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

Joubert syndrome is an autosomal recessive disorder characterized by hypotonia, ataxia, developmental delay, and a distinctive hindbrain malformation involving the cerebellum and brain stem, visualized radiographically on magnetic resonance imaging (MRI) as the "molar tooth sign." In postmortem brains from subjects with Joubert syndrome, there is an apparent absence of decussation of both corticospinal and superior cerebellar tracts, although the functional significance has not been elucidated. We sought to explore the cerebral and cerebellar activation pattern elicited by finger tapping in an adolescent with Joubert syndrome and in a normal control subject using functional MRI. In contrast to the typical highly lateralized activation seen in our control subject, the subject with Joubert syndrome demonstrated striking bilateral activation of the sensorimotor and cerebellar cortex. Although our functional MRI data do not indicate a clear absence of decussation, the abnormal activation pattern observed suggests altered brain functional organization in relation to anatomic differences. Malformation of the hindbrain could result in recruitment of alternative pathways, similar to what has been observed following ischemic injury to the developing or mature central nervous system.
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PMID:Cerebral and cerebellar motor activation abnormalities in a subject with Joubert syndrome: functional magnetic resonance imaging (MRI) study. 1511 82

Joubert syndrome is a rare genetic neurologic disorder associated with hypoplasia or absence of the cerebellar vermis. The classic form is characterized by ataxia, hypotonia, eye movement abnormalities, developmental delay, and abnormal breathing patterns. In contrast, other patients have the additional feature of kidney cysts. This population could represent a distinct form of Joubert syndrome. One case of Joubert syndrome with subcortical neuroepithelial cysts was recently described. We report a new case of Joubert syndrome with overlapping features, including diffuse progressive central nervous system neuroepithelial cysts and kidney cysts. Our data suggest that neuroepithelial cysts occur in conjunction with Joubert syndrome associated with kidney cysts.
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PMID:Neuroepithelial cysts in a patient with Joubert syndrome plus renal cysts. 1511 86

Joubert syndrome (JS) is an autosomal recessive multisystem disease characterized by cerebellar vermis hypoplasia with prominent superior cerebellar peduncles (the "molar tooth sign" [MTS] on axial magnetic resonance imaging), mental retardation, hypotonia, irregular breathing pattern, and eye-movement abnormalities. Some individuals with JS have retinal dystrophy and/or progressive renal failure characterized by nephronophthisis (NPHP). Thus far, no mutations in the known NPHP genes, particularly the homozygous deletion of NPHP1 at 2q13, have been identified in subjects with JS. A cohort of 25 subjects with JS and either renal and/or retinal complications and 2 subjects with only juvenile NPHP were screened for mutations in the NPHP1 gene by standard methods. Two siblings affected with a mild form of JS were found to have a homozygous deletion of the NPHP1 gene identical, by mapping, to that in subjects with NPHP alone. A control subject with NPHP and with a homozygous NPHP1 deletion was also identified, retrospectively, as having a mild MTS and borderline intelligence. The NPHP1 deletion represents the first molecular defect associated with JS in a subset of mildly affected subjects. Cerebellar malformations consistent with the MTS may be relatively common in patients with juvenile NPHP without classic symptoms of JS.
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PMID:The NPHP1 gene deletion associated with juvenile nephronophthisis is present in a subset of individuals with Joubert syndrome. 1513 99

Joubert syndrome (JS) is an autosomal-recessive disorder, characterized by hypotonia, ataxia, global developmental delay and molar tooth sign on magnetic resonance imaging. A variety of other abnormalities have been described in children with JS, including abnormal breathing, abnormal eye movements, a characteristic facial appearance, delayed language, hypersensitivity to noise, autism, ocular and oculomotor abnormalities, meningoencephaloceles, microcephaly, low-set ears, polydactyly, retinal dysplasia, kidney abnormalities (renal cysts), soft tissue tumor of the tongue, liver disease and duodenal atresia. Even within siblings the phenotype may vary, making it difficult to establish the exact clinical diagnostic boundaries of JS. We review the clinical characteristics of seven cases that fulfill the criteria of JS.
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PMID:Joubert syndrome: review and report of seven new cases. 1527 93

Joubert syndrome (JS) is an autosomal recessive disorder marked by agenesis of the cerebellar vermis, ataxia, hypotonia, oculomotor apraxia, neonatal breathing abnormalities, and mental retardation. Despite the fact that this condition was described >30 years ago, the molecular basis has remained poorly understood. Here, we identify two frameshift mutations and one missense mutation in the AHI1 gene in three consanguineous families with JS, some with cortical polymicrogyria. AHI1, encoding the Jouberin protein, is an alternatively spliced signaling molecule that contains seven Trp-Asp (WD) repeats, an SH3 domain, and numerous SH3-binding sites. The gene is expressed strongly in embryonic hindbrain and forebrain, and our data suggest that AHI1 is required for both cerebellar and cortical development in humans. The recently described mutations in NPHP1, encoding a protein containing an SH3 domain, in a subset of patients with JS plus nephronophthisis, suggest a shared pathway.
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PMID:Mutations in the AHI1 gene, encoding jouberin, cause Joubert syndrome with cortical polymicrogyria. 1546 82

