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Year : 2022  |  Volume : 7  |  Issue : 2  |  Page : 78-80

Joubert syndrome presented as chronic kidney disease: A rare event

Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Date of Submission27-Jul-2022
Date of Acceptance14-Aug-2022
Date of Web Publication22-Nov-2022

Correspondence Address:
Dr. Abdullah Al Mamun
Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University, Dhaka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pnjb.pnjb_19_22

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Joubert syndrome (JS) is a rare disorder affecting the multisystem of the body. It involves defects in the cerebellar vermis, abnormal eye movement, renal aplasia/hypoplasia, and polydactyle. Here is a report of a 9-year-old boy suffering from JS presented as chronic kidney disease.

Keywords: Children, CKD, Joubert syndrome

How to cite this article:
Mamun AA, Santa SM, Jesmin T, Sharmim MS, Huque SS, Roy RR, Begum A. Joubert syndrome presented as chronic kidney disease: A rare event. Paediatr Nephrol J Bangladesh 2022;7:78-80

How to cite this URL:
Mamun AA, Santa SM, Jesmin T, Sharmim MS, Huque SS, Roy RR, Begum A. Joubert syndrome presented as chronic kidney disease: A rare event. Paediatr Nephrol J Bangladesh [serial online] 2022 [cited 2023 Oct 4];7:78-80. Available from: http://www.pnjb-online.org/text.asp?2022/7/2/78/361618

  Introduction Top

Joubert syndrome (JS) is a rare autosomal recessive neurological disorder named after Marie Joubert, who recognized the association of developmental defects of the cerebellar vermis with mental retardation, episodic hyperpnea, and abnormal eye movements.[1] Joubert et al.[2] recognized this syndrome in four siblings and one sporadic case. JS is under-reported with a prevalence of less than 1 in 100,000. By 2009, only 200 cases have been reported all over the world.[3]

JS is clinically heterogeneous and is characterized by multiple organ involvement, nephronophthisis (NPHP), or cystic dysplasia, in association with retinal degeneration, aplasia/hypoplasia of the cerebellar vermis causing ataxia, facultative symptoms of psychomotor retardation, and polydactyly.[4] Renal involvement has been described in 25%–30% of patients with JS.[5] Other physical deformities that may be present in JS are polydactyly, cleft lip or palate, tongue abnormalities, hypotonia, encephalocele, meningocele, hydrocephalus, kidney problems, pituitary abnormality, and autistic-like behavior. Seizures may also occur. Some children have a mild form of the disorder, with minimal motor disability and good mental development, whereas others may have a severe motor disability and moderate mental retardation.[5] Most cases of JS are sporadic; however, in some families, JS appears to be inherited via a recessive gene. The specific gene was recently located on chromosome 6q23.2-q23.3[6] with the availability of neonatal magnetic resonance imaging (MRI), which is quite feasible to make a diagnosis in the neonatal period.[6] Due to rarity, here we present a 9-year-old boy with JS who presented to us with chronic kidney disease (CKD).

  Case Report Top

A 9-year-old boy [Figure 1], second issue of non-consanguineous parents, was admitted to the Pediatric Nephrology Department of Bangabandhu Sheikh Mujib Medical University with the complaints of raised serum creatinine for the last 3 months. He was diagnosed as a case of JS at 5 years of age based on global developmental delay, mental retardation (WISC-R psychological assessment; moderate impairment in intellectual functioning level) from early childhood, intellectual disability, walking difficulty, occasional aggressive behavior, squint and finding of the hypoplastic cerebellar vermis with elongated superior cerebellar peduncles and molar tooth sign (MTS) of midbrain on MRI of the brain which was suggestive of JS. On examination, he has a global developmental delay, oculomotor apraxia, high arched eyebrows, and hypertelorism. Anthropometry showed severe underweight (15 kg; WAZ = –4.5) and severely stunted (111 cm; HAZ = –4.2); body surface area was 0.66 m2.
Figure 1: Smiling face of the patient

