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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Joubert syndrome (JS) is a primarily autosomal recessive condition characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability with a distinctive mid-hindbrain malformation (the "molar tooth sign"). Variable features include retinal dystrophy, cystic kidney disease, liver fibrosis and polydactyly. Recently, substantial progress has been made in our understanding of the genetic basis of JS, including identification of seven causal genes (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67/MKS3, ARL13B and CC2D2A). Despite this progress, the known genes account for <50% of cases and few strong genotype-phenotype correlations exist in JS; however, genetic testing can be prioritized based on clinical features. While all seven JS genes have been implicated in the function of the primary cilium/basal body organelle (PC/BB), little is known about how the PC/BB is required for brain, kidney, retina and liver development/function, nor how disruption of PC/BB function leads to diseases of these organs. Recent work on the function of the PC/BB indicates that the organelle is required for multiple signaling pathways including sonic hedgehog, WNT and platelet derived growth factor. Due to shared clinical features and underlying molecular pathophysiology, JS is included in the rapidly expanding group of disorders called ciliopathies. The ciliopathies are emerging as models for more complex diseases, where sequence variants in multiple genes contribute to the phenotype expressed in any given patient.
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PMID:Joubert syndrome: insights into brain development, cilium biology, and complex disease. 1977 11

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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PMID:[Joubert syndrome and related disorders]. 2302 37

Duplications of human chromosome 2q13 have been reported in patients with neurodevelopmental disorder including autism spectrum disorder. Nephronophthisis-1 (NPHP1) was identified as a causative gene in the minimal deletion on chromosome 2q13 for familial juvenile type 1 nephronophthisis and Joubert syndrome, an autosomal recessive neurodevelopmental disorder characterized by a cerebellar and brain stem malformation, hypotonia, developmental delay, ataxia, and sometimes associated with cognitive impairment. NPHP1 encodes a ciliary protein, nephrocystin-1, which is expressed in the brain, yet its function in the brain remains largely unknown. In this study, we generated bacterial artificial chromosome-based transgenic mice, called 2q13 dup, that recapitulate human chromosome 2q13 duplication and contain one extra copy of the Nphp1 transgene. To analyze any behavioral alterations in 2q13 dup mice, we conducted a battery of behavioral tests. Although 2q13 dup mice show no significant differences in social behavior, they show deficits in spontaneous alternation behavior and fear memory. We also carried out magnetic resonance imaging to confirm whether copy number gain in this locus affects the neuroanatomy. There was a trend toward a decrease in the cerebellar paraflocculus of 2q13 dup mice. This is the first report of a genetic mouse model for human 2q13 duplication.
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PMID:Behavioral and neuroanatomical analyses in a genetic mouse model of 2q13 duplication. 2837 Aug 17

The police brought a 65-year-old female patient to the EADU after being found 'roaming the streets' in an apparent state of confusion. This was her third admission under the same circumstances during the last 3 years. Neurological examination revealed (1) cognitive impairment, (2) oculomotor apraxia, (3) abnormal cancellation of vestibular ocular reflex, (4) mild ataxia and (5) mild hypotonia. Renal function was abnormal and liver function was normal. No retinal disturbance was found. The head CT on admission was normal for stroke and the lumbar puncture was negative for encephalitis. Her brain MRI showed 'molar tooth sign', suggestive of Joubert syndrome, which was confirmed by genetic testing showing anomalous NPHP1 gene.
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PMID:An elusive ciliopathy: Joubert syndrome. 2866 57


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