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Joubert syndrome with oculorenal defect

MedGen UID:
340930
Concept ID:
C1855675
Disease or Syndrome
Synonyms: Arima syndrome; Cerebro-oculo-hepato-renal syndrome; Chorioretinal coloboma with cerebellar vermis aplasia; Dekaban Arima syndrome; Joubert syndrome with bilateral chorioretinal coloboma
SNOMED CT: Joubert syndrome with oculorenal defect (721862000); Arima syndrome (721862000); Cerebello-oculo-renal syndrome (721862000)
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).
 
Monarch Initiative: MONDO:0009480
OMIM®: 243910
Orphanet: ORPHA2318

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

Additional description

From OMIM
Arima syndrome is an autosomal recessive disorder characterized by agenesis of the cerebellar vermis, ocular abnormalities, cystic kidney disease, and, in some cases, liver disease. It shares phenotypic features with Joubert syndrome (see 213300), COACH syndrome (see 216360), and familial juvenile nephronophthisis (see 256100).  http://www.omim.org/entry/243910

Clinical features

From HPO
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine).
Polycystic kidney disease
MedGen UID:
9639
Concept ID:
C0022680
Disease or Syndrome
The presence of multiple cysts in both kidneys.
Polyuria
MedGen UID:
19404
Concept ID:
C0032617
Sign or Symptom
An increased rate of urine production.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Nephronophthisis
MedGen UID:
146912
Concept ID:
C0687120
Disease or Syndrome
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recognized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia, and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype, inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
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.
Renal corticomedullary cysts
MedGen UID:
409631
Concept ID:
C1968619
Disease or Syndrome
The presence of multiple cysts at the border between the renal cortex and medulla.
Tubulointerstitial fibrosis
MedGen UID:
370652
Concept ID:
C1969372
Disease or Syndrome
A progressive detrimental connective tissue deposition (fibrosis) on the kidney parenchyma involving the tubules and interstitial tissue of the kidney. Tubulointerstitial injury in the kidney is complex, involving a number of independent and overlapping cellular and molecular pathways, with renal interstitial fibrosis and tubular atrophy (IF/TA) as the final common pathway. However, IF and TA are separable, as shown by the profound TA in renal artery stenosis, which characteristically has little or no fibrosis (or inflammation). For new annotations it is preferable to annotate to the specific HPO terms for Renal interstitial fibrosis and/or Renal tubular atrophy.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Renal sodium wasting
MedGen UID:
440580
Concept ID:
C2748576
Finding
An abnormally increased sodium concentration in the urine in the presence of hyponatremia.
Postaxial hand polydactyly
MedGen UID:
609221
Concept ID:
C0431904
Congenital Abnormality
Supernumerary digits located at the ulnar side of the hand (that is, on the side with the fifth finger).
Postaxial foot polydactyly
MedGen UID:
384489
Concept ID:
C2112129
Finding
Polydactyly of the foot most commonly refers to the presence of six toes on one foot. Postaxial polydactyly affects the lateral ray and the duplication may range from a well-formed articulated digit to a rudimentary digit.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Esophageal varix
MedGen UID:
5027
Concept ID:
C0014867
Disease or Syndrome
Extreme dilation of the submucusoal veins in the lower portion of the esophagus.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Hepatic fibrosis
MedGen UID:
116093
Concept ID:
C0239946
Disease or Syndrome
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
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).
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Polydipsia
MedGen UID:
43214
Concept ID:
C0085602
Sign or Symptom
Excessive thirst manifested by excessive fluid intake.
Gray matter heterotopia
MedGen UID:
452349
Concept ID:
C0266491
Finding
Heterotopia or neuronal heterotopia are macroscopic clusters of misplaced neurons (gray matter), most often situated along the ventricular walls or within the subcortical white matter.
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.
Cerebellar vermis hypoplasia
MedGen UID:
333548
Concept ID:
C1840379
Finding
Underdevelopment of the vermis of cerebellum.
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Intellectual disability, progressive
MedGen UID:
337397
Concept ID:
C1846149
Mental or Behavioral Dysfunction
The term progressive intellectual disability should be used if intelligence decreases/deteriorates over time.
Dilated fourth ventricle
MedGen UID:
376050
Concept ID:
C1847117
Finding
An abnormal dilatation of the fourth cerebral ventricle.
Occipital meningocele
MedGen UID:
336389
Concept ID:
C1848652
Disease or Syndrome
A herniation of meninges through a congenital bone defect in the skull in the occipital region.
Brainstem dysplasia
MedGen UID:
383739
Concept ID:
C1855677
Congenital Abnormality
A developmental structural anomaly of the stalk-like part of the brain that comprises the midbrain (aka mesencephalon), the pons (aka pons Varolii), and the medulla oblongata, and connects the cerebral hemispheres with the cervical spinal cord.
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.
Agenesis of cerebellar vermis
MedGen UID:
1768774
Concept ID:
C5437781
Congenital Abnormality
Congenital absence of the vermis of cerebellum.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
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).
Dyspnea
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.
Tachypnea
MedGen UID:
66669
Concept ID:
C0231835
Finding
Very rapid breathing.
Wide mouth
MedGen UID:
44238
Concept ID:
C0024433
Congenital Abnormality
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
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.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Chorioretinal coloboma
MedGen UID:
66820
Concept ID:
C0240896
Congenital Abnormality
Absence of a region of the retina, retinal pigment epithelium, and choroid.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Disease or Syndrome
Blindness is the condition of lacking visual perception defined as visual perception below 3/60 and/or a visual field of no greater than 10 degrees in radius around central fixation.
Retinal dystrophy
MedGen UID:
208903
Concept ID:
C0854723
Finding
Retinal dystrophy is an abnormality of the retina associated with a hereditary process. Retinal dystrophies are defined by their predominantly monogenic inheritance and they are frequently associated with loss or dysfunction of photoreceptor cells as a primary or secondary event.
Undetectable electroretinogram
MedGen UID:
383742
Concept ID:
C1855685
Finding
Lack of any response to stimulation upon electroretinography.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVJoubert syndrome with oculorenal defect

