PDF icon Download PDF
Journal of Pediatric Neurology 2023; 21(01): 053-057
DOI: 10.1055/s-0042-1759532
Review Article

Joubert Syndrome: Diagnostic Evaluation and Follow-up

Caterina Cuppari
1   Unit of Pediatric Emergency, Department of Human Pathology of the Adult and Developmental Age “Gaetano Barresi,” University of Messina, Messina, Italy
,
Ida Ceravolo
2   Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
,
Alessio Mancuso
1   Unit of Pediatric Emergency, Department of Human Pathology of the Adult and Developmental Age “Gaetano Barresi,” University of Messina, Messina, Italy
,
Giovanni Farello
3   Pediatric Clinic–Department of Life, Health and Environmental Sciences–Piazzale Salvatore, Coppito (AQ), Italy
,
Giulia Iapadre
4   Department of Pediatrics, University of L'Aquila, Via Vetoio, L'Aquila, Italy
,
Luca Zagaroli
4   Department of Pediatrics, University of L'Aquila, Via Vetoio, L'Aquila, Italy
,
Giuliana Nanni
4   Department of Pediatrics, University of L'Aquila, Via Vetoio, L'Aquila, Italy
,
Maria Domenica Ceravolo
1   Unit of Pediatric Emergency, Department of Human Pathology of the Adult and Developmental Age “Gaetano Barresi,” University of Messina, Messina, Italy
› Author Affiliations
› Further Information
Also available ateRef
  Permissions and Reprints
Preview

Abstract

The follow-up of a child with genetic syndrome is necessarily multidisciplinary because of the multiplicity of problems and calls for close collaboration between different specialists. The primary objective is the total care of the child and his family, regardless of the rarity and complexity of the disease, to obtain the highest possible degree of mental and physical health and autonomy.

Keywords

molar tooth sign - ciliopathies - developmental delay

Author Contributions

Conceptualization: C. C.


Investigation: C. C., I. C.


Resources: E. G.


Data curation: A. M., G. N.


Writing - original draft preparation: G. F.


Writing - review and editing: G. I., M. D. C.


Supervision: L. Z.


All authors have read and agreed to the published version of the manuscript.


Data Availability Statement

The data presented in this study are available on request from the corresponding author.




