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: 0.54). 01/2012; 46(4):379-383. DOI: 10.5114/ninp.2012.30457
Source: PubMed

ABSTRACT 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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    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.
    Revista Paulista de Pediatria 06/2009; 27(2). DOI:10.1590/S0103-05822009000200016
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    ABSTRACT: Joubert syndrome is an autosomal recessive disorder characterized by a variable combination of mental retardation, cerebellar ataxia, episodic hyperpnea, eye movement abnormalities, generalized hypotonia, and the molar-tooth sign visible on brain imaging. The number of reported cases has been escalating scalating all over the world since the description of the syndrome by the late French neurologist Marie Joubert in 1969, but the syndrome remains under-diagnosed; failure to recognize its core features and unfamiliarity with the brain imaging findings are the main culprits. In 2011, we reported on three Iraqi children who had been diagnosed with Joubert syndrome and it was the first-ever published case series from Iraq. Two of them were already misdiagnosed as ataxic cerebral palsy and hereditary spinocerebellar ataxia. The third child presented with delayed milestones. During the past 2 years, we have been regularly following-up those children on an outpatient basis, every 6 months. The first child’s epilepsy has been well-controlled and no breakthrough seizures have been reported while the second child’s diffuse icthyosis has been more or less the same; their moderate intellectual disability and cerebellar ataxia have been plateaued. The third child’s Leber’s congenital amaurosis and poor vision hasn’t progressed further and he is unable to sit or stand without major assistance; his age is 2 years and 7 months. None of the children has a family history of the same illness. No renal or hepatic involvements have been found during the past 2 years of follow-up.
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    ABSTRACT: Nephronophthisis (NPHP), which affects multiple organs, is a hereditary cystic kidney disease (CKD), characterized by interstitial fibrosis and numerous fluid-filled cysts in the kidneys. It is caused by mutations in NPHP genes, which encode for ciliary proteins known as nephrocystins. The disorder affects many people across the world and leads to end-stage renal disease. The aim of this study was to determine if the genetic background of the nonmutant female Piebald-Virol-Glaxo (PVG/Seac(-/-)) rat influences phenotypic inheritance of NPHP from mutant male Lewis polycystic kidney rats. Mating experiments were performed between mutant Lewis polycystic kidney male rats with CKD and nonmutant PVG and Wistar Kyoto female rats without cystic kidney disease to raise second filial and backcross 1 progeny, respectively. Rats that developed cystic kidneys were identified. Systolic blood pressure was determined in each rat at 12 weeks of age using the tail and cuff method. After euthanasia, blood samples were collected and chemistry was determined. Histological examination of the kidneys, pancreas, and liver of rats with and without cystic kidney disease was performed. It was established that the genetic background of nonmutant female PVG rats did not influence the phenotypic inheritance of the CKD from mutant male Lewis polycystic kidney rats. The disease arose as a result of a recessive mutation in a single gene (second filial generation, CKD = 13, non-CKD = 39, χ (2) = 0.00, P ≥ 0.97; backcross 1 generation, CKD = 67, non-CKD = 72, χ (2) = 0.18, P > 0.05) and inherited as NPHP. The rats with CKD developed larger fluid-filled cystic kidneys, higher systolic blood pressure, and anemia, but there were no extrarenal cysts and disease did not lead to early pup mortality. The genetic background of the nonmutant PVG rats does not influence the genetic and phenotypic inheritance of CKD from mutant Lewis polycystic kidney rats. A single recessive mutation incapacitated the gene, which relaxed its functional constraints, and led to formation of multiple cysts in the kidneys of the homozygous mutant rats.
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