Genetic Brain Disorders

Absence of the septum pellucidum is a rare brain condition. It happens when the thin membrane (septum pellucidum) between the two halves of the brain is missing. This condition can happen on its own or alongside other birth disorders of the brain. Most cases happen without a known cause.

Absence of the septum pellucidum by itself is not life-threatening, but there is no cure. Symptoms include:

• 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)  

Treatments are available for some symptoms. People with absence of the septum should regularly see specialists in neurology, endocrinology, and ophthalmology to check for any issues related to the condition.

Agenesis of the corpus callosum (ACC) is a brain disorder in which the main structure (known as the corpus callosum) that connects the left and right sides of the brain is partially or completely missing. It is caused by a disruption of brain cell migration during development.  ACC can occur as an isolated condition or in combination with other brain conditions, including Chiari malformations, Dandy-Walker syndrome, schizencephaly, and holoprosencephaly. The effects of ACC range from mild to severe, depending on whether other brain conditions are present. Other disorders of the corpus callosum include dysgenesis, in which the corpus callosum develops in a malformed or incomplete way, and hypoplasia, in which the corpus callosum is thinner than usual. Women and girls may have a sex-specific condition called Aicardi syndrome.

Aicardi syndrome is a rare, genetic neurological disorder in which all or part of the corpus callosum is missing. This disorder primarily affects newborn girls. Symptoms may include infantile spasms (a type of epilepsy), eye lesions, low muscle tone, microcephaly (unusually small head), increased muscle tone or stiffness (spasticity), intellectual problems and developmental delays, heterotopias (groups of brain cells that migrated to the wrong areas of the brain during development), numerous small (or too few) brain folds, and brain cysts. People with Aicardi syndrome also may have  skeletal issues, skin problems, facial asymmetry (in which one side of the face doesn’t exactly mirror the other side), small hands, and an increased occurrence of tumors.

Anencephaly is rare neurological disorder that involves a defect in the closure of the neural tube during fetal development. Infants with this disorder are born without a forebrain (the front part of the brain). The remaining brain tissue is often not covered by bone or skin.

Colpocephaly is a congenital brain disorder in which the occipital horns—located in the rear portion of the brain—are larger than normal. This happens because white matter in the posterior cerebrum has failed to develop or thicken. Other features may include movement problems, muscle spasms, and seizures.

The skull is made up of bony plates that allow the brain to grow while it develops. The skull plates are joined together by seams (called sutures), which allow for growth of the skull. Craniosynostosis is a developmental condition that occurs when the sutures in a developing baby’s skull plates join together  too early. This can be caused by a genetic issue, metabolic disease, or an overactive thyroid. Surgery can help relieve pressure on the brain and nerves and reshape the skull. Some children can use a helmet. The prognosis for development depends on the underlying condition, if there is one.

Dandy-Walker syndrome is a brain disorder caused by an unusual formation between the cerebellum and the fluid-filled spaces around it. The cerebellum is in the back of the brain and controls movement. Dandy-Walker syndrome is sometimes associated with an absence of the corpus callosum. Symptoms may include slow development of motor skills (the ability to control movements) and progressive growth of the skull in babies. In older children, symptoms can include pressure in the skull, irritability, throwing up, problems with balance or muscle control, and unusual eye movements. Dandy-Walker syndrome can be associated with unusual development of the head, heart, face, arms, or legs, although some children may never have symptoms.

Encephalocele is a rare neural tube disorder characterized by a sac-like protrusion of the brain and the membranes that cover the brain through an opening in the skull. The disorder is caused by failure of the neural tube to close completely as the fetus develops. The result is a groove down the middle of the skull, in the area between the forehead and nose, or at the back of the skull. The disorder is usually diagnosed immediately after birth and is often accompanied by abnormalities of the brain and face or other brain malformations.