Publication History

Received: 22 August 2022

Accepted: 27 October 2022

Article published online:
26 December 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Valente EM, Salpietro DC, Brancati F. et al. Description, nomenclature, and mapping of a novel cerebello-renal syndrome with the molar tooth malformation. Am J Hum Genet 2003; 73 (03) 663-670
    Search in Google Scholar
  • 2 Shaheen R, Mark P, Prevost CT. et al. Biallelic variants in CTU2 cause DREAM-PL syndrome and impair thiolation of tRNA wobble U34. [published correction appears in Hum Mutat. 2021;42(2):219] Hum Mutat 2019; 40 (11) 2108-2120
    Search in Google Scholar
  • 3 Savasta S, Rossi A, Foiadelli T. et al. Melkersson−Rosenthal syndrome in childhood: report of three paediatric cases and a review of the literature. Int J Environ Res Public Health 2019; 16 (07) 1289
    Search in Google Scholar
  • 4 Toldo I, Brunello F, Morao V. et al. First attack and clinical presentation of hemiplegic migraine in pediatric age: a multicenter retrospective study and literature review. Front Neurol 2019; 10: 1079
    Search in Google Scholar
  • 5 Brancati F, Barrano G, Silhavy JL. et al; International JSRD Study Group. CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders. Am J Hum Genet 2007; 81 (01) 104-113
    Search in Google Scholar
  • 6 Brancati F, Travaglini L, Zablocka D. et al; International JSRD Study Group. RPGRIP1L mutations are mainly associated with the cerebello-renal phenotype of Joubert syndrome-related disorders. Clin Genet 2008; 74 (02) 164-170
    Search in Google Scholar
  • 7 Al-Gazali LI, Sztriha L, Punnose J, Shather W, Nork M. Absent pituitary gland and hypoplasia of the cerebellar vermis associated with partial ophthalmoplegia and postaxial polydactyly: a variant of orofaciodigital syndrome VI or a new syndrome?. J Med Genet 1999; 36 (02) 161-166
    Search in Google Scholar
  • 8 Matricardi S, Farello G, Savasta S, Verrotti A. Understanding childhood neuroimmune diseases of the central nervous system. Front Pediatr 2019; 7: 511
    Search in Google Scholar
  • 9 Maria BL, Bozorgmanesh A, Kimmel KN, Theriaque D, Quisling RG. Quantitative assessment of brainstem development in Joubert syndrome and Dandy-Walker syndrome. J Child Neurol 2001; 16 (10) 751-758
    Search in Google Scholar
  • 10 Greco M, Ferrara P, Farello G, Striano P, Verrotti A. Electroclinical features of epilepsy associated with 1p36 deletion syndrome: a review. Epilepsy Res 2018; 139: 92-101
    Search in Google Scholar
  • 11 Carotenuto M, Roccella M, Pisani F. et al. Polysomnographic findings in fragile X syndrome children with EEG abnormalities. Behav Neurol 2019; 2019: 5202808
    Search in Google Scholar
  • 12 Stagi S, Scalini P, Farello G, Verrotti A. Possible effects of an early diagnosis and treatment in patients with growth hormone deficiency: the state of art. Ital J Pediatr 2017; 43 (01) 81
    Search in Google Scholar
  • 13 İpek Ö, Akyolcu Ö, Bayar B. Physiotherapy and rehabilitation in a child with Joubert syndrome. Case Rep Pediatr 2017; 2017: 8076494
    Search in Google Scholar
  • 14 Kamdar BB, Nandkumar P, Krishnan V, Gamaldo CE, Collop NA. Self-reported sleep and breathing disturbances in Joubert syndrome. Pediatr Neurol 2011; 45 (06) 395-399
    Search in Google Scholar
  • 15 Gregory-Evans CY, Williams MJ, Halford S, Gregory-Evans K. Ocular coloboma: a reassessment in the age of molecular neuroscience. J Med Genet 2004; 41 (12) 881-891
    Search in Google Scholar
  • 16 Satran D, Pierpont ME, Dobyns WB. Cerebello-oculo-renal syndromes including Arima, Senior-Löken and COACH syndromes: more than just variants of Joubert syndrome. Am J Med Genet 1999; 86 (05) 459-469
    Search in Google Scholar
