Teaching NeuroImages: A rare case of Jacobsen syndrome with global diffuse hypomyelination of brain

Patel, Himadri; Kumar, Ashutosh; Raymond, Gerald V.; Mainali, Gayatra

doi:10.1212/wnl.0000000000007234

Cited by 6 publications

(2 citation statements)

References 2 publications

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“…MRI abnormalities resembling MLC have been described in Jacobsen syndrome patients already long ago, which led to the speculation that a leukodystrophy gene could be located in this region ( Wardinsky et al, 1990 ; Gutmann, 1991 ). Indeed, deletion of 11q24 including GLIALCAM was later linked to MLC-like white matter abnormalities with diffuse signal abnormality and swelling of the cerebral white matter in several patients ( Yamamoto et al, 2015 ; Patel et al, 2019 ; Wolf and van der Knaap, 2020 ). Importantly, the MRI phenotype in Jacobsen syndrome is remitting (similar to what is seen in remitting MLC; see Figure 5 for an example from the ALC database).…”

Section: Variantsmentioning

confidence: 99%

Megalencephalic leukoencephalopathy with subcortical cysts: a variant update and review of the literature

Passchier,

Bisseling,

Helman

et al. 2024

Front. Genet.

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The leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC) is characterized by infantile-onset macrocephaly and chronic edema of the brain white matter. With delayed onset, patients typically experience motor problems, epilepsy and slow cognitive decline. No treatment is available. Classic MLC is caused by bi-allelic recessive pathogenic variants in MLC1 or GLIALCAM (also called HEPACAM). Heterozygous dominant pathogenic variants in GLIALCAM lead to remitting MLC, where patients show a similar phenotype in early life, followed by normalization of white matter edema and no clinical regression. Rare patients with heterozygous dominant variants in GPRC5B and classic MLC were recently described. In addition, two siblings with bi-allelic recessive variants in AQP4 and remitting MLC have been identified. The last systematic overview of variants linked to MLC dates back to 2006. We provide an updated overview of published and novel variants. We report on genetic variants from 508 patients with MLC as confirmed by MRI diagnosis (258 from our database and 250 extracted from 64 published reports). We describe 151 unique MLC1 variants, 29 GLIALCAM variants, 2 GPRC5B variants and 1 AQP4 variant observed in these MLC patients. We include experiments confirming pathogenicity for some variants, discuss particularly notable variants, and provide an overview of recent scientific and clinical insight in the pathophysiology of MLC.

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Section: Variantsmentioning

confidence: 99%

Megalencephalic leukoencephalopathy with subcortical cysts: a variant update and review of the literature

Passchier,

Bisseling,

Helman

et al. 2024

Front. Genet.

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“…To date, various ion channelopathies involving sodium (SCN4A), calcium (CACNA1S, RYR1), potassium (KCNJ2, KCNE3, KCNJ18), and chloride (CLCN1) channels, as well as sodium–potassium ATPase (ATP1A2) mutations have been implicated in periodic paralysis. 1,2…”

Section: Introductionmentioning

confidence: 99%

Two Cases of Periodic Paralysis Associated With MCM3AP Variants

Oishi,

Pagano,

Sellers

et al. 2023

Journal of Clinical Neuromuscular Disease

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Objectives: Periodic paralysis is a rare genetic condition characterized by episodes of neuromuscular weakness, often provoked by electrolyte abnormalities, physiologic stress, physical exertion, and diet. In addition to mutations in genes coding for skeletal muscle ion channels, in 2019, Gustavasson et al discovered that the MCM3AP gene could be responsible for periodic paralysis. In this study, we present 2 individuals with clinical episodes of periodic paralysis who have variants in the MCM3AP gene. Methods: Two unrelated probands were independently evaluated with clinical, genetic, and electrodiagnostic testing. Results: Proband 1 is a 46-year-old man who presented with decades of ongoing episodic weakness and fatigue, clinically diagnosed with periodic paralysis and supported by electrodiagnostic studies. Proband 2 is a 34-year-old woman with a history of episodic paralysis since childhood. Genetic testing in both individuals revealed potentially pathogenic variants in the MCM3AP gene. Conclusions: Periodic paralysis is a condition that significantly affects the lives of those diagnosed. The results illustrate that MCM3AP gene variants can been associated with a clinical and electrodiagnostic presentation of periodic paralysis. Additional future research should focus on clarifying any relationship between these genetic variants and the disease, as well as other possible genetic causes.

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Jacobsen syndrome with bilateral periventricular white matter lesions

Lee

et al. 2021

World J Pediatr

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Teaching NeuroImages: A rare case of Jacobsen syndrome with global diffuse hypomyelination of brain

Abstract: An 8-month-old boy presented with developmental delay, diffuse hypotonia, hypoplastic left heart syndrome, undescended testes, neonatal thrombocytopenia, and unusual facies. Chromosome microarray showed an 11q23-11q24 deletion, consistent with Jacobsen syndrome (JS).

Cited by 6 publications

References 2 publications

Megalencephalic leukoencephalopathy with subcortical cysts: a variant update and review of the literature

Megalencephalic leukoencephalopathy with subcortical cysts: a variant update and review of the literature

Two Cases of Periodic Paralysis Associated With MCM3AP Variants

Jacobsen syndrome with bilateral periventricular white matter lesions

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