Agenesis of the corpus callosum
Encyclopedia
Agenesis of the corpus callosum (ACC) is a rare birth defect (congenital disorder
) in which there is a complete or partial absence of the corpus callosum
. Agenesis of the corpus callosum occurs when the corpus callosum, the band of white matter connecting the two hemispheres
in the brain
, fails to develop normally, typically during pregnancy. The development of the fibers which would otherwise form the corpus callosum become longitudinally oriented within each hemisphere and form structures called Probst bundles.
In addition to agenesis of the corpus callosum, other callosal disorders include hypogenesis (partial formation), dysgenesis
(malformation) of the corpus callosum, and hypoplasia
(underdevelopment) of the corpus callosum.
, or prenatal MRI.
s, both genetic syndromes
and genetic diseases
, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause
despite the widely varying symptoms
apparent on clinical examination. Agenesis of the corpus callosum is one such disease, part of an emerging class of diseases called ciliopathies
. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell
organelle
s which are present in many cellular types throughout the human
body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia
, Bardet-Biedl syndrome
, polycystic kidney
and liver disease
, nephronophthisis
, Alstrom syndrome
, Meckel-Gruber syndrome and some forms of retinal degeneration
.
), poor motor coordination
, delays in motor milestones such as sitting and walking, low perception of pain, delayed toilet training, and chewing and swallowing difficulties. Laboratory research has demonstrated that individuals with ACC have difficulty transferring more complex information from one hemisphere to the other. They also have been shown to have some cognitive disabilities (difficulty in complex problem solving) and social difficulties (missing subtle social cues), even when their Intelligence Quotient is normal. Recent research suggests that specific social difficulties may be a result of impaired face processing
. The unusual social behavior in childhood is often mistaken for or misdiagnosed as Asperger syndrome
or other autism spectrum disorders. Other characteristics sometimes associated with callosal disorders include seizures, spasticity
, early feeding difficulties and/or gastric reflux, hearing impairments, abnormal head and facial features, and mental retardation.
, Andermann syndrome, Shapiro syndrome
, acrocallosal syndrome
, septo-optic dysplasia
(optic nerve hypoplasia
), Mowat-Wilson syndrome
and Menkes syndrome. Some conditions that are sometimes associated with ACC include maternal nutritional deficiencies
or infection
s, metabolic disorders, fetal alcohol syndrome
, craniofacial abnormalities, and other oral and maxillofacial pathologies.
, occupational therapists, physical therapists
, speech and language pathologists
, pediatricians
, geneticist
s, special educators
, early childhood intervention specialists
, and caregiver
s for adults.
varies depending on the type of callosal abnormality and associated conditions or syndromes. It is not possible for the corpus callosum to regenerate (i.e. the corpus callosum will not regrow). Neuropsychological testing reveals subtle differences in higher cortical function compared to individuals of the same age and education without ACC,
although some individuals with callosal disorders have average intelligence and lead normal lives,
, inspiration for the film Rain Man
and renowned for his savant abilities, was born with agenesis of the corpus callosum, along with macrocephaly
and damage to the cerebellum
.
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
) in which there is a complete or partial absence of the corpus callosum
Corpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
. Agenesis of the corpus callosum occurs when the corpus callosum, the band of white matter connecting the two hemispheres
Cerebral hemisphere
A cerebral hemisphere is one of the two regions of the eutherian brain that are delineated by the median plane, . The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres has an outer layer of grey matter called the cerebral cortex that is...
in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, fails to develop normally, typically during pregnancy. The development of the fibers which would otherwise form the corpus callosum become longitudinally oriented within each hemisphere and form structures called Probst bundles.
In addition to agenesis of the corpus callosum, other callosal disorders include hypogenesis (partial formation), dysgenesis
Dysgenesis
Dysgenesis may refer to:* Dysgenesis , which indicates abnormal organ development during embryonic growth and development* Anterior segment dysgenesis, a failure of the normal development of the tissues of the anterior segment of the eye...
(malformation) of the corpus callosum, and hypoplasia
Hypoplasia
Hypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
(underdevelopment) of the corpus callosum.
Diagnosis
Callosal disorders can only be diagnosed through a brain scan. They may be diagnosed through an MRI, CT scan, prenatal ultrasoundObstetric ultrasonography
Obstetric sonography is the application of medical ultrasonography to obstetrics, in which sonography is used to visualize the embryo or foetus in its mother's uterus...
, or prenatal MRI.
Cause
Agenesis of the corpus callosum is caused by disruption to development of the fetal brain between the 3rd and 12th week of pregnancy. In most cases, it is not possible to know what caused an individual to have ACC or another callosal disorder. However, research suggests that some possible causes may include chromosome errors, inherited genetic factors, prenatal infections or injuries, prenatal toxic exposures, structural blockage by cysts or other brain abnormalities, and metabolic disorders.Relation to other rare disorders: genetic ciliopathy
Until recently, the medical literature did not indicate a connection among many genetic disorderGenetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s, both genetic syndromes
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
and genetic diseases
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
, that are now being found to be related. As a result of new genetic research, some of these are, in fact, highly related in their root cause
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
despite the widely varying symptoms
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
apparent on clinical examination. Agenesis of the corpus callosum is one such disease, part of an emerging class of diseases called ciliopathies
Ciliopathy
A ciliopathy is a genetic disorder of the cellular cilia or the cilia anchoring structures, the basal bodies, or of ciliary function.Although ciliopathies are usually considered to involve proteins that localize to the primary cilia or centrosomes, it is possible for ciliopathies to be associated...
