A Novel CCND2 Mutation in a Previously Reported Case of Megalencephaly and Perisylvian Polymicrogyria with Postaxial Polydactyly and Hydrocephalus

Maini, Ilenia; Farnetti, Enrico; Caraffi, Stefano Giuseppe; Ivanovski, Ivan; Bernardi, Margherita Lucia De; Gelmini, Chiara; Pollazzon, Marzia; Rosato, Simonetta; Laurie, Steve; Matalonga, Leslie; Baldo, Chiara; Garavelli, Livia

doi:10.1055/s-0038-1641722

Cited by 8 publications

(6 citation statements)

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“…The Thr280 residue was previously found to be affected in individuals with PMG (McDermott et al, ; Mirzaa et al, ). Moreover, a 10‐year‐old female individual was previously reported to carry the same p.(Thr280Ile) variant detected in the individual herein described, and presented with a largely overlapping phenotype characterized by severe developmental delay and drug‐resistant epilepsy, generalized MEG, widespread PMG, hydrocephalus requiring surgical intervention, corpus callosum hypoplasia, and postaxial polydactyly (Garavelli et al, ; Maini et al, ). However, the individual herein described did not require shunting for the hydrocephalus, and presented with additional and previously unreported brain findings including skull base abnormalities, hippocampus hypoplasia and malrotation, hypomyelination, and cerebellar anomalies.…”

Section: Discussionsupporting

confidence: 55%

“…Brain MRI abnormalities detected so far in individuals harboring CCND2 variants include hydrocephalus, ventriculomegaly, and PMG mainly in the perisylvian region (Maini et al, ; McDermott et al, ; Mirzaa et al, ). The Thr280 residue was previously found to be affected in individuals with PMG (McDermott et al, ; Mirzaa et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Variants in CCND2 (OMIM 123833) encoding cyclin D2, a downstream mediator of PI3K‐AKT pathway, have been reported in 14 patients with MPPH so far (Maini et al, ; McDermott et al, ; Mirzaa et al, ). Recurrent variants at four different codons (p.Lys270, p.Thr280, p.Pro281 and p.Val284) have been reported (Maini et al, ; McDermott et al, ; Mirzaa et al, ). Neuroimaging of MPPH due to CCND2 variants includes progressive and striking MEG and polymicrogyria (PMG) without vascular anomalies (Mirzaa, Riviere, & Dobyns, ).…”

Section: Introductionmentioning

confidence: 99%

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Severe presentation and complex brain malformations in an individual carrying a CCND2 variant

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Parrini

et al. 2019

Molec Gen & Gen Med

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Background Megalencephaly‐polymicrogyria‐polydactyly‐hydrocephalus (MPPH) is a developmental brain disorder characterized by megalencephaly and bilateral perisylvian polymicrogyria due to defects in genes of the PI3K‐AKT pathway. Only a few patients with CCND2 mutations have been reported to date. Methods We describe an individual harboring a de novo variant in CCND2 undergoing neuroradiological evaluation including diffusion tensor imaging (DTI). Results The individual presented with a severe brain malformation extending to both brainstem and cerebellum with hypomyelination not previously reported in CCND2‐related disorder. Severe hypoplasia and white matter disorganization were confirmed by DTI. Conclusion This report expands the phenotypic spectrum of the disorder due to CCND2 variants.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Severe presentation and complex brain malformations in an individual carrying a CCND2 variant

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Ugga

Parrini

et al. 2019

Molec Gen & Gen Med

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“…The (43%) fully analyzed families have been solved (Ivanovski et al, 2020;Maini et al, 2018Maini et al, , 2021Saredi et al, 2019;Urreizti et al, 2020).…”

Section: Impact On Rare Disease Diagnosismentioning

confidence: 99%

The RD‐Connect Genome‐Phenome Analysis Platform: Accelerating diagnosis, research, and gene discovery for rare diseases

et al. 2022

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Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is processed through a standardized pipeline. After an optional embargo period, the data are shared with other platform users, with the objective that similar cases in the system and queries from peers may help diagnose the case.Additionally, the platform enables bidirectional discovery of similar cases in other databases from the Matchmaker Exchange network. To facilitate genome-phenome

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“…Tumor pathology returned as large cell/anaplastic medulloblastoma (WHO Grade IV, Group 3/4) with no Myc amplification detected. Further molecular genetic testing on the tumor tissue showed the known variant in CCND2, specifically a missense mutation in a mutational hotspot shown to increase Rb phosphorylation leading to increased proliferation in vitro (CCND2 c.839C > T (p.T280I)) (Eisfeld et al, 2017;Maini et al, 2018). risk of malignancy.…”

Section: Casementioning

confidence: 99%

Medulloblastoma in the setting of megalencephaly polymicrogyria polydactyly hydrocephalus

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Karsten

Olson

et al. 2021

American J of Med Genetics Pt A

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A Novel CCND2 Mutation in a Previously Reported Case of Megalencephaly and Perisylvian Polymicrogyria with Postaxial Polydactyly and Hydrocephalus

Cited by 8 publications

References 6 publications

Severe presentation and complex brain malformations in an individual carrying a CCND2 variant

Severe presentation and complex brain malformations in an individual carrying a CCND2 variant

The RD‐Connect Genome‐Phenome Analysis Platform: Accelerating diagnosis, research, and gene discovery for rare diseases

Medulloblastoma in the setting of megalencephaly polymicrogyria polydactyly hydrocephalus

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