  • 17 Salomon R, Saunier S, Niaudet P. Nephronophthisis. Pediatr Nephrol 2009; 24 (12) 2333-2344
    Search in Google Scholar
  • 18 Brancati F, Iannicelli M, Travaglini L. et al; International JSRD Study Group. MKS3/TMEM67 mutations are a major cause of COACH Syndrome, a Joubert Syndrome related disorder with liver involvement. Hum Mutat 2009; 30 (02) E432-E442
    Search in Google Scholar
  • 19 Brancati F, Dallapiccola B, Valente EM. Joubert syndrome and related disorders. Orphanet J Rare Dis 2010; 5: 20
    Search in Google Scholar
  • 20 Manti S, Marseglia L, D'Angelo G. et al. Portal hypertension as immune mediate disease. Hepat Mon 2014; 14 (06) e18625
    Search in Google Scholar
  • 21 Pellegrino JE, Lensch MW, Muenke M, Chance PF. Clinical and molecular analysis in Joubert syndrome. Am J Med Genet 1997; 72 (01) 59-62
    Search in Google Scholar
  • 22 Chance PF, Cavalier L, Satran D, Pellegrino JE, Koenig M, Dobyns WB. Clinical nosologic and genetic aspects of Joubert and related syndromes. J Child Neurol 1999; 14 (10) 660-666 , discussion 669–672
    Search in Google Scholar
  • 23 Elmali M, Ozmen Z, Ceyhun M, Tokatlioğlu O, Incesu L, Diren B. Joubert syndrome with atrial septal defect and persistent left superior vena cava. Diagn Interv Radiol 2007; 13 (02) 94-96
    Search in Google Scholar
  • 24 Travaglini L, Brancati F, Attie-Bitach T. et al; International JSRD Study Group. Expanding CEP290 mutational spectrum in ciliopathies. Am J Med Genet A 2009; 149A (10) 2173-2180
    Search in Google Scholar
  • 25 Travaglini L, Brancati F, Silhavy J. et al; International JSRD Study Group. Phenotypic spectrum and prevalence of INPP5E mutations in Joubert syndrome and related disorders. Eur J Hum Genet 2013; 21 (10) 1074-1078
    Search in Google Scholar
  • 26 Iannicelli M, Brancati F, Mougou-Zerelli S. et al; International JSRD Study Group. Novel TMEM67 mutations and genotype-phenotype correlates in meckelin-related ciliopathies. Hum Mutat 2010; 31 (05) E1319-E1331
    Search in Google Scholar
  • 27 Valente EM, Marsh SE, Castori M. et al. Distinguishing the four genetic causes of Jouberts syndrome-related disorders. Ann Neurol 2005; 57 (04) 513-519
    Search in Google Scholar
  • 28 Valente EM, Brancati F, Silhavy JL. et al; International JSRD Study Group. AHI1 gene mutations cause specific forms of Joubert syndrome-related disorders. Ann Neurol 2006; 59 (03) 527-534
    Search in Google Scholar
  • 29 Valente EM, Logan CV, Mougou-Zerelli S. et al. Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. Nat Genet 2010; 42 (07) 619-625
    Search in Google Scholar
  • 30 Pizzino G, Irrera N, Galfo F. et al. Effects of the antagomiRs 15b and 200b on the altered healing pattern of diabetic mice. Br J Pharmacol 2018; 175 (04) 644-655
    Search in Google Scholar
  • 31 Salpietro V, Malintan NT, Llano-Rivas I. et al; Deciphering Developmental Disorders Study, SYNAPS Study Group. Mutations in the neuronal vesicular SNARE VAMP2 affect synaptic membrane fusion and impair human neurodevelopment. Am J Hum Genet 2019; 104 (04) 721-730
    Search in Google Scholar
  • 32 Ghosh SG, Becker K, Huang H. et al. Biallelic mutations in ADPRHL2, encoding ADP-ribosylhydrolase 3, lead to a degenerative pediatric stress-induced epileptic ataxia syndrome. [published correction appears in Am J Hum Genet. 2018;103(5):826] [published correction appears in Am J Hum Genet. 2021;108(12):2385] Am J Hum Genet 2018; 103 (03) 431-439
    Search in Google Scholar
  • 33 Bruno L, Ceravolo G, Ceravolo MD. et al. Genetic cardiac channelopathies and SIDS. J Biol Regul Homeost Agents 2020; 34 (4, suppl 2): 55-58
    Search in Google Scholar
  • 34 Pavlidou E, Salpietro V, Phadke R. et al. Pontocerebellar hypoplasia type 2D and optic nerve atrophy further expand the spectrum associated with selenoprotein biosynthesis deficiency. Eur J Paediatr Neurol 2016; 20 (03) 483-488
