The syndrome of autosornal recessive pontocerebellar hypoplasia, microcephaly, and extrapyramidal dyskinesia (pontocerebellar hypoplasia type 2)

Barth, P. G.; Blennow, Gösta; Lenard, H. G.; Begeer, J. H.; Kley, Joao; Hanefeld, F.; Peters, A. C. B.; Valk, Jacob

doi:10.1212/wnl.45.2.311

Cited by 74 publications

(42 citation statements)

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“…9 Although milder, the clinical findings in PCH2 are similar to what is reported in PCH4 and PCH5. 10 Early postnatal lethality due to hypoventilation, as observed in the firstborn of the PCH5 family, is also commonly observed in PCH4. 1 Thus, our molecular genetic findings and the phenotype in PCH5 are similar to that of PCH4.…”

Section: Resultsmentioning

confidence: 99%

TSEN54 mutations cause pontocerebellar hypoplasia type 5

et al. 2011

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Pontocerebellar hypoplasia (PCH) is a group of autosomal recessive neurodegenerative disorders characterized by prenatal onset of stunted brain growth and progressive atrophy predominantly affecting cerebellum, pons and olivary nuclei, and to a lesser extent also the cerebral cortex. Six subtypes (PCH1-6) were described and genes for four types (PCH1, 2, 4 and 6) were identified. Mutations in the tRNA splicing endonuclease subunit (TSEN) genes 54, 2 and 34 are found in PCH2 and PCH4. One family with severe prenatal onset of PCH has been the only representative of PCH5 published so far, and the molecular genetic status of PCH5 has not been ascertained until now. We screened the previously reported PCH5 family for mutations in the TSEN54 gene. The PCH5 patient was found to be the result of compound heterozygosity for the common TSEN54 mutation (p.A307S) plus a novel splice site mutation. The mutations associated with PCH5 are similar to what has been reported in PCH4. Thus, PCH5, PCH4 and PCH2 represent a spectrum of clinical manifestations caused by different mutations in the TSEN genes. We, therefore, propose to classify PCH2, PCH4 and PCH5 as TSEN mutation spectrum disorders.

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Section: Resultsmentioning

confidence: 99%

TSEN54 mutations cause pontocerebellar hypoplasia type 5

et al. 2011

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“…Subsequent publications have confirmed the distinction between the two main types [Barth et al, 1995;Uhl et al, 1998;Muntoni et al, 1999;Coppola et al, 2000;Dilber et al, 2002;Grosso et al, 2002]. The genetic basis of both types is not yet elucidated.…”

Section: Pontocerebellar Hypoplasiasmentioning

confidence: 93%

Cerebellum—small brain but large confusion: A review of selected cerebellar malformations and disruptions

Boltshauser

2004

American J of Med Genetics Pt A

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Defining and classifying congenital disorders of the cerebellum can be difficult and confusing. One reason is that some abnormalities called "malformations" are not truly (primary) developmental malformations. This applies to Chiari I "malformations" as well as to Chiari II "malformations." The latter results mainly from a prenatal cerebrospinal fluid (CSF) leak. Also disruptive cerebellar lesions are not uncommon, examples being the "vanishing cerebellum" in myelomeningocele, cerebellar lesions in very low birth weight prematurely born infants, unilateral cerebellar hypoplasia/aplasia, and probably some instances of cerebellar agenesis (CA). The cerebellar hypoplasias consist of a heterogeneous group of inherited and prenatally acquired conditions. The concept of pontocerebellar hypoplasias will need to be expanded beyond the two main types (PCH-1 and PCH-2), and demonstrate that a classification system of cerebellar malformations cannot be based on neuroimaging criteria only. Additional studies are expected to show that this also applies to the molar tooth sign, which was initially described in Joubert syndrome (JS). The JS is the prototype of midhindbrain malformation, but its delineation is still unsolved. JS may well be an overdiagnosed entity; many cases likely not having JS are on record. Rhombencephalosynapsis (RS) has been increasingly diagnosed with the advent of neuroimaging. No familial cases have been observed. Although many affected individuals have variable impairments, RS can be found in children with normal cognitive function. In this review, some of the cerebellar anomalies are briefly discussed.

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“…15,16 None of our cases had a posterior encephalocele, and the 1 case with an encephalocele had a form of holoprosencephaly. Other possible considerations for the hindbrain findings in our series included pontocerebellar or pontoneocerebellar hypoplasia, [17][18][19] the Chiari III malformation, 20 and the Dandy-Walker spectrum. However, there were no specific clinical or morphologic findings in our cases that would be consistent with any of these other conditions.…”

Section: Discussionmentioning

confidence: 99%

Magnetic Resonance Imaging of the Kinked Fetal Brain Stem

Stroustrup

Levine

Barnes

et al. 2005

Journal of Ultrasound in Medicine

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Objective. Magnetic resonance imaging (MRI) allows visualization of the fetal brain stem in a manner not previously possible. A "kinked" brain stem is a sign of severe neurodysgenesis. The purpose of this series was to describe cases of a kinked brain stem detected on prenatal MRI and to discuss the possible genetic and syndromic etiologies. Methods. Seven cases of a kinked brain stem on fetal MRI (gestational age range, 18-34 weeks) were reviewed and correlated with other clinical, genetic, imaging, and autopsy findings. Results. In all cases, there was associated cerebellar hypogenesis. Additional findings were ventriculomegaly (4 cases), cerebral hypogenesis (3 cases), microcephaly (4 cases), schizencephaly (1 case), cephalocele (1 case), hypogenesis of the corpus callosum (1 case), and hydrocephalus (1 case). In 2 cases, prenatal sonography misidentified the kinked brain stem as the cerebellum. Conclusions. A kinked brain stem is an indicator of severe neurodysgenesis arising early in gestation. Magnetic resonance imaging provides the necessary resolution to detect this sign and delineate any associated anomalies in utero to assist with further genetic evaluation, management, and counseling. Key words: brain stem; midbrain; prenatal diagnosis; ventriculomegaly. isualization of the posterior fossa is routine on fetal sonography. However, the brain stem is difficult to fully assess. Magnetic resonance imaging (MRI) allows visualization of the brain stem in a manner not previously possible in utero. We describe 7 cases of a "kinked" brain stem detected on prenatal MRI and discuss the possible genetic and syndromic etiologies. Materials and MethodsReview of the prenatal MRI database from August 1998 through August 2005 from Beth Israel Deaconess Medical Center revealed 7 cases with the finding of a kinked brain stem. All MRI examinations had been performed as part of an Institutional Review Board-approved study, including written informed consent, to compare prenatal sonography with MRI for imaging of the fetal central nervous system (CNS). The medical records were reviewed along with postnatal clinical, imaging, and autopsy data.

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The syndrome of autosornal recessive pontocerebellar hypoplasia, microcephaly, and extrapyramidal dyskinesia (pontocerebellar hypoplasia type 2)

Cited by 74 publications

References 6 publications

TSEN54 mutations cause pontocerebellar hypoplasia type 5

TSEN54 mutations cause pontocerebellar hypoplasia type 5

Cerebellum—small brain but large confusion: A review of selected cerebellar malformations and disruptions

Magnetic Resonance Imaging of the Kinked Fetal Brain Stem

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