Disorders of the Corpus Callosum
Co-occurring Conditions & Genetics
Co-occurring Structural Conditions
When you have a brain-scan (MRI, CT, Ultrasound, etc.), you may receive additional information about your/your loved one’s brain structure.
Probst Bundles
Definition: “Probst bundles are the axons that should have formed the corpus callosum (Pirola et. al, 1998).” “Probst bundles are white matter fibers that normally cross the corpus callosum but (because of the agenesis of the corpus callosum) fail to cross the midline (HPO).”
Symptoms: NA
How common is it? Unknown (but only occurring in individuals with a DCC)
More info about Probst Bundles:
Interhemispheric Cyst
Definition: “Cystic collection (sac-like, fluid containing pocket of membranous tissue) located in the interhemispheric fissure, with or without communication with the ventricular system.” (HPO)
Characteristics: Variable by type and location of cyst
How common is it? Unknown
More info about Interhemispheric Cysts:
Dandy Walker Syndrome
Definition: “Dandy-Walker Syndrome (DWS) is a condition (present from birth) where the cerebellum does not develop normally. The cerebellum is an area at the back of the brain that controls movement and balance.” (Nationwide Children’s)
Characteristics:
- Too much fluid in the brain (called hydrocephalus)
- Signs of increased pressure from fluid build-up in the brain, including irritability and vomiting (usually seen in older children)
- Large head (called macrocephaly)
- Delayed crawling and walking
- Balance problems
- Stiff muscles
- Trouble with fine motor skills (picking up small objects, writing)
- Vision problems
- Seizures
- Abnormal breathing
- Jerky eye or neck movements
- Delay in mental development
- Agenesis of the corpus callosum
- Source: Nationwide Children’s
How common is it? 1 in 350,000 live births (NIH)
DCC and Dandy Walker Syndrome:
More info:
https://my.clevelandclinic.org/health/diseases/6002-dandy-walker-syndrome
https://hpo.jax.org/browse/disease/OMIM:220200
https://www.nationwidechildrens.org/conditions/dandy-walker-syndrome
Colpocephaly
Definition: “Colpocephaly is a condition present at birth in which a portion of the fluid-filled spaces (ventricles) in the back of your brain are larger than expected.” (Cleveland Clinic)
Characteristics:
- Difficulty with problem-solving
- Difficulties with attention and hyperactivity
- Speech delay
- Intellectual disability
- Challenges with coordination and movement
- Hearing issues
- Muscle spasms
- Seizures
- Small head size (microcephaly)
- Vision problems
- Often diagnosed in childhood
- Source: Cleveland Clinic
How common is it? Unknown
DCC and Colpocephaly:
“Colpocephaly is … often associated with partial or complete agenesis of the corpus callosum.” (Parker et al., 2019)
More info about Colpocephaly:
https://my.clevelandclinic.org/health/diseases/21990-colpocephaly
Ventriculomegaly
Definition: “Ventriculomegaly is a condition in which the brain ventricles, or fluid-filled cavities, are enlarged due to build up of cerebrospinal fluid (CSF). CSF is a fluid that protects the brain and spinal cord.” (Nationwide Children’s)
Characteristics:
- A rapidly growing, large head
- Full or bulging “soft spot” at the top of the head
- Bulging veins in the scalp
- Irritability or sleepiness
- Poor feeding and/or projectile vomiting
- Abnormal eye movement, such as not looking upward or always looking downward
- Developmental delays
- Source: Nationwide Children’s
How common is it? 1 in 1,000 births (The Fetal Medicine Foundation)
DCC and Ventriculomegaly:
“It [agenesis of the corpus callosum] may occur as an isolated brain problem, in combination with other brain abnormalities, such as ventriculomegaly.” (UCSF)
More info about Ventriculomegaly:
https://my.clevelandclinic.org/health/diseases/25216-ventriculomegaly
https://hpo.jax.org/browse/term/HP:0002119
https://www.nationwidechildrens.org/conditions/ventriculomegaly
Schizencephaly
Definition: “Schizencephaly is a brain malformation that’s present from birth. It causes slits (clefts) to form on the left and/or right sides of your brain. These slits fill with fluid and grey matter. Schizencephaly symptoms vary based on the size of the clefts.” (Cleveland Clinic)
Characteristics:
- A small head size.
- Weak muscle tone or a loss of strength (hemiparesis).
- Tight or stiff muscles (spasticity).
- Paralysis (part of your body or your entire body).
- Seizures.
- A buildup of fluid in your brain (hydrocephalus).
- Misalignment of your eyes (strabismus).
