Andermann syndrome, also known as agenesis of corpus callosum with neuronopathy (ACCPN) and Charlevoix disease, among other names, is a very rare
neurodegenerative
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
hypotonia
Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases a ...
*
areflexia
Hyporeflexia is the reduction or absence of normal bodily reflexes (areflexia). It can be detected through the use of a reflex hammer and is the opposite of hyperreflexia.
Hyporeflexia is generally associated with a deficit in the lower motor neu ...
*
amyotrophy
Amyotrophy is progressive wasting of muscle tissues. Muscle pain is also a symptom. It can occur in middle-aged males with type 2 diabetes. It also occurs with motor neuron disease.
Differential diagnosis
The following are considered differenti ...
corpus callosum
The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental mam ...
* mild to severe intellectual and developmental delay
* psychiatric problems including paranoid delusions, depression, hallucinations and autistic-like behavior
Genetics
The inheritance pattern is
autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
. Several genes have been associated with the disorder, including '' SLC12A6''.
Neuropathology
Autopsy examination of eight cases has shown both developmental and degenerative neuropathologic features in this disease, consistent with clinical duality as both a
neurodevelopmental
The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The fie ...
and
neurodegenerative
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
disorder.
In the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
, accompanying the
hypotonia
Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases a ...
at birth is
hypoplasia
Hypoplasia (from Ancient Greek ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.corticospinal tracts. Another developmental feature is seen in the
corpus callosum
The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental mam ...
, which varies from
absent
Absence may refer to:
Employment
* Leave of absence, a period of time away from a job
* Absenteeism, the habitual pattern of absence from work or duty
* Absence rate, the ratio of workers with absences to total employees
Sciences and philosophy
...
to
hypoplastic
Hypoplasia (from Ancient Greek :wikt:ὑπό, ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.anterior commissure
The anterior commissure (also known as the precommissure) is a white matter tract (a bundle of axons) connecting the two temporal lobes of the cerebral hemispheres across the midline, and placed in front of the columns of the fornix. In most exist ...
is almost always absent, but occasionally hypoplastic. A bundle of Probst can be found running anteroposterior rather than crossing the midline. The axonal damage due to the channel deficiency can cause a reactive axonal overgrowth leading to small, tumor-like growths, or tumorlets, called axonomas, or balls of aberrant axons. Damaged axons can also show a sign of inhibition of
axonal transport
Axonal transport, also called axoplasmic transport or axoplasmic flow, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other organelles to and from a neuron's cell body, through the cytopla ...
, forming
axonal spheroid
Axonal transport, also called axoplasmic transport or axoplasmic flow, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other organelles to and from a neuron's cell body, through the cytopl ...
s. These spheroids can occur throughout the cerebral hemispheres, explaining the psychotic symptoms by disconnection of the brain from itself by axonal functional disruption.
In the
peripheral nervous system
The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...
(PNS), the disease is more severe. While most nervous system diseases affect either
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
(CNS) or PNS, this disease affects both, but the changes in the PNS lead to death. This occurs by axonal disease paralyzing the
skeletal muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
s, including the
respiratory muscles
The muscles of respiration are the muscles that contribute to inhalation and exhalation, by aiding in the expansion and contraction of the thoracic cavity. The diaphragm and, to a lesser extent, the intercostal muscles drive respiration during q ...
, as a result of axonal damage in peripheral nerves. Changes in the axons are more severe in the PNS than CNS, and under the electron microscope, some axons look necrotic, by virtue of containing mitochondrial flocculent densities and other irreversible changes. The lack of innervation of the body musculature during development gives rise to small body weights, often below , remarkable in view of the preserved brain weights.
Diagnosis
A typical diagnostic workup includes:
* Clinical features
* Electrophysiologic testing
* Molecular genetic testing (''SLC12A6'')
* Magnetic resonance imaging of the brain (revealing in 60% of the patients callosal agenesis and in 10% partial callosal agenesis)
Treatment
Currently, no cure is known, but some symptoms may be treated, such as
neuroleptics
Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...
for the psychiatric problems.
Prognosis
The prognosis is poor. Patients are usually wheelchair bound by their 20s and die by their 30s.
Prevalence
The prevalence rate has been estimated to be less than one per 1,000,000 worldwide, and is much more common in the
French-Canadian
French Canadians (referred to as Canadiens mainly before the twentieth century; french: Canadiens français, ; feminine form: , ), or Franco-Canadians (french: Franco-Canadiens), refers to either an ethnic group who trace their ancestry to Fr ...
population of the Saguenay and Lac-St-Jean regions of Quebec, Canada, where it has a frequency of about one in 2100 in live births, and a carrier rate of one in 23.
OMIM
Online Mendelian Inheritance in Man (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, with a particular focus on the gene-phenotype relationship. , approximately 9,000 of the over 25,000 entries in OMIM r ...