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Biochemical profile showed anemia (Hb 9.5 g/dL), impaired renal function (serum creatinine 2.4 mg/dL, eGFR 19.10 mL/ min/1.73 m2, blood urea 189.2 mg/dL), serum calcium 11.3 mg/dL, serum inorganic phosphate 4.6 mg/dL, parathyroid hormone [PTH] 6 pg/mL, and vitamin D 43.58 ng/mL). Serum electrolytes showed sodium 133 mmol/ L, potassium 3.1 mmol/ L, chloride 103 mmol/L, and T-CO2 25.7 mmol/L. Ultrasonography of kidneys, ureters, and bladder (KUB) revealed the bipolar length of both kidneys was in the lower limit (right kidney 7.8 cm and left kidney 8.0 cm), with increased cortical echogenicity and poor cortico-medullary differentiation.

The pediatric endocrinologist examined the patient thoroughly and found tanner stage I (prepubertal), which was quite normal at this age and advised to follow up the patient up to puberty and advised to visit a pediatric endocrinologist if puberty does not occur up to 14–15 years of age. The pediatric neurologist advised developmental therapy including drug therapy with levocarnitin, mecobalamine, and follow-up with electroencephalogram.

Ophthalmological examination revealed mild pallor of the optic disk with mild generalized attenuation of blood vessels in both eyes on fundus examination.

Therefore, he was diagnosed with a case of Joubert syndrome and related disorder (JSRD) with CKD stage IV with adynamic bone disease (serum calcium 11.3 mg/dL’ PTH 6 pg/mL and IPo4 4.6 mg/dL) and discontinued the active vitamin D. Other conservative management of CKD was continued with sodium bicarbonate, sevelamer, vitamins and minerals, and subcutaneous erythropoietin.

  Discussion Top

JSRDs are a genetically heterogeneous group of disorders and are classified into six different phenotypic subgroups: pure JS, JS with ocular defect, JS with renal defect, JS with oculorenal defects, JS with a hepatic defect, and JS with orofaciodigital defects.[7]

MTS is characteristic but not pathognomonic of JS, as it is also seen in Varadi–Papp syndrome, Malta syndrome, Senior–Loken syndrome, Dekaban–Arima syndrome, JS with polymicrogyria, pontine tegmental cap dysplasia, and COACH syndrome[8],[9] [Table 1].
Table 1: Differential diagnosis of JS[10]

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Our patient presented with the characteristic feature of JSRD such as global developmental delay, mental retardation from early childhood, intellectual disability, walking difficulty, occasional aggressive behavior, squint, and finding of the hypoplastic cerebellar vermis with elongated superior cerebellar peduncles and MTS of midbrain on MRI of the brain which was suggestive of JS which is similar to many other reported case.[11] But the interesting fact is that the patient did not have any renal involvement at the time of presentation.

Another interesting fact is that we did not find any feature of NPHP or cystic change in the kidney.[12] Though, subsequent investigation revealed, concentrating disability (serum osmolality 313 mOsmol/kg and urine osmolality 199 mOsmol/kg), it might be due to early feature of CKD. Brancati et al.[7] also describe some structural tubulointerstitial disorders, which might be characterized by irregular, thickened basal membrane of the tubular epithelium and progressive interstitial fibrosis.

More than 10 causative genes have been identified: JBTS1/INPP5E [OMIM*613037], JBTS2/TMEM216 [OMIM*613277], JBTS3/AHI1 [OMIM*608894], JBTS4/NPHP1 [OMIM* 607100], JBTS5/CEP290 [OMIM*610142], JBTS6/TME M67 [OMIM*609884], JBTS7/RPGRIP1L [OMIM*61 0937], JBTS8/ARL13B [OMIM*608922], JBTS9/CC2D2A [OMIM*612013], and JBTS10/OFD1 [OMIM*300170].[13] But we could not perform any genetic test to our patient due to lack of genetic testing facility in our center.