- Developmental delays
- Source: Cleveland Clinic
How common is it? 1.48 in 100,000 births (Howe, Rankin, & Draper, 2012)
DCC and Schizencephaly:
More info about Schizencephaly:
https://my.clevelandclinic.org/health/diseases/25013-schizencephaly
Lissencephaly
Definition: “Lissencephaly is a condition (present from birth) that causes a developing brain to appear smooth instead of having normal bumps and folds.” (Cleveland Clinic)
Characteristics:
- Seizures (epilepsy develops in the first year of life in 9 out of 10 lissencephaly cases).
- Difficulty swallowing (dysphagia) and eating.
- Developmental delays.
- Mental disability and learning differences.
- Muscle spasms.
- Issues with psychomotor functions, such as hand-eye coordination, movement and dexterity.
- Failure to thrive (slow physical development in a baby or child).
- A smaller-than-normal head size (microcephaly).
- Congenital limb differences involving their hands, fingers or toes.
- Source: Cleveland Clinic
How common is it? 1.2 in 100,000 births (Rijk-van Andel et al., 1991)
DCC and Lissencephaly:
“Infants with an ARX gene mutation have other symptoms along with lissencephaly, like missing sections of their brain (agenesis of the corpus callosum).” (Cleveland Clinic)
More info about Lissencephaly:
https://my.clevelandclinic.org/health/diseases/6033-lissencephaly
Hydrocephalus
Definition: “Hydrocephalus is the excessive accumulation of cerebrospinal fluid (CSF) within cavities of your brain called ventricles. This excess fluid causes your ventricles to widen, which puts harmful pressure on the tissues of your brain.” (Cleveland Clinic)
Characteristics:
Symptoms in infants may include:
- Unusually large head.
- Bulging soft spot (fontanel) on top of baby’s head.
- Downward gaze of baby’s eyes (sun-setting eyes).
- Vomiting.
- Sleepiness.
Symptoms in older children may include:
- Headache.
- Nausea and vomiting.
- Vision problems.
- Developmental delays.
Symptoms in adults may include:
- Headache.
- Nausea and vomiting.
- Vision problems.
- Feeling tired.
- Problems with balance and coordination.
- Short-term memory loss.
- Symptoms in older adults may include:
- Problems walking (gait disturbances).
- Mild dementia.
- Forgetfulness
- Loss of bladder control.
- Source: Cleveland Clinic
How common is it? 85 in 100,000 births; 88 per 100,000 for the pediatric population and 11 per 100,000 in adults. (NIH)
DCC and Hydrocephalus:
More info about Hydrocephalus:
https://my.clevelandclinic.org/health/diseases/17334-hydrocephalus
Holoprosencephaly
Definition: “Holoprosencephaly is a condition (present from birth) that causes the fetal brain to not properly separate into the right and left hemispheres (halves). Holoprosencephaly ranges in severity and also often causes facial development issues.” (Cleveland Clinic)
Characteristics:
- Developmental delay.
- Intellectual disability.
- Epilepsy and seizures.
- Small head (microcephaly).
- Large head (macrocephaly).
- Excessive fluid in the brain (hydrocephalus).
- Facial abnormalities.
- Tooth abnormalities (single central incisor).
- Cleft lip and/or palate.
- Problems regulating body temperature, heart rate and breathing.
- Feeding difficulties.
- Source: Cleveland Clinic
How common is it? 1 in 8,000-16,000 live births (Leoncini et al., 2008)
DCC and Holoprosencephaly:
More info about Holoprosencephaly:
https://my.clevelandclinic.org/health/diseases/22919-holoprosencephaly-hpe
Macrocephaly
Definition: “Macrocephaly means your head is larger than other people of the same age and sex. Having a larger head size can be harmless, if a larger head size is a family trait, or it can be a sign of a serious medical condition. Common medical conditions include an enlarged brain, brain bleed, fluid on the brain and genetic disorders.” (Cleveland Clinic)
Characteristics:
- Rapid head growth.
- Bulging veins on head.
- Developmental delays (not reaching learning milestones).
- A downward gaze of eyes.
- Firm or bulging spaces between the bones of skull where bone formation isn’t yet complete.
- Poor appetite.
- Having other conditions along with macrocephaly, such as epilepsy or autism.
- Source: Cleveland Clinic
How common is it? 2-3% of population (NIH)
DCC and Macrocephaly:
More info about Macrocephaly:
https://my.clevelandclinic.org/health/diseases/22685-macrocephaly
Microcephaly
Definition: “Microcephaly is a condition that causes the head to be smaller than expected. You can be born with a small head or this can become more apparent as you grow.” (Cleveland Clinic)
Characteristics:
- Seizures.