Professional guidelines

Curated

Valente EM, Brancati F, Boltshauser E, Dallapiccola B
Eur J Hum Genet 2011 Sep;19(9) Epub 2011 Mar 30 doi: 10.1038/ejhg.2011.49. PMID: 21448235Free PMC Article

Recent clinical studies

Etiology

Brancati F, Dallapiccola B, Valente EM
Orphanet J Rare Dis 2010 Jul 8;5:20. doi: 10.1186/1750-1172-5-20. PMID: 20615230Free PMC Article
Brancati F, Barrano G, Silhavy JL, Marsh SE, Travaglini L, Bielas SL, Amorini M, Zablocka D, Kayserili H, Al-Gazali L, Bertini E, Boltshauser E, D'Hooghe M, Fazzi E, Fenerci EY, Hennekam RC, Kiss A, Lees MM, Marco E, Phadke SR, Rigoli L, Romano S, Salpietro CD, Sherr EH, Signorini S, Stromme P, Stuart B, Sztriha L, Viskochil DH, Yuksel A, Dallapiccola B; International JSRD Study Group, Valente EM, Gleeson JG
Am J Hum Genet 2007 Jul;81(1):104-13. Epub 2007 May 18 doi: 10.1086/519026. PMID: 17564967Free PMC Article

Diagnosis

Koyama S, Sato H, Wada M, Kawanami T, Emi M, Kato T
BMC Med Genet 2017 Mar 27;18(1):37. doi: 10.1186/s12881-017-0399-2. PMID: 28347285Free PMC Article
Brancati F, Dallapiccola B, Valente EM
Orphanet J Rare Dis 2010 Jul 8;5:20. doi: 10.1186/1750-1172-5-20. PMID: 20615230Free PMC Article
Brancati F, Barrano G, Silhavy JL, Marsh SE, Travaglini L, Bielas SL, Amorini M, Zablocka D, Kayserili H, Al-Gazali L, Bertini E, Boltshauser E, D'Hooghe M, Fazzi E, Fenerci EY, Hennekam RC, Kiss A, Lees MM, Marco E, Phadke SR, Rigoli L, Romano S, Salpietro CD, Sherr EH, Signorini S, Stromme P, Stuart B, Sztriha L, Viskochil DH, Yuksel A, Dallapiccola B; International JSRD Study Group, Valente EM, Gleeson JG
Am J Hum Genet 2007 Jul;81(1):104-13. Epub 2007 May 18 doi: 10.1086/519026. PMID: 17564967Free PMC Article

Prognosis

Koyama S, Sato H, Wada M, Kawanami T, Emi M, Kato T
BMC Med Genet 2017 Mar 27;18(1):37. doi: 10.1186/s12881-017-0399-2. PMID: 28347285Free PMC Article
Brancati F, Dallapiccola B, Valente EM
Orphanet J Rare Dis 2010 Jul 8;5:20. doi: 10.1186/1750-1172-5-20. PMID: 20615230Free PMC Article

Clinical prediction guides

Koyama S, Sato H, Wada M, Kawanami T, Emi M, Kato T
BMC Med Genet 2017 Mar 27;18(1):37. doi: 10.1186/s12881-017-0399-2. PMID: 28347285Free PMC Article
Keeler LC, Marsh SE, Leeflang EP, Woods CG, Sztriha L, Al-Gazali L, Gururaj A, Gleeson JG
Am J Hum Genet 2003 Sep;73(3):656-62. Epub 2003 Aug 13 doi: 10.1086/378206. PMID: 12917796Free PMC Article

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