Joubert syndrome is a rare disorder, characterized by hypoplasia, or aplasia of the cerebellar vermis, hypotonia, ataxia, and psychomotor retardation. The molecular basis underlying the disease is still unknown. There are various syndromes, which are associated with malignancies. Previously known associations between Joubert syndrome and tumors, are benign soft tissue tumors of the tongue and laryngeal lymphangioma. This report describes a 17-year-old boy known with Joubert syndrome, who was diagnosed with Burkitt lymphoma. The boy received chemotherapy, which successfully induced complete remission.
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PMID:Burkitt lymphoma in a child with Joubert syndrome. 1592 61

We present a so far unrecognized X-linked mental retardation syndrome with features overlapping with Joubert syndrome (JBS). Two brothers showed hypotonia, mental retardation, ocular abnormalities with impaired vision and colobomas and a breathing pattern compatible with JBS. Neuroimaging revealed cerebellar vermis hypoplasia and ventriculomegaly. A tentative diagnosis of JBS was made, and autosomal recessive inheritance considered most likely. In a subsequent pregnancy that occurred after artificial donor insemination, ultrasound in the 22nd week revealed a Dandy-Walker malformation and hydrocephaly. At autopsy at 34 weeks of gestation, the male infant showed cerebellar vermis aplasia and abnormalities of the brainstem and cerebral cortex. He was considered to have the same disorder as his two half-brothers. This renders the pedigree highly suggestive of X-linked inheritance. The clinical symptoms of this syndrome resemble JBS. However, the absence of the molar tooth sign and the X-linked inheritance do not support JBS. We propose the name X-linked cerebral-cerebellar-coloboma syndrome to distinguish the two disorders. Differentiation of the two disorders is especially important in genetic counseling, where artificial donor insemination may be considered as a means of reducing the recurrence risk, or when female relatives of the patient are concerned.
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PMID:Cerebral, cerebellar, and colobomatous anomalies in three related males: Sex-linked inheritance in a newly recognized syndrome with features overlapping with Joubert syndrome. 1588 74

Joubert syndrome is a genetically heterogeneous disorder. The diagnostic criteria include episodic hyperventilation, abnormal eye movements, psychomotor retardation, hypotonia, ataxia, and the characteristic neuro-imaging findings (molar-tooth sign). Many of these clinical features have been observed in new-borns with mitochondrial disorders as well. Congenital brain malformations, including cerebellar hypoplasia, have been described in pyruvate dehydrogenase deficiency. Malformations of the vermis and the cerebellar peduncles, with the lack of axonal decussations, however, are characteristic for Joubert syndrome but unique in patients with mitochondrial disorders. Here, we describe a child with Joubert syndrome presenting with primary lactic acidemia, decreased pyruvate oxidation rates, decreased ATP production, and a mildly decreased pyruvate dehydrogenase complex activity measured in a fresh muscle biopsy. Sequence analysis of the PDHc E1 alpha gene and the PDHX genes revealed no mutations. The patient received continuous feeding through a feeding tube for two years and showed a significant clinical improvement with a complete resolution of the chronic lactic acidemia. A second muscle biopsy revealed significantly decreased pyruvate oxidation rates and ATP production, but a normal pyruvate dehydrogenase complex activity. We suggest that the described mitochondrial dysfunction in our patient is secondary to an underlying mutation leading to Joubert syndrome.
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PMID:Mitochondrial dysfunction in a patient with Joubert syndrome. 1594 9

Joubert syndrome (JBTS) is an autosomal recessive multisystem disease characterized by cerebellar vermis aplasia, mental retardation, muscular hypotonia, an irregular breathing pattern in the neonatal period and abnormal eye movements. Some individuals have progressive renal failure characterized by nephronophthisis (NPHP) and/or retinal dystrophy. Homozygous deletions of NPHP1 on chromosome 2q13 have been identified in individuals with NPHP-associated JBTS. Recently, mutations in AHI1 on chromosome 6q23.3 were found in JBTS patients without NPHP. Here, by direct sequencing, we identify novel truncating mutations within AHI1 in affected patients from two families. One patient had the association of JBTS and NPHP with chronic renal failure. This is the first report of AHI1 mutations causing JBTS associated with NPHP, confirming the clinical and genetic heterogeneity of NPHP.
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PMID:Identification of the first AHI1 gene mutations in nephronophthisis-associated Joubert syndrome. 1624 Jan 61

We have identified a group of 13 patients with a homogeneous radiological pattern at MRI consisting of the molar tooth sign (MTS) and superior vermian dysplasia. The patients represent a relatively heterogeneous clinical group with variable severity of developmental delay, ataxia, hypotonia, and apnea. Careful examination of MRI prompted us to split our series of patients into two groups, based on IVth ventricle dilatation. In 4/13 patients the IVth ventricle was judged to be dilated and those patients were less severely affected while most clinically affected patients had a normal IVth ventricle. DNA samples of blood leukocytes from 6/13 consanguineous patients were genotyped using polymorphic markers encompassing the Joubert syndrome loci. We therefore sequenced AHI1 located in 6q23 in two patients who were homozygous at the locus and in four sporadic cases. Only one homozygous nonsense mutation was identified. Clinically, the patient exhibiting the AHI1 mutation was the most severely affected child with a profound encephalopathy, major hypotonia, ataxia, Leber congenital amaurosis, and normal IVth ventricle at the MRI. The present study suggests that the syndrome associating MTS and dysplasia of the superior vermis of the cerebellum is a clinically and genetically heterogeneous entity and that Jouberin (AHI1) mutations account for a marginal fraction of patients.
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PMID:Molar tooth sign and superior vermian dysplasia: a radiological, clinical, and genetic study. 1654 67


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