- Issues with cognitive development.
- Developmental delays (learning how to speak, stand and walk).
- Balance, movement and coordination challenges.
- Difficulty feeding or swallowing.
- Hearing or vision loss.
- Source: Cleveland Clinic
How common is it? 2.8-3.9 in 1,000 live births (Shen et al., 2021)
DCC and Microcephaly:
More info about Microcephaly:
https://my.clevelandclinic.org/health/diseases/9843-microcephaly
Absence of the Septum Pellucidum
Definition: “The absence of the septum pellucidum is a condition (present from birth) in which a thin membrane called the septum pellucidum is missing from its normal position in the middle of the brain.” (Rare Diseases)
Characteristics:
- Learning challenges
- Eye problems (e.g., abnormal development of the optic disk, rapid involuntary movement of the eyes, etc.)
- Weak muscles (i.e., low muscle tone)
- Behavioral issues
- Seizures
- Jaundice (yellowing of the skin or eyes)
- Problems with hormones (e.g., pituitary deficiencies/hormonal imbalance)
- Source: NIH
How common is it? 2-3 in 100,000 individuals (Bruyn, 1977)
DCC and Absence of the Septum Pellucidum:
More info about Absence of the Septum Pellucidum:
https://hpo.jax.org/browse/term/HP:0001331
https://rarediseases.org/mondo-disease/congenital-absence-of-septum-pellucidum/
Interhemispheric Lipoma
Definition: “Intracranial lipomas are uncommon and benign congenital malformations that … are usually located in the interhemispheric fissure, especially in the corpus callosum.” (Caballero, 2012)
Characteristics:
- Depends on size and location
- Seizures
How common is it? It accounts for 0.06%-0.46% of all intracranial tumors (Aggarwal et al., 2018)
DCC and Interhemispheric Lipoma:
Arachnoid Cyst
Definition: “An arachnoid cyst is a noncancerous fluid-filled sac that grows on the brain or spinal cord.” (Cleveland Clinic)
Characteristics:
- The vast majority of cysts don’t cause symptoms. But possible symptoms include:
- Headaches.
- Hydrocephalus (excess cerebrospinal fluid collects in the brain).
- Nausea and vomiting.
- Seizures.
- Vertigo and dizziness.
- Other symptoms vary depending on the location of the cyst.
- Source: Cleveland Clinic
How common is it? 1.4% (Al-Holou et al.)
DCC and Arachnoid Cysts:
More info about Arachnoid Cysts:
https://my.clevelandclinic.org/health/diseases/6023-arachnoid-cysts
Polymicrogyria
Definition: “Polymicrogyria is a condition characterized by abnormal development of the brain before birth. The surface of the brain normally has many ridges or folds, called gyri. In people with polymicrogyria, the brain develops too many folds, and the folds are unusually small.” (Medline Plus)
Characteristics:
- Seizures (main symptom)
- Cerebral Palsy
- Motor delays
- Cognitive and emotional delays
- Speech delays
- Swallowing problems
- Abnormal head size (too big or too small)
- Common cognitive or intellectual disorders connected to PMG include:
- Speech and motor function delays
- Autism
- Behavioral delays
- Dyslexia
- Epilepsy Foundation
How common is it? 2.3 in 10,000 children and 1.88% incidence rate (Kolbjer et al.)
DCC and Polymicrogyria:
More info about Polymicrogyria:
Heterotopia
Definition: “Heterotopia or neuronal heterotopia are macroscopic clusters of misplaced neurons (gray matter), most often situated along the ventricular walls or within the subcortical white matter.” (HPO)
Characteristics:
- Varied symptomology
- Epilepsy
- Source: Watrin et al.
How common is it? Unknown
DCC and Heterotopia:
More info about Heterotopia:
Chiari Malformation
Definition: “Chiari malformation is a condition in which brain tissue extends into the spinal canal. It occurs when part of the skull is misshapen or smaller than is typical. The skull presses on the brain and forces it downward.” (Mayo Clinic)
Characteristics:
- Vision changes like double vision, blurred vision, abnormal eye movements or light sensitivity.
- Hearing problems like a ringing sound (tinnitus) or hearing loss.
- Difficulty swallowing (drooling, vomiting or gagging), eating, drinking or speaking.
- Curved spine (scoliosis).
- Loss of bladder or bowel control.
- Fainting.
- Difficulty breathing while sleeping (sleep apnea).
