Familial dysautonomia.

Clin Auton Res

Department of Neurology, Dysautonomia Center, New York University School of Medicine, New York, NY, USA.

Published: June 2023

AI Article Synopsis

  • - Familial dysautonomia (FD) is a genetic disorder primarily affecting individuals of Ashkenazi Jewish descent, leading to severe sensory loss and other autonomic dysfunctions due to a mutation in the ELP1 gene.
  • - Symptoms include extreme blood pressure fluctuations, respiratory issues from swallowing difficulties, and episodes of autonomic crises, leading to complications like blindness and impaired movement.
  • - Current treatments focus on managing symptoms, although new therapies targeting the underlying mutation are on the horizon, with early intervention seen as vital for effectiveness.

Article Abstract

Familial dysautonomia (FD) is an autosomal recessive hereditary sensory and autonomic neuropathy (HSAN, type 3) expressed at birth with profound sensory loss and early death. The FD founder mutation in the ELP1 gene arose within the Ashkenazi Jews in the sixteenth century and is present in 1:30 Jews of European ancestry. The mutation yield a tissue-specific skipping of exon 20 and a loss of function of the elongator-1 protein (ELP1), which is essential for the development and survival of neurons. Patients with FD produce variable amounts of ELP1 in different tissues, with the brain producing mostly mutant transcripts. Patients have excessive blood pressure variability due to the failure of the IXth and Xth cranial nerves to carry baroreceptor signals. Neurogenic dysphagia causes frequent aspiration leading to chronic pulmonary disease. Characteristic hyperadrenergic "autonomic crises" consisting of brisk episodes of severe hypertension, tachycardia, skin blotching, retching, and vomiting occur in all patients. Progressive features of the disease include retinal nerve fiber loss and blindness, and proprioceptive ataxia with severe gait impairment. Chemoreflex failure may explain the high frequency of sudden death in sleep. Although 99.5% of patients are homozygous for the founder mutation, phenotypic severity varies, suggesting that modifier genes impact expression. Medical management is currently symptomatic and preventive. Disease-modifying therapies are close to clinical testing. Endpoints to measure efficacy have been developed, and the ELP1 levels are a good surrogate endpoint for target engagement. Early intervention may be critical for treatment to be successful.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10286-023-00941-1DOI Listing

Publication Analysis

Top Keywords

familial dysautonomia
8
founder mutation
8
dysautonomia familial
4
dysautonomia autosomal
4
autosomal recessive
4
recessive hereditary
4
hereditary sensory
4
sensory autonomic
4
autonomic neuropathy
4
neuropathy hsan
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!