inspection, the foot has an "up and out" appearance, with the dorsal forefoot practically touching the anterior aspect of the ankle and lower leg.
Patent foramen ovale
MedGen UID:
8891
Concept ID:
C0016522
Congenital Abnormality
Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.
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.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Right ventricular hypertrophy
MedGen UID:
57981
Concept ID:
C0162770
Disease or Syndrome
In this case the right ventricle is more muscular than normal, causing a characteristic boot-shaped (coeur-en-sabot) appearance as seen on anterior- posterior chest x-rays. Right ventricular hypertrophy is commonly associated with any form of right ventricular outflow obstruction or pulmonary hypertension, which may in turn owe its origin to left-sided disease. The echocardiographic signs are thickening of the anterior right ventricular wall and the septum. Cavity size is usually normal, or slightly enlarged. In many cases there is associated volume overload present due to tricuspid regurgitation, in the absence of this, septal motion is normal.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Giant cell hepatitis
MedGen UID:
45030
Concept ID:
C0027613
Disease or Syndrome
Chronic hepatitis characterized by parenchymal inflammation with formation of large multinucleated hepatocytes in response to a variety of insults to the liver.
Cholestatic liver disease
MedGen UID:
163651
Concept ID:
C0860204
Disease or Syndrome
Intrahepatic biliary atresia
MedGen UID:
343308
Concept ID:
C1855284
Disease or Syndrome
Atresia in the intrahepatic bile duct.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Lissencephaly
MedGen UID:
78604
Concept ID:
C0266463
Finding
A spectrum of malformations of cortical development caused by insufficient neuronal migration that subsumes the terms agyria, pachygyria and subcortical band heterotopia. See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly.
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.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Abnormal bleeding
MedGen UID:
264316
Concept ID:
C1458140
Pathologic Function
An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects.
Arthrogryposis multiplex congenita
MedGen UID:
2455
Concept ID:
C0003886
Finding
Multiple congenital contractures in different body areas.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
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.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Hip dysplasia
MedGen UID:
1640560
Concept ID:
C4551649
Congenital Abnormality
The presence of developmental dysplasia of the hip.
Renal tubular acidosis
MedGen UID:
90
Concept ID:
C0001126
Disease or Syndrome
Acidosis owing to malfunction of the kidney tubules with accumulation of metabolic acids and hyperchloremia, potentially leading to complications including hypokalemia, hypercalcinuria, nephrolithiasis and nephrocalcinosis.
Dehydration
MedGen UID:
8273
Concept ID:
C0011175
Disease or Syndrome
A condition resulting from the excessive loss of water from the body. It is usually caused by severe diarrhea, vomiting or diaphoresis.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.
Conjugated hyperbilirubinemia
MedGen UID:
82787
Concept ID:
C0268307
Disease or Syndrome
Abnormally high level of conjugated bilirubin in the blood.
Elevated hepatic transaminase
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Elevated gamma-glutamyltransferase level
MedGen UID:
1370086
Concept ID:
C4476869
Finding
Increased level of the enzyme gamma-glutamyltransferase (GGT). GGT is mainly present in kidney, liver, and pancreatic cells, but small amounts are present in other tissues.
Sloping forehead
MedGen UID:
346640
Concept ID:
C1857679
Finding
Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.
Ichthyosis
MedGen UID:
7002
Concept ID:
C0020757
Disease or Syndrome
An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.
Nephrogenic diabetes insipidus
MedGen UID:
57876
Concept ID:
C0162283
Disease or Syndrome
Hereditary nephrogenic diabetes insipidus (NDI) is characterized by inability to concentrate the urine, which results in polyuria (excessive urine production) and polydipsia (excessive thirst). Affected untreated infants usually have poor feeding and failure to thrive, and rapid onset of severe dehydration with illness, hot environment, or the withholding of water. Short stature and secondary dilatation of the ureters and bladder from the high urine volume is common in untreated individuals.

Recent clinical studies

Etiology

Adamczyk-Gruszka O, Horecka-Lewitowicz A, Zmelonek-Znamirowska A, Gruszka J, Koziel D, Lewitowicz P
Am J Case Rep 2021 Sep 17;22:e932769. doi: 10.12659/AJCR.932769. PMID: 34531360Free PMC Article
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
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

Diagnosis

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
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
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
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
Zhou Y, Zhang J
Ital J Pediatr 2014 Sep 20;40:77. doi: 10.1186/s13052-014-0077-3. PMID: 25239142Free PMC Article

Therapy

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
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

Prognosis

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
Adamczyk-Gruszka O, Horecka-Lewitowicz A, Zmelonek-Znamirowska A, Gruszka J, Koziel D, Lewitowicz P
Am J Case Rep 2021 Sep 17;22:e932769. doi: 10.12659/AJCR.932769. PMID: 34531360Free PMC Article
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
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
Seo SH, Hwang SM, Ko JM, Ko JS, Hyun YJ, Cho SI, Park H, Kim SY, Seong MW, Park SS
Clin Genet 2015 Jul;88(1):80-4. Epub 2014 Aug 7 doi: 10.1111/cge.12442. PMID: 24917129

Clinical prediction guides

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
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
Adamczyk-Gruszka O, Horecka-Lewitowicz A, Zmelonek-Znamirowska A, Gruszka J, Koziel D, Lewitowicz P
Am J Case Rep 2021 Sep 17;22:e932769. doi: 10.12659/AJCR.932769. PMID: 34531360Free PMC Article
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
Seo SH, Hwang SM, Ko JM, Ko JS, Hyun YJ, Cho SI, Park H, Kim SY, Seong MW, Park SS
Clin Genet 2015 Jul;88(1):80-4. Epub 2014 Aug 7 doi: 10.1111/cge.12442. PMID: 24917129

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