- Source: Cleveland Clinic
How common is it? less than 1 in 1,000 (American Association of Neurological Surgeons)
DCC and Chiari Malformations:
More info about Chiari Malformations:
https://hpo.jax.org/browse/term/HP:0002308
https://my.clevelandclinic.org/health/diseases/6008-chiari-malformation
Malformation of other parts of the brain
Associated Complications
Seizures
Definition: “A seizure is a sudden burst of electrical activity in the brain. It can cause changes in behavior, movements, feelings and levels of consciousness.” (Mayo Clinic)
Characteristics:
- Wide range of symptoms
- Possible symptoms:
- Short-lived confusion.
- A staring spell.
- Jerking movements of the arms and legs that can’t be stopped.
- Loss of consciousness or awareness.
- Changes in thinking or emotions. These may include fear, anxiety or a feeling of already having lived the moment, called deja vu.
- Source: Mayo Clinic
How common is it? 66% of people with a DCC experience at least one seizure (Unterberger et al., 2016)
DCC and Seizures:
More info about Seizures:
https://www.mayoclinic.org/diseases-conditions/seizure/symptoms-causes/syc-20365711
https://my.clevelandclinic.org/health/diseases/22789-seizure
https://www.epilepsy.com/what-is-epilepsy/understanding-seizures
Septo-Optic Dysplasia
Definition: Under-development of the optic nerves, which are nerves that carry visual information from the eyes to the brain (Children’s Hospital of Philadelphia)
Characteristics:
- Wide range of characteristics
- Underdevelopment (hypoplasia) of the nerves that carry visual information from the eye to the brain (optic nerves)
- Abnormal development of the structures that separate the right and left halves (the midline) of the brain
- Hypoplasia of the hormone-producing gland (pituitary gland) at the base of the brain
How common is it? 1 in 10,000 live births (Patel et al., 2006)
DCC and Septo-Optic Dysplasia:
More info about Septo-Optic Dysplasia:
https://pmc.ncbi.nlm.nih.gov/articles/PMC2987262/
https://medlineplus.gov/genetics/condition/septo-optic-dysplasia/
Autism Spectrum Disorder (ASD)
Definition: “Autism spectrum disorder is a neurological and developmental disorder that affects how people interact with others, communicate, learn, and behave.” (NIH)
Characteristics:
- Wide range of characteristics
- Difficulties with social communication and interaction
- Restricted or repetitive behaviors or interests
- Developmental delays
- Source: CDC
How common is it?
⅓ of adults with ACC (33%) meet criteria for an ASD Diagnosis (Paul et al., 2014)
1 in 31 kids (3%) meet criteria for an ASD diagnosis (Cleveland Clinic)
DCC and ASD:
More info about ASD:
Genetic Disorders
DCC can be a symptom of a larger genetic abnormality.
Aicardi syndrome
Definition: Aicardi syndrome is a disorder that occurs almost exclusively in females. It is characterized by three main features that occur together in most affected individuals: agenesis or dysgenesis of the corpus callosum, seizures, and chorioretinal lacunae, which are defects in the light-sensitive tissue at the back of the eye (retina). (Medline)
Characteristics:
- Agenesis of the corpus callosum
- Seizures (epilepsy)
- Brain asymmetry
- Abnormal (in size and number) brain folds or grooves
- Brain cysts
- Large ventricles (fluid-filled brain cavities)
- Nerve cells collect in abnormal locations (heterotopia)
- Source: Cleveland Clinic
How common is it? At least 853 individuals in the US and over 4,000 worldwide (Kroner et al 2008)
DCC and Aicardi Syndrome:
More info about Aicardi Syndrome:
https://my.clevelandclinic.org/health/diseases/6028-aicardi-syndrome
Andermann syndrome
Definition: Andermann syndrome is a disorder that damages the nerves used for muscle movement and sensation (motor and sensory neuropathy). Agenesis or dysgenesis of the corpus callosum occurs in most people with this disorder. (Medline)
Characteristics:
- Agenesis or dysgenesis of the corpus callosum
- Abnormal or absent reflexes (areflexia)
- Weak muscle tone (hypotonia)
- Muscle wasting (amyotrophy)
- Progressive weakness and loss of limb sensation
- Tremors
- Delayed motor development
- Abnormal function in some cranial nerves
- Source: Medline
How common is it? 1 in 2,000 children in certain populations in Quebec (rare outside of this region) (Medline)
More info about Andermann Syndrome:
https://medlineplus.gov/genetics/condition/andermann-syndrome/
Meckel-Gruber syndrome
Optiz G syndrome
Sotos syndrome
Wolf-Hirschhorn syndrome
FOXG1 syndrome
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To learn more about co-occurring conditions and genetic factors related to disorders of the corpus callosum, consider visiting trusted medical resources, consulting with a genetic counselor or specialist, or connecting with support groups familiar with these topics.