. The underlying cause may be a dysfunctional molecular mechanism in the primary cilia structures of the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
s which are present in many cellular types throughout the human
Human
Humans are the only living species in the Homo genus...
body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases. Known ciliopathies include primary ciliary dyskinesia
Primary ciliary dyskinesia
Primary ciliary dyskinesia , also known as immotile ciliary syndrome or Kartagener Syndrome ', is a rare, ciliopathic, autosomal recessive genetic disorder that causes a defect in the action of the cilia lining the respiratory tract and fallopian tube, and also of the flagella of sperm in...
, Bardet-Biedl syndrome
Bardet-Biedl syndrome
The Bardet–Biedl syndrome is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized principally by obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal failure in some cases.-Summary of the...
, polycystic kidney
Polycystic kidney disease
Autosomal dominant polycystic kidney disease is an inherited systemic disorder that predominantly affects the kidneys, but may affect other organs including the liver, pancreas, brain, and arterial blood vessels...
and liver disease
Polycystic liver disease
Polycystic liver disease usually describes the presence of multiple cysts scattered throughout normal liver tissue, in association with polycystic kidney disease.-Pathophysiology:Associations with PRKCSH and SEC63 have been described....
, nephronophthisis
Nephronophthisis
Nephronophthisis is a genetic disorder of the kidneys which affects children. It is classified as a medullary cystic kidney disease.The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause of childhood kidney failure.It is a form of...
, Alstrom syndrome
Alstrom syndrome
Alström syndrome is a rare genetic disorder caused by mutations in the gene ALMS1. It is among the rarest genetic disorders in the world, as currently it has only 266 reported cases in medical literature and over 501 known cases in 47 countries. It was first described by Carl-Henry Alström in...
, Meckel-Gruber syndrome and some forms of retinal degeneration
Retinopathy
Retinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. Frequently, retinopathy is an ocular manifestation of systemic disease.-Pathophysiology:Causes of retinopathy are varied:...
.
Signs and symptoms
Signs and symptoms of ACC and other callosal disorders vary greatly among individuals. However, some characteristics common in individuals with callosal disorders include vision impairments, low muscle tone (hypotoniaHypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
), poor motor coordination
Motor coordination
thumb|right|Motor coordination is shown in this animated sequence by [[Eadweard Muybridge]] of himself throwing a diskMotor coordination is the combination of body movements created with the kinematic and kinetic parameters that result in intended actions. Such movements usually smoothly and...
, delays in motor milestones such as sitting and walking, low perception of pain, delayed toilet training, and chewing and swallowing difficulties. Laboratory research has demonstrated that individuals with ACC have difficulty transferring more complex information from one hemisphere to the other. They also have been shown to have some cognitive disabilities (difficulty in complex problem solving) and social difficulties (missing subtle social cues), even when their Intelligence Quotient is normal. Recent research suggests that specific social difficulties may be a result of impaired face processing
Face perception
Face perception is the process by which the brain and mind understand and interpret the face, particularly the human face.The human face's proportions and expressions are important to identify origin, emotional tendencies, health qualities, and some social information. From birth, faces are...
. The unusual social behavior in childhood is often mistaken for or misdiagnosed as Asperger syndrome
Asperger syndrome
Asperger's syndrome that is characterized by significant difficulties in social interaction, alongside restricted and repetitive patterns of behavior and interests. It differs from other autism spectrum disorders by its relative preservation of linguistic and cognitive development...
or other autism spectrum disorders. Other characteristics sometimes associated with callosal disorders include seizures, spasticity
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
, early feeding difficulties and/or gastric reflux, hearing impairments, abnormal head and facial features, and mental retardation.
Associated syndromes and conditions
Some syndromes that frequently include ACC are Aicardi syndromeAicardi syndrome
Aicardi syndrome is a rare genetic malformation syndrome characterized by the partial or complete absence of a key structure in the brain called the corpus callosum, the presence of retinal abnormalities, and seizures in the form of infantile spasms...
, Andermann syndrome, Shapiro syndrome
Shapiro syndrome
The Shapiro syndrome is a rare disorder consisting of paroxysmal hypothermia , epilepsy, and agenesis of the corpus callosum with onset typically on adulthood. The disease affects about 50 people worldwide...
, acrocallosal syndrome
Acrocallosal syndrome
Acrocallosal syndrome is a rare autosomal recessive syndrome characterized by corpus callosum agenesis, polydactyly, multiple dysmorphic features, motor and mental retardation, and other symptoms. The syndrome was first described by Albert Schinzel in 1979.It is associated with GLI3.-External links:...
, septo-optic dysplasia
Septo-optic dysplasia
Septo-optic dysplasia , also known as de Morsier syndrome is a congenital malformation syndrome made manifest by hypoplasia of the optic nerve and absence of the septum pellucidum...
