TSEN54 Gene-Related Pontocerebellar-Hypoplasia and Role of Prenatal MR Imaging: Besides the Common Posterior Fossa Cystic Malformations

Tortora, Mario; Spaccini, Luigina; Lanna, M.; Zambon, Marta; Izzo, Giana; Parazzini, Cecilia; Righini, Andrea

doi:10.1007/s12311-022-01457-6

Cited by 2 publications

(5 citation statements)

References 11 publications

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“…reported. [7][8][9][10][11][12][13] This is most probably related to the particularities of cerebellar embryology and the natural history of PCH. The cerebellum undergoes protracted development extending from the early embryonic period through the first postnatal years.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, we have identified MRI parameters associated with classic PCH and shown that pons (APDP) measurement significantly correlates with clinical outcome, lower measurements being associated with a worse outcome. So far, only single cases or very short series of prenatal PCH has been reported 7–13 . This is most probably related to the particularities of cerebellar embryology and the natural history of PCH.…”

Section: Discussionmentioning

confidence: 99%

“…Although PCH is mainly of prenatal onset, its prenatal identification has only rarely been reported in single cases or very short case series. [7][8][9][10][11][12][13] The contribution of fetal MRI to the prenatal diagnosis of PCH has yet not been assessed.…”

Section: Introductionmentioning

confidence: 99%

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Prenatal diagnosis of pontocerebellar hypoplasia with postnatal follow‐up

Jaillard,

Valence,

Vande Perre

et al. 2024

Prenatal Diagnosis

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ObjectiveTo describe the MR features enabling prenatal diagnosis of pontocerebellar hypoplasia (PCH).MethodThis was a retrospective single monocentre study. The inclusion criteria were decreased cerebellar biometry on dedicated neurosonography and available fetal Magnetic Resonance Imaging (MRI) with PCH diagnosis later confirmed either genetically or clinically on post‐natal MRI or by autopsy. The exclusion criteria were non‐available MRI and sonographic features suggestive of a known genetic or other pathologic diagnosis. The collected data were biometric or morphological imaging parameters, clinical outcome, termination of pregnancy (TOP), pathological findings and genetic analysis (karyotyping, chromosomal microarray, DNA sequencing targeted or exome). PCH was classified as classic, non‐classic, chromosomal, or unknown type.ResultsForty‐two fetuses were diagnosed with PCH, of which 27 were referred for decreased transverse cerebellar diameter at screening ultrasound. Neurosonography and fetal MRI were performed at a mean gestational age of 29 + 4 and 31 + 0 weeks, respectively. Termination of pregnancy occurred. Pregnancy was terminated in 24 cases. Neuropathological examination confirmed the diagnosis in 24 cases and genetic testing identified abnormalities in 29 cases (28 families, 14 chromosomal anomaly). Classic PCH is associated with pontine atrophy and small MR measurements decreasing with advancing gestation.ConclusionThis is the first large series of prenatally diagnosed PCHs. Our study shows the essential contribution of fetal MRI to the prenatal diagnosis of PCH. Classic PCHs are particularly severe and are associated with certain MR features.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prenatal diagnosis of pontocerebellar hypoplasia with postnatal follow‐up

Jaillard,

Valence,

Vande Perre

et al. 2024

Prenatal Diagnosis

View full text Add to dashboard Cite

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“…PCH5 is associated with similar levels of cortical involvement compared to PCH4, though more extensive vermis involvement is prominent, which is also observed in MRI results. This type is also associated with the loss of dentate nuclei in the cerebellum [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

“…PCH4 cases either display compound heterozygous genotypes at the same site or result from splice site mutations. In PCH5 cases, both compound heterozygous genotypes at this site and splice site mutations are observed [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review

Ghasemi,

Tehrani Fateh,

Moeinafshar

et al. 2024

BMC Med Genomics

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Background Pontocerebellar hypoplasia is an umbrella term describing a heterogeneous group of prenatal neurodegenerative disorders mostly affecting the pons and cerebellum, with 17 types associated with 25 genes. However, some types of PCH lack sufficient information, which highlights the importance of investigating and introducing more cases to further elucidate the clinical, radiological, and biochemical features of these disorders. The aim of this study is to provide an in-depth review of PCH and to identify disease genes and their inheritance patterns in 12 distinct Iranian families with clinically confirmed PCH. Methods Cases included in this study were selected based on their phenotypic and genetic information available at the Center for Comprehensive Genetic Services. Whole-exome sequencing (WES) was used to discover the underlying genetic etiology of participants' problems, and Sanger sequencing was utilized to confirm any suspected alterations. We also conducted a comprehensive molecular literature review to outline the genetic features of the various subtypes of PCH. Results This study classified and described the underlying etiology of PCH into three categories based on the genes involved. Twelve patients also were included, eleven of whom were from consanguineous parents. Ten different variations in 8 genes were found, all of which related to different types of PCH. Six novel variations were reported, including SEPSECS, TSEN2, TSEN54, AMPD2, TOE1, and CLP1. Almost all patients presented with developmental delay, hypotonia, seizure, and microcephaly being common features. Strabismus and elevation in lactate levels in MR spectroscopy were novel phenotypes for the first time in PCH types 7 and 9. Conclusions This study merges previously documented phenotypes and genotypes with unique novel ones. Due to the diversity in PCH, we provided guidance for detecting and diagnosing these heterogeneous groups of disorders. Moreover, since certain critical conditions, such as spinal muscular atrophy, can be a differential diagnosis, providing cases with novel variations and clinical findings could further expand the genetic and clinical spectrum of these diseases and help in better diagnosis. Therefore, six novel genetic variants and novel clinical and paraclinical findings have been reported for the first time. Further studies are needed to elucidate the underlying mechanisms and potential therapeutic targets for PCH.

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TSEN54 Gene-Related Pontocerebellar-Hypoplasia and Role of Prenatal MR Imaging: Besides the Common Posterior Fossa Cystic Malformations

Cited by 2 publications

References 11 publications

Prenatal diagnosis of pontocerebellar hypoplasia with postnatal follow‐up

Prenatal diagnosis of pontocerebellar hypoplasia with postnatal follow‐up

Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review

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