Pelizaeus-Merzbacher disease in siblings

Mittal, Amit; Maini, Baljeet; Sharma, Praveen; Aggarwal, Aruna

doi:10.4103/1817-1745.76122

Cited by 3 publications

(6 citation statements)

References 3 publications

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“…The presenting symptoms, developmental milestones achieved, and progression of symptoms reported in our cohort were consistent with many previous studies of patients with PLP1 duplications. All our patients exhibited onset within the first year of life, with nystagmus predominating as the first symptom noticed, consistent with previous reports 7,8,10,11 . In addition, most had nystagmus at some point in their lives and all had hypotonia, key characteristics of the classic PMD phenotype.…”

Section: Discussionsupporting

confidence: 91%

The natural history of Pelizaeus–Merzbacher disease caused by PLP1 duplication: A multiyear case series

Trepanier,

Aguilar,

Kamholz

et al. 2023

Clinical Case Reports

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Key Clinical MessageThis study aimed to characterize the clinical features, developmental milestones, and the natural history of Pelizaeus–Merzbacher disease (PMD) associated with PLP1 gene duplications. The study examined 16 PMD Patients ranging in age from 7 to 48 years, who had a documented PLP1 gene duplication. The study examined and analyzed the medical and developmental histories of the subjects utilizing a combination of resources that included medical history questionnaires, medical record reviews, and a 31‐point functional disability scale that had been previously validated. The data extracted from the medical records and questionnaires for analysis included information related to medical and developmental histories, level of ambulation and cognition, and degree of functional disability. The summation of findings among the study population demonstrated that the presenting symptoms, developmental milestones achieved, and progression of symptoms reported are consistent with many previous studies of patients with PLP1 duplications. All patients exhibited onset within the first year of life, with nystagmus predominating as the first symptom noticed. All patients exhibited delays in both motor and language development; however, many individuals were able to meet several developmental milestones. They exhibited some degree of continued motor impairment with none having the ability to walk independently. All patients were able to complete at least some of the cognition achievements and although not all were verbal, a number were able to use communication devices to complete these tasks. A critical tool of the study was the functional disability scale which provided a major advantage in helping quantify the clinical course of PMD, and for several, we were able to gather this information at more than one point in time. These reported findings in our cohort contribute important insight into the clinical heterogeneity and potential underlying mechanisms that define the molecular pathogenesis of the disease. This is one of only a small number of natural history studies examining the clinical course of a cohort of patients with PLP1 duplications within the context of a validated functional disability scoring system. This study is unique in that it is limited to subjects with PLP1 gene duplications. This study demonstrated many commonalities to other studies that have characterized the features of PMD and other PLP1‐related disorders but also provide significant new insights into the evolving story that marks the natural history.

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Section: Discussionsupporting

confidence: 91%

The natural history of Pelizaeus–Merzbacher disease caused by PLP1 duplication: A multiyear case series

Trepanier,

Aguilar,

Kamholz

et al. 2023

Clinical Case Reports

View full text Add to dashboard Cite

show abstract

“…All our patients exhibited onset within the first year of life, with nystagmus predominating as the first symptom noticed, consistent with previous reports. 7,8,10,11 In addition, most had nystagmus at some point in their lives and all had hypotonia, key characteristics of the classic PMD phenotype. In our cohort, all of our subjects exhibited delays in both motor and language development; however, many individuals were able to meet several developmental milestones.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to previous studies, a subset of the PMD patients in our study were able to obtain head control, the ability to sit, the ability to speak several words or sentences, and some were even able to walk with assistance. 7,8,11,13 All individuals exhibited some degree of continued motor impairment with none of the participants having the ability to walk independently. We found that all individuals relied on the use of wheelchairs for most or all their ambulation.…”

Section: Discussionmentioning

confidence: 99%

“…They can, however, can be loosely grouped into three main clinical phenotypes : 1) classic PMD, characterized by nystagmus, hypotonia, and delay in motor development with onset in the first year of life 6,7 2) connatal PMD characterized by severe hypotonia and stridor with onset at birth, and death within the first ten years of life. 6,8 , and 3) SPG2, characterized by a slowly progressive X-linked spastic paraparesis 3,6,8 Classic PMD is usually caused by a duplication of the PLP1 gene within its locus on the X-chromosome. The mechanism(s) causing disease are not clear, but may be associated with alterations in oligodendrocyte energy metabolism.…”

Section: Introductionmentioning

confidence: 99%

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The Natural History of Pelizaeus-Merzbacher Disease

Trepanier

Aguilar

Kamholz

et al. 2023

Preprint

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“…Pelizaeus‐Merzbacher disease (PMD; OMIM 312080), first described in the same family by Pelizaeus in 1885 and later by Merzbacher in 1910, is a recessive X‐linked leukodystrophy of the central nervous system, with an estimated incidence of 1 in 770,000 live births (Heim et al,1997). In PMD, normal myelination does not occur during development of the central nervous system (Takanashi et al,1999), in contrast to other leukodystrophies such as metachromatic leukodystrophy, adrenoleukodystrophy, and multiple sclerosis, in which myelin is formed and then broken down (Mittal et al,2010). Typically affected males exhibit early onset nystagmus and hypotonia, later evolving into spastic tetraparesis, dystonia, and ataxia with developmental delay usually initiating within the first year (Shimojima et al,2010).…”

Section: Introductionmentioning

confidence: 99%

Familial Pelizaeus–Merzbacher disease caused by a 320.6‐kb Xq22.2 duplication and the pathological findings of a male fetus

Kitsiou-Tzeli

Konstantinidou

Sofocleous

et al. 2012

Birth Defects Research

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Genotype-phenotype correlation is provided. In the connatal form of PMD, leukodystrophy and cerebellar atrophy can occur antenatally and be established at 25 weeks' gestation. The observation of degenerative brain lesions occurring before the onset of subcortical myelination suggests that the PLP1 gene has a more complex role in human brain development, exceeding its structural function in myelin formation.

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Pelizaeus-Merzbacher disease in siblings

Cited by 3 publications

References 3 publications

The natural history of Pelizaeus–Merzbacher disease caused by PLP1 duplication: A multiyear case series

The natural history of Pelizaeus–Merzbacher disease caused by PLP1 duplication: A multiyear case series

The Natural History of Pelizaeus-Merzbacher Disease

Familial Pelizaeus–Merzbacher disease caused by a 320.6‐kb Xq22.2 duplication and the pathological findings of a male fetus

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