(optic nerve hypoplasia
Optic nerve hypoplasia
Optic nerve hypoplasia is a medical condition arising from the underdevelopment of the optic nerve. This condition is the most common congenital optic nerve anomaly. The optic disc appears abnormally small, because not all the optic nerve axons have developed properly...
), Mowat-Wilson syndrome
Mowat-Wilson Syndrome
Mowat Wilson syndrome is a rare genetic disorder that was clinically delineated by Dr. D. R. Mowat and Dr. M. J. Wilson in 1998.-Presentation:...
and Menkes syndrome. Some conditions that are sometimes associated with ACC include maternal nutritional deficiencies
Maternal nutrition
Maternal nutrition is the dietary intake and habits of expectant mothers with dual emphasis on the health of the mother and the physical and mental development of infants...
or infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s, metabolic disorders, fetal alcohol syndrome
Fetal alcohol syndrome
Fetal alcohol syndrome is a pattern of mental and physical defects that can develop in a fetus in association with high levels of alcohol consumption during pregnancy. Current research also implicates other lifestyle choices made by the prospective mother...
, craniofacial abnormalities, and other oral and maxillofacial pathologies.
Treatment
There are currently no specific medical treatments for callosal disorders, but individuals with ACC and other callosal disorders may benefit from a range of developmental therapies, educational support, and services. It is important to consult with a variety of medical, health, educational and social work professionals. Such professionals include neurologists, neuropsychologistsNeuropsychology
Neuropsychology studies the structure and function of the brain related to specific psychological processes and behaviors. The term neuropsychology has been applied to lesion studies in humans and animals. It has also been applied to efforts to record electrical activity from individual cells in...
, occupational therapists, physical therapists
Physical therapy
Physical therapy , often abbreviated PT, is a health care profession. Physical therapy is concerned with identifying and maximizing quality of life and movement potential within the spheres of promotion, prevention, diagnosis, treatment/intervention,and rehabilitation...
, speech and language pathologists
Speech and language pathology
Speech-Language Pathology specializes in communication disorders.The main components of speech production include: phonation, the process of sound production; resonance, opening and closing of the vocal folds; intonation, the variation of pitch; and voice, including aeromechanical components of...
, pediatricians
Pediatrics
Pediatrics or paediatrics is the branch of medicine that deals with the medical care of infants, children, and adolescents. A medical practitioner who specializes in this area is known as a pediatrician or paediatrician...
, geneticist
Geneticist
A geneticist is a biologist who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a researcher or lecturer. Some geneticists perform experiments and analyze data to interpret the inheritance of skills. A geneticist is also a Consultant or...
s, special educators
Special education
Special education is the education of students with special needs in a way that addresses the students' individual differences and needs. Ideally, this process involves the individually planned and systematically monitored arrangement of teaching procedures, adapted equipment and materials,...
, early childhood intervention specialists
Early Childhood Intervention
Early childhood intervention is a support system for children with developmental disabilities or delays and their families.The mission of Early Childhood Intervention is to assure that families who have children ages birth to three, with diagnosed disabilities, developmental delays or substantial...
, and caregiver
Caregiver
Caregiver may refer to:* Caregiver or carer - an unpaid person who cares for someone requiring support due to a disability, frailty, mental health problem, learning disability or old age...
s for adults.
Prognosis
PrognosisPrognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
varies depending on the type of callosal abnormality and associated conditions or syndromes. It is not possible for the corpus callosum to regenerate (i.e. the corpus callosum will not regrow). Neuropsychological testing reveals subtle differences in higher cortical function compared to individuals of the same age and education without ACC,
although some individuals with callosal disorders have average intelligence and lead normal lives,
Notable cases
Kim PeekKim Peek
Laurence Kim Peek was an American savant. Known as a "megasavant", he had a photographic or eidetic memory, but also social difficulties, possibly resulting from a developmental disability related to congenital brain abnormalities. He was the inspiration for the character of Raymond Babbitt,...
, inspiration for the film Rain Man
Rain Man
Rain Man is a 1988 drama film written by Barry Morrow and Ronald Bass and directed by Barry Levinson. It tells the story of an abrasive and selfish yuppie, Charlie Babbitt, who discovers that his estranged father has died and bequeathed all of his multimillion-dollar estate to his other son,...
and renowned for his savant abilities, was born with agenesis of the corpus callosum, along with macrocephaly
Macrocephaly
Macrocephaly , occurs when the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.-Causes:...
and damage to the cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
.
External links
Support organizations:- National Organization for Disorders of the Corpus Callosum Non - profit US organisation offering information and support.
- Corpal UK charity offering support to families caring for children with ACC.
- Agenesis of the Corpus Callosum Community A site with message boards for discussing ACC.
- ACC page from Contact a Family UK charity providing support and advice to families with disabled children or those with special needs.
- Aicardi Syndrome Foundation Support and information for families caring for children with Aicardi Syndrome.
- UCSF Fetal Treatment Center: Agenesis of the corpus callosum
- Caregiver Support and Personal Stories - Personal experiences of those affected by Agenesis of Corpus Callosum