    Search in Google Scholar
  • 35 Chirico V, Lacquaniti A, Salpietro V, Buemi M, Salpietro C, Arrigo T. Central precocious puberty: from physiopathological mechanisms to treatment. J Biol Regul Homeost Agents 2014; 28 (03) 367-375
    Search in Google Scholar
  • 36 Chimenz R, Manti S, Fede C. et al. Primary nocturnal enuresis in children with allergic rhinitis and severe adenotonsillar hypertrophy: a single center pilot study. J Biol Regul Homeost Agents 2015; 29 (2, suppl 1): 73-79
    Search in Google Scholar
  • 37 Tassano E, Accogli A, Pavanello M. et al. Interstitial 9p24.3 deletion involving only DOCK8 and KANK1 genes in two patients with non-overlapping phenotypic traits. Eur J Med Genet 2016; 59 (01) 20-25
    Search in Google Scholar
  • 38 Loddo I, Barbera F, Di Gesaro G. et al. Genetics and cardiovascular disease. J Biol Regul Homeost Agents 2020; 34 (4, suppl 2): 17-22
    Search in Google Scholar
  • 39 Bell S, Rousseau J, Peng H. et al. Mutations in ACTL6B cause neurodevelopmental deficits and epilepsy and lead to loss of dendrites in human neurons. Am J Hum Genet 2019; 104 (05) 815-834
    Search in Google Scholar
  • 40 Salpietro V, Ruggieri M, Sancetta F. et al. New insights on the relationship between pseudotumor cerebri and secondary hyperaldosteronism in children. J Hypertens 2012; 30 (03) 629-630
    Search in Google Scholar
  • 41 Ruggieri M, Polizzi A, Schepis C. et al. Cutis tricolor: a literature review and report of five new cases. Quant Imaging Med Surg 2016; 6 (05) 525-534
    Search in Google Scholar
  • 42 Efthymiou S, Salpietro V, Malintan N. et al; SYNAPS Study Group. Biallelic mutations in neurofascin cause neurodevelopmental impairment and peripheral demyelination. Brain 2019; 142 (10) 2948-2964
    Search in Google Scholar
  • 43 Dias CM, Punetha J, Zheng C. et al. Homozygous missense variants in NTNG2, encoding a presynaptic netrin-G2 adhesion protein, lead to a distinct neurodevelopmental disorder. Am J Hum Genet 2019; 105 (05) 1048-1056
    Search in Google Scholar
  • 44 Salpietro V, Polizzi A, Granata F, Briuglia S, Mankad K, Ruggieri M. Upper respiratory tract infection and torticollis in children: differential diagnosis of Grisel's syndrome. Clin Neuroradiol 2012; 22 (04) 351-353
    Search in Google Scholar
  • 45 Irrera N, Russo M, Pallio G. et al. The role of NLRP3 inflammasome in the pathogenesis of traumatic brain injury. Int J Mol Sci 2020; 21 (17) 6204
    Search in Google Scholar
  • 46 Loddo I, Cutrupi MC, Concolino D. et al. Cardiac defects in RASopathies: a review of genotype- phenotype correlations. J Biol Regul Homeost Agents 2020; 34 (4, suppl 2): 23-30
    Search in Google Scholar
  • 47 Leu C, Stevelink R, Smith AW. et al; Epi25 Consortium. Polygenic burden in focal and generalized epilepsies. [published correction appears in Brain. 2020;143(7):e61] Brain 2019; 142 (11) 3473-3481
    Search in Google Scholar
  • 48 Pavone P, Briuglia S, Falsaperla R. et al. Wide spectrum of congenital anomalies including choanal atresia, malformed extremities, and brain and spinal malformations in a girl with a de novo 5.6-Mb deletion of 13q12.11-13q12.13. Am J Med Genet A 2014; 164A (07) 1734-1743
    Search in Google Scholar
  • 49 Salpietro V, Zollo M, Vandrovcova J. et al; SYNAPS Study Group. The phenotypic and molecular spectrum of PEHO syndrome and PEHO-like disorders. Brain 2017; 140 (08) e49
    Search in Google Scholar
  • 50 Nicita F, Ruggieri M, Polizzi A. et al. Seizures and epilepsy in Sotos syndrome: analysis of 19 Caucasian patients with long-term follow-up. Epilepsia 2012; 53 (06) e102-e105
    Search in Google Scholar