There is no cure for JS. Treatment is symptomatic and supportive. A multidisciplinary approach including infant stimulation and physical, occupational, and speech therapy may benefit some children. Infants with abnormal breathing patterns should be monitored. Rehabilitation strategies must be planned for cognitive and behavioral difficulties and specific manifestations such as the visual impairment.[14]

The prognosis of JS cases is multifactorial. If discovered and managed early through implementing an intervention program for patients including special education, occupational, physical, and speech therapy. Feeding difficulties may represent a problem for a number of patients. Afterward, prognosis depends mostly on renal and hepatic complications and can contribute as major causes of death in patients with JSRD if not properly taken care of.[14],[15]

  Conclusion Top

JS is a rare disorder but can be diagnosed with a strong suspicion and knowing the clinical criteria. Treatment approach is multidisciplinary and the prognosis depends on the age of presentation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Not applicable.

Conflicts of interest

There are no conflicts of interest.

  References Top

Joubert M, Eisenring JJ, Robb JP, Andermann F Familial agenesis of the cerebellar vermis: A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology 1969;19:813-25.  Back to cited text no. 1
Bainade KS, Kotrashetti VA, Sonawane VB, Vatakar A, Bhatarkar SR Joubert’s syndrome: A case report. Int J Contemp Pediatr 2020;7:2068-71.  Back to cited text no. 2
Choh SA, Choh NA, Bhat SA, Jehangir M MRI findings in Joubert syndrome. Indian J Pediatr 2009;76:231-5.  Back to cited text no. 3
Lacquaniti A, Chirico V, Donato V, Briuglia S, Cernaro V, Gallizzi R, et al. NGAL as an early biomarker of kidney disease in Joubert syndrome: Three brothers compared. Ren Fail 2012;34:495-8.  Back to cited text no. 4
Shamsudheen MP, Das U, Taduri G, Guditi S, Karthik R, Thakur R A case of Joubert syndrome with chronic kidney disease. Indian J Nephrol 2021;31:61-3.  Back to cited text no. 5
Akcakus M, Gunes T, Kumandas S, Kurtoglu S, Coskun A Joubert syndrome: Report of a neonatal case. Paediatr Child Health 2003;8:499-502.  Back to cited text no. 6
Brancati F, Dallapiccola B, Valente EM Joubert syndrome and related disorders. Orphanet J Rare Dis 2010;5:20.  Back to cited text no. 7
Singh P, Goraya JS, Saggar K, Ahluwalia A A report of Joubert syndrome in an infant, with literature review. J Pediatr Neurosci 2011;6:44-7.  Back to cited text no. 8
Hiremath R, Manswini P, Ramesh P, Ramesh P, Rudrappa K Molar tooth sign in Joubert’s syndrome: A case report. J Clin Diagn Res 2011;5:880-1.  Back to cited text no. 9
Venkataramaiah VD, Patil AT, Sathyanarayana VH Joubert syndrome in siblings: A rare case report with literature review. Apollo Med 2017;14:185-7.  Back to cited text no. 10
Bennett CL, Meuleman J, Chance PF, Glass IA Clinical and genetic aspects of the Joubert syndrome: A disorder characterized by cerebellar Vermian hypoplasia and accompanying brainstem malformations. Curr Genomics 2003;4:123-9.  Back to cited text no. 11
Gleeson JG, Keller LC, Parisi MA, Marsh SE, Chance PF, Glass IA, et al. Molar tooth sign of the Midbrain–Hindbrain junction: Occurrence in multiple distinct syndromes. Am J Med Genet 2004;125:125-34.  Back to cited text no. 12
Assadi F Lack of NPHP2 mutations in a newborn infant with Joubert syndrome-related disorder presenting as end-stage renal disease. Pediatr Nephrol 2007;22:750-2.  Back to cited text no. 13
Brancati F, Dallapiccola B, Valente EM Joubert syndrome and related disorders. Orphanet J Rare Dis 2010;5:20.  Back to cited text no. 14
Parisi MA Clinical and molecular features of Joubert syndrome and related disorders. Am J Med Genet C Semin Med Genet 2009;151C:326-40.  Back to cited text no. 15


  [Figure 1]

  [Table 1]


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