Neurobehavioral characterization of adult-onset Alexander disease

Lichtenstein, Maya; Dwosh, Emily; Chowdhury, Anupama Roy; Farrer, Matthew J.; McKenzie, Michael; Guella, Ilaria; Evans, Daniel M.; Shewchuk, Jason R.; Hayden, Sherri; Barton, Jason J. S.; Feldman, Howard

doi:10.1212/cpj.0000000000000356

Cited by 4 publications

(4 citation statements)

References 8 publications

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“…This mutation occurs in the C-terminal tail domain of GFAP and is predicted to be deleterious, with a combined annotationdependent depletion score of 23.3 (CADD v1.6). The same sequence change has been reported several times in patients with AxD [1,2] but only once in the gnomAD database of controls. Ours is the first description of this mutation in a case of familial AxD.…”

supporting

confidence: 75%

Does genetic anticipation occur in familial Alexander disease?

et al. 2021

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Alexander Disease (AxD) is a rare leukodystrophy caused by missense mutations of glial fibrillary acidic protein (GFAP). Primarily seen in infants and juveniles, it can present in adulthood. We report a family with inherited AxD in which the mother presented with symptoms many years after her daughter. We reviewed the age of onset in all published cases of familial AxD and found that 32 of 34 instances of parent–offspring pairs demonstrated an earlier age of onset in offspring compared to the parent. We suggest that genetic anticipation occurs in familial AxD and speculate that genetic mosaicism could explain this phenomenon.

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supporting

confidence: 75%

Does genetic anticipation occur in familial Alexander disease?

et al. 2021

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“…Sequence analysis of Glial fibrillary acidic protein ( GFAP ) revealed a heterozygous c.1157A>G mutation (p.N386S), and he was diagnosed with AOAD. Mutation in p.N386S in AOAD has been reported previously, with variable symptoms including cognitive impairment, ataxia, and incontinence 2 . Our patient had only hyperreflexia.…”

Section: Introductionsupporting

confidence: 57%

“…Mutation in p.N386S in AOAD has been reported previously, with variable symptoms including cognitive impairment, ataxia, and incontinence. 2 Our patient had only hyperreflexia. Severity and variety of clinical presentations differ within AOAD patients.…”

Section: Introductionmentioning

confidence: 52%

Adult‐onset Alexander disease with imperceptible neurological findings

Itami

Oka

Nakagawa

et al. 2021

Neurology & Clinical Neurosc

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“…This case was initially diagnosed as a bipolar disorder but was genetically confirmed as Alexander disease after cognitive deterioration, apathy, neglect of personal care, memory loss, and bulbar and cerebellar symptoms, which emerged later in the course of the disease ( Melchionda et al,2013 ) . Also, a family study of three siblings with suspected AOAD (confirmed only with MRI) described behavioral and affective changes, such as withdrawal, apathy, flat affect, prominent mood and personality disturbances, and predominant frontal executive dysfunction (impairment of set-shifting and mental flexibility, perseveration, flat affect, and anosognosia) in the affected patients ( Lichtenstein et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Psychiatric Onset Alexander Disease: An Important Challenge in Neuropsychiatric Diagnosis: A Case Report

Arshiany

Ezzatian

Artounian

et al. 2022

BCN

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Introduction: Alexander disease is a heterogenous group of diseases with various manifestations based on age of disease onset. This rare leukodystrophy syndrome with mutations in GFAP Gene could present with developmental delay and seizure in infantile form to ataxia and bulbar palsy in adulthood. However psychiatric symptoms are not well-defined and usually evaluate after disease diagnosis not before disease investigations. Case report: Our patient is a fifty-two-year-old Iranian woman with history of depression from about 17 years ago, suicidal attempt two years ago and ingestion a large amount of opium with the intention of suicide 2 months ago who was presented with disorientation and probably delirious state in the last interview. Eventually in comprehensive investigations, white matter hyperintensity and leukodystrophy was diagnosed and ultimately to determine the cause of these changes with gene study, whole and Exon deletion of GFAP Gene Late Onset Alexander disease was determined. Conclusion: Neurological-onset manifestation of Alexander disease specifically late onset form is the most common clinical picture of disease and was seen in about 90% of patients but psychiatric symptoms are not well-known and psychiatric- onset disease was not described yet. On the other hand, various Gene Mutation were described in Late Onset Alexander Disease, however large whole Exon deletion which was revealed in our patient is a novel mutation and significantly need to be declared. Here authors describe a late onset Alexander disease with psychiatric onset symptoms and novel large Exon deletion in GFAP Gene.

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Neurobehavioral characterization of adult-onset Alexander disease

Abstract: Consider adult-onset Alexander disease in the differential diagnosis of possible behavioral-variant frontotemporal dementia.

Cited by 4 publications

References 8 publications

Does genetic anticipation occur in familial Alexander disease?

Does genetic anticipation occur in familial Alexander disease?

Adult‐onset Alexander disease with imperceptible neurological findings

Psychiatric Onset Alexander Disease: An Important Challenge in Neuropsychiatric Diagnosis: A Case Report

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