Familial Dysautonomia in Review: Diagnosis and Treatment of Ocular Manifestations

Josaitis, Cathleen A.; Matisoff, Martin

doi:10.1007/978-1-4615-0717-8_9

Cited by 15 publications

(5 citation statements)

References 27 publications

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“… 35 , 47 , 48 Initially, it was reported that the loss of vision in FD resulted from corneal opacities, neovascularization, and sensory defects such as corneal analgesia, severe dry eye, ulceration healing, and incomplete closure of eyelids. 49 , 50 , 51 , 52 , 53 However, recent detailed studies have shown that decreased visual acuity, loss of central vision, and temporal optic nerve pallor occur in individuals with FD even without any corneal complications, suggesting a neuro-ophthalmic nature of the disease. 47 In FD, visual impairment is usually early onset and often progresses to legal blindness in the third decade of life.…”

Section: Introductionmentioning

confidence: 99%

Development of an oral treatment that rescues gait ataxia and retinal degeneration in a phenotypic mouse model of familial dysautonomia

Morini¹,

Chekuri²,

Logan³

et al. 2023

The American Journal of Human Genetics

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Section: Introductionmentioning

confidence: 99%

Development of an oral treatment that rescues gait ataxia and retinal degeneration in a phenotypic mouse model of familial dysautonomia

Morini¹,

Chekuri²,

Logan³

et al. 2023

The American Journal of Human Genetics

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“…Common symptoms include gastrointestinal dysfunction, gastroesophageal reflux, vomiting crises, recurrent pneumonia, seizures, gait abnormalities, kyphoscoliosis, postural hypotension, hypertension crises, absence of fungiform papillae on the tongue, decreased deeptendon reflexes, defective lacrimation and impaired pain and temperature perception (3,(23)(24)(25)(26)(27)(28)(29) Despite this complex neurological phenotype, FD patients also suffer from progressive visual dysfunction that severely affects their quality of life (30)(31)(32). Initially, it was reported that the loss of vision in FD patients resulted from corneal opacities, neovascularization and sensory defects such as corneal analgesia, severe dry eye, ulceration healing and incomplete closure of eye lids (33)(34)(35)(36)(37). However, recent detailed studies have shown that decreased visual acuity, loss of central vision, and temporal optic nerve pallor occur in FD patients even without any corneal complications, suggesting a neuro-ophthalmic nature of the disease (31).…”

Section: Introductionmentioning

confidence: 99%

Selective retinal ganglion cell loss and optic neuropathy in a humanized mouse model of familial dysautonomia

Chekuri

et al. 2021

Preprint

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Familial dysautonomia (FD) is an autosomal recessive neurodegenerative disease caused by a splicing mutation in the gene encoding Elongator complex protein 1 (ELP1, also known as IKBKAP). This mutation results in tissue-specific skipping of exon 20 with a corresponding reduction of ELP1 protein, predominantly in the central and peripheral nervous system. Although FD patients have a complex neurological phenotype caused by continuous depletion of sensory and autonomic neurons, progressive visual decline leading to blindness is one of the most problematic aspect of the disease, as it severely affects their quality of life. To better understand the disease mechanism as well as to test the in vivo efficacy of targeted therapies for FD, we have recently generated a novel phenotypic mouse model, TgFD9; Elp1Δ20/flox. This mouse exhibits most of the clinical features of the disease and accurately recapitulates the tissue-specific splicing defect observed in FD patients. Driven by the dire need to develop therapies targeting retinal degeneration in FD, herein, we comprehensively characterized the progression of the retinal phenotype in this mouse, and we demonstrated that it is possible to correct ELP1 splicing defect in the retina using the splicing modulator compound (SMC) BPN-15477.

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“…Ocular FD manifestations including progressive optic neuropathy which are a prominent feature of FD. 34,35 Since neuro-ophthalmologic status monitoring is important, it is recommended that FD patients receive only a 50% diluted dose of tropicamide or an effective alternative drug.…”

Section: A B Histamine H2 Antagonists and Serotonin (5-ht 4) Receptormentioning

confidence: 99%

Uncommon side effects of common drugs in patients with familial dysautonomia

Perl

Hakimian

Maayan

et al. 2021

Pharmacoepidemiology and Drug

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Purpose: Patients with the autosomal recessive disorder of familial dysautonomia typically exhibit exacerbated adverse side effects to many common drugs. We aimed to catalog these adverse effectswith a focus on common drugs that are frequently administered to FD patients and compare their incidences to those within the general population.Methods: We used data of 595 FD patients from an international database with information on drugs received and adverse effects. To investigate the molecular causes of reported differences in drug responses in FD patients, we used expression microarrays to compare the mRNA expression profiles in peripheral blood leukocytes of FD patients (n = 12) and healthy individuals (n = 10).Results: Several drug classes, including cholinergics, anti-cholinergics, anti-convulsants, methylxanthines, SSRIs, and antibiotics caused either unreported symptoms or elevated rates of adverse events in FD patients. FD patients experienced different or more frequent adverse side effects than the general population in 31/123 drugs.These side effects included blood cell dyscrasias, amenorrhea, gastrointestinal bleeding, and bronchospasm. New findings include enhanced reaction of FD patients to H2 antagonist agents and to serotonin receptor agonists. We also detected eight genes differentially expressed between FD patients and healthy individuals that may underlie the differential drug responses of FD patients. Conclusion:We provide evidence that suggests the use of several common drugs should be discontinued or reduced in FD patients.There were no prior presentations, sponsors or grants for this research.

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Familial Dysautonomia in Review: Diagnosis and Treatment of Ocular Manifestations

Cited by 15 publications

References 27 publications

Development of an oral treatment that rescues gait ataxia and retinal degeneration in a phenotypic mouse model of familial dysautonomia

Development of an oral treatment that rescues gait ataxia and retinal degeneration in a phenotypic mouse model of familial dysautonomia

Selective retinal ganglion cell loss and optic neuropathy in a humanized mouse model of familial dysautonomia

Uncommon side effects of common drugs in patients with familial dysautonomia

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