Related Experiment Video
Updated: Jul 5, 2026
07:26
Systematic Assessment of Mammalian Skull Specimens for Dental and Temporomandibular Joint Pathology
Published on: August 22, 2022
Increased severity over generations of Charcot-Marie-Tooth disease type 1A
I Steiner1, M Gotkine, B Steiner-Birmanns
1Neurological Sciences Unit, Hadassah University Hospital, Mount Scopus, 24035, Jerusalem 91240, Israel. isteiner@md2.huji.ac.il
Journal of Neurology
|April 29, 2008
Summary
Clinical anticipation, an increase in disease severity over generations, was observed in a subgroup of Charcot-Marie-Tooth type 1A (CMT1A) patients. This suggests earlier onset and greater severity in younger generations of CMT1A families.
Area of Science:
- Genetics
- Neurology
- Clinical Medicine
Background:
- Charcot-Marie-Tooth type 1A (CMT1A) is an inherited polyneuropathy caused by a duplication on chromosome 17p11.2, affecting the PMP22 gene.
- The genetic mutation responsible for CMT1A is stable and not altered during inheritance.
Purpose of the Study:
- To investigate the hypothesis of clinical anticipation in Charcot-Marie-Tooth type 1A (CMT1A).
- To determine if disease severity increases across generations in CMT1A families.
Main Methods:
- Evaluated 39 CMT1A mutation-positive patients from 16 families, including 23 parent-offspring pairs.
- Assessed age of onset through patient interviews and measured clinical severity using the CMT neuropathy score (CMTNS).
Main Results:
- An earlier age of presentation was noted in children compared to parents in 21/23 pairs and 14/16 families.
- The mean age of onset was significantly earlier in the younger generation (12.61 years) versus the parent generation (41.22 years).
- A statistically significant trend towards worse clinical phenotype in the younger generation was observed after adjusting for age differences.
Conclusions:
- Findings suggest clinical anticipation, an increase in disease severity over generations, in a subgroup of CMT1A patients.
- The underlying mechanism for this observed clinical anticipation in CMT1A remains undetermined.
- Further validation in a larger cohort of CMT1A families is recommended.
Related Concept Videos
01:26Type I Diabetes II: Pathophysiology
Type 1 diabetes mellitus arises from an immune-mediated destruction of pancreatic β-cells, resulting in an absolute deficiency of insulin. This process develops in genetically susceptible individuals when autoimmunity, environmental exposures, and immunologic dysregulation converge to trigger a targeted attack on the insulin-producing cells of the pancreas. The β-cells are located within the islets of Langerhans and are essential for regulating blood glucose by facilitating cellular uptake of...
01:29Alzheimer Disease l: Introduction
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
01:23Alzheimer Disease ll: Pathophysiology
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
01:21Chronic Pancreatitis II: Pathophysiology
Chronic pancreatitis is a progressive and irreversible inflammation of the pancreas, most often caused by long-term alcohol abuse, but it can also be related to ductal obstruction, smoking, or genetic factors.Chronic pancreatitis occurs when the pancreas is repeatedly exposed to harmful agents like alcohol, smoking, ductal obstruction, or genetic predisposition. These factors lead to the release of toxic metabolites and inflammatory cytokines, sustaining chronic inflammation in the pancreatic...
01:21Huntington Disease l: Introduction
Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
01:23Cystic Fibrosis: Pathogenesis
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...