  • 51 Marseglia L, D'Angelo G, Manti S. et al. Sudden cardiac arrest in a child with nemaline myopathy. Ital J Pediatr 2015; 41: 20
    Search in Google Scholar
  • 52 Salpietro V, Manole A, Efthymiou S, Houlden H. A review of copy number variants in inherited neuropathies. Curr Genomics 2018; 19 (06) 412-419
    Search in Google Scholar
  • 53 Accogli A, Iacomino M, Pinto F. et al. Novel AMPD2 mutation in pontocerebellar hypoplasia, dysmorphisms, and teeth abnormalities. Neurol Genet 2017; 3 (05) e179
    Search in Google Scholar
  • 54 Casto C, Dipasquale V, Ceravolo I. et al. Prominent and regressive brain developmental disorders associated with Nance-Horan syndrome. Brain Sci 2021; 11 (09) 1150
    Search in Google Scholar
  • 55 Piard J, Umanah GKE, Harms FL. et al. A homozygous ATAD1 mutation impairs postsynaptic AMPA receptor trafficking and causes a lethal encephalopathy. Brain 2018; 141 (03) 651-661
    Search in Google Scholar
  • 56 Chelban V, Wilson MP, Warman Chardon J. et al; Care4Rare Canada Consortium and the SYNaPS Study Group. PDXK mutations cause polyneuropathy responsive to pyridoxal 5′-phosphate supplementation. Ann Neurol 2019; 86 (02) 225-240
    Search in Google Scholar
  • 57 Cuppari C, Amatruda M, Ceravolo G. et al. Myocarditis in children - from infection to autoimmunity. J Biol Regul Homeost Agents 2020; 34 (4, suppl 2): 37-41
    Search in Google Scholar
  • 58 Salpietro V, Efthymiou S, Manole A. et al. A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function. Hum Mutat 2018; 39 (02) 187-192
    Search in Google Scholar
  • 59 Granata F, Morabito R, Mormina E. et al. 3T double inversion recovery magnetic resonance imaging: diagnostic advantages in the evaluation of cortical development anomalies. Eur J Radiol 2016; 85 (05) 906-914
    Search in Google Scholar
  • 60 Steel D, Salpietro V, Phadke R. et al. Whole exome sequencing reveals a MLL de novo mutation associated with mild developmental delay and without 'hairy elbows': expanding the phenotype of Wiedemann-Steiner syndrome. J Genet 2015; 94 (04) 755-758
    Search in Google Scholar
  • 61 Nicita F, Di Biasi C, Sollaku S. et al. Evaluation of the basal ganglia in neurofibromatosis type 1. Childs Nerv Syst 2014; 30 (02) 319-325
    Search in Google Scholar
  • 62 Riva A, Gambadauro A, Dipasquale V. et al. Biallelic variants in KIF17 associated with microphthalmia and coloboma spectrum. Int J Mol Sci 2021; 22 (09) 4471
    Search in Google Scholar
  • 63 Sestito S, Roppa K, Parisi F. et al. The heart in Anderson-Fabry disease. J Biol Regul Homeost Agents 2020; 34 (4, suppl 2): 63-69
    Search in Google Scholar
  • 64 Pedullà M, Miraglia Del Giudice M, Fierro V. et al. Atopy as a risk factor for thyroid autoimmunity in children. J Biol Regul Homeost Agents 2012; 26 (1, suppl): S9-S14
    Search in Google Scholar
  • 65 Chimenz R, Chirico V, Cuppari C. et al. Fabry disease and kidney involvement: starting from childhood to understand the future. Pediatr Nephrol 2022; 37 (01) 95-103
    Search in Google Scholar
  • 66 Gramaglia SMC, Cuppari C, Salpietro C. et al. Congenital heart disease in Down syndrome. J Biol Regul Homeost Agents 2020; 34 (4, suppl 2): 31-35
    Search in Google Scholar
  • 67 Salpietro V, Phadke R, Saggar A. et al. Zellweger syndrome and secondary mitochondrial myopathy. Eur J Pediatr 2015; 174 (04) 557-563
    Search in Google Scholar
  • 68 Nascimben F, Peri FM, Impellizzeri P. et al. Role of oxidative stress in the pathogenesis of congenital cardiopathies. J Biol Regul Homeost Agents 2020; 34 (4, suppl 2): 85-90
    Search in Google Scholar
  • 69 Briguglio M, Pinelli L, Giordano L. et al; CBCD Study Group. Pontine tegmental cap dysplasia: developmental and cognitive outcome in three adolescent patients. Orphanet J Rare Dis 2011; 6: 36
    Search in Google Scholar