Joubert syndrome and related disorders

Justyna Paprocka, Child Neurology Department, Medical University of Silesia, ul. Medyków 16, 40-752 Katowice, Poland, phone: +48 32 207 16 00, fax: +48 32 207 16 15, e-mail: .
Neurologia i neurochirurgia polska (Impact Factor: 0.64). 07/2012; 46(4):379-383. DOI: 10.5114/ninp.2012.30457
Source: PubMed


The cerebellum plays a role not only in motor control but also in motor learning and cognition. Joubert syndrome is a rare heterogeneous inherited genetic disorder characterized by ataxia, hypotonia, developmental delay, and at least one of the following features: neonatal respiratory disturbances or abnormal eye movement. The estimated frequency of Joubert syndrome in the United States is around 1 : 100 000. The term Joubert syndrome and related disorders (JSRD) has been recently coined to describe all disorders presenting with molar tooth sign on brain neuroimaging. Joubert syndrome is believed to be a representative of a new group of disorders named ciliopathies. The identification of seven causal genes (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67/MKS3, ARL13B, CC2D2A) has led to substantial progress in the understanding of the genetic basis of Joubert syndrome. The authors focus on clinical presentation of JSRD, differential diagnosis and molecular background.

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    • "The syndrome is characterized by the association of cystic dysplastic kidneys which is identified by abnormal metanephric development with macroscopically large kidneys and prominent cysts, congenital blindness, the molar tooth sign (MTS), and sometimes an encephalocele . However, the existence of Arima syndrome as a separate entity has been questioned [2]. A re-examination of some of the original patients showed histological abnormalities more typical of nephronophthisis, suggesting that all JSRD present the same renal phenotype [3]. "

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    ABSTRACT: Objective: To describe the case of a patient with Joubert syndrome associated with renal impairments. Case description: A 2 month-old patient was admit- ted with hypotonia and hyperpneia. At the physical exam, besides irregular breathing pattern, abnormal eye move- ments and arterial hypertension without abnormalities in cardiac or pulmonary sounds were observed. At the initial clinical and laboratorial investigations, cardiac and pulmo- nary causes were excluded. The diagnostic hypothesis was: neurological illness associated with renal disease. Labo- ratorial analysis showed respiratory alkalosis, metabolic acidosis and hyperkalemia, with normal renal function. In the magnetic resonance, images of neurological alterations were compatible with the "molar tooth sign", frequently associated with Joubert syndrome. Renal investigation was performed and cystic images in renal parenchyma were found. Comments: Cardiac and pulmonary illness are frequently associated with clinical manifestations such as tachypnea and metabolic alterations. Nevertheless, neurological investigation may be necessary, since some diseases that affect the central nervous system may manifest these signs and symptoms. Association between renal alterations and central nervous system malformations are frequent in sev- eral diseases and should be investigated. Joubert syndrome and its associated disorders are characterized by aplasia of the cerebellar vermis, ataxia, abnormal eye movements and irregular breathing pattern with psychomotor and mental delay. The most frequent renal problems associated with the disease are renal cysts and nephronophtisis that can progress to end-stage renal failure.
    Preview · Article · Jun 2009 · Revista Paulista de Pediatria
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    ABSTRACT: The human Abelson helper integration site-1 (AHI1) gene is associated with both neurologic and hematologic disorders; however, it is also located in a chromosomal region linked to metabolic syndrome phenotypes and was identified as a type 2 diabetes mellitus susceptibility gene from a genomewide association study. To further define a possible role in type 2 diabetes mellitus development, AHI1 messenger RNA expression levels were investigated in a range of tissues and found to be highly expressed in skeletal muscle as well as displaying elevated levels in brain regions and gonad tissues. Further analysis in a rodent polygenic animal model of obesity and type 2 diabetes mellitus identified increased Ahi-1 messenger RNA levels in red gastrocnemius muscle from fasted impaired glucose-tolerant and diabetic rodents compared with healthy animals (P < .002). Moreover, elevated gene expression levels were confirmed in skeletal muscle from fasted obese and type 2 diabetes mellitus human subjects (P < .02). RNAi-mediated suppression of Ahi-1 resulted in increased glucose transport in rat L6 myotubes in both the basal and insulin-stimulated states (P < .01). Finally, single nucleotide polymorphism association studies identified 2 novel AHI1 genetic variants linked with fasting blood glucose levels in Mexican American subjects (P < .037). These findings indicate a novel role for AHI1 in skeletal muscle and identify additional genetic links with metabolic syndrome phenotypes suggesting an involvement of AHI1 in the maintenance of glucose homeostasis and type 2 diabetes mellitus progression.
    Full-text · Article · Jul 2010 · Metabolism: clinical and experimental
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