Holoprosencephaly occurs when a developing baby’s brain does not sufficiently divide into left and right halves (known as hemispheres). The result is a single brain structure and significant skull and facial differences. In most cases, the malformations are so severe that babies die before birth. In less severe cases, babies are born with normal or near-normal brain development, but may have facial differences that affect the eyes, nose, and upper lip.

Hydromyelia occurs when an abnormal widening of the spinal cord’s central canal causes a cyst filled with cerebrospinal fluid (syrinx) to form. As spinal fluid builds up, it may put abnormal pressure on the spinal cord, and damage nerve cells and their connections. Hydromyelia occurs in the fourth ventricle in the brain and almost always happens in infants and children. It is associated with birth defects such as Chiari malformation type 2 and Dandy-Walker syndrome. Hydromyelia is like syringomyelia, but this neurological disorder mainly happens in adults. Symptoms may happen over time and may include weakness in the hands and arms, stiff legs, sensory loss in the neck and arms, and severe neck and arm pain. Surgery may permanently or temporarily help with symptoms such as loss of balance, speech, and memory, and help spinal fluid to flow normally. But it can also cause several serious complications. Rarely, hydromyelia may go away on its own.

Iniencephaly is a rare birth disorder caused by improper closure of the neural tube as the fetus develops. The disorder results in extreme backward bending of the head combined with severe distortion of the spine. Most infants have additional birth defects, such as anencephaly, cephalocele (in which part of the cranial contents protrudes from the skull), and cyclopia (in which the two cavities of the eyes fuse into one). Additional birth disorders related to iniencephaly may include the lack of a lower jawbone or a cleft lip and palate. Other parts of the body may be affected, and infants can have cardiovascular disorders, diaphragmatic hernias, and gastrointestinal malformations.

Klippel-Feil syndrome is a rare disorder where two or more vertebrae in the neck are fused together from birth. People with the condition may have a short neck with limited movement, pain, and hearing loss. People with certain genetic mutations are at higher risk of developing the disorder. Mutations in the GDF6 or GDF3 genes can cause the disorder. Treatment generally includes surgery to correct the neck bones. With proper treatment and care, people with Klippel-Feil syndrome can live normal lives. 

Lissencephaly, also known as agyria, is a condition in which the cerebral cortex develops without folds (convolutions) and the head is extremely small. It is a rare, gene-linked brain disorder. Children with lissencephaly usually have head sizes in the expected range at birth, but the head and brain do not grow at normal rates. Lissencephaly is caused by neuronal migration problems. In pachygyria, also called incomplete lissencephaly, there are few folds, and they are usually broad and flat. Lissencephaly may be associated with isolated lissencephaly sequence, Miller-Dieker syndrome, and Walker-Warburg syndrome.

Megalencephaly (also known as macrencephaly) is a condition in which an infant or child has a large, heavy, and potentially malfunctioning brain. The condition affects boys more often than girls. Unilateral megalencephaly or hemimegalencephaly is a rare condition in which one side of the brain is enlarged. Children with this disorder may have a large, asymmetrical head and experience epilepsy, partial paralysis, and impaired cognitive development.

Microcephaly is a medical condition in which the head is small because the brain has not fully developed or has stopped growing. Microcephaly can be present at birth or it may develop in the first few years of life. Microcephaly is associated with Down syndrome, chromosomal syndromes, congenital infections, and neurometabolic syndromes.

Polymicrogyria, also known as micropolygyria or microgyria, is a developmental disorder of the brain in which the ridges or folds, called gyri, on the surface of the brain do not develop normally. In people with polymicrogyria, the brain develops too many folds, and the folds are unusually small. Polymicrogyria can affect part of the brain or the whole brain. Symptoms of polymicrogyria depend on how much of the brain and which areas of the brain are affected.

Porencephaly is an extremely rare disorder of the central nervous system that causes a cyst or cavity filled with cerebrospinal fluid to develop in the brain. It is usually the result of damage from stroke or infection after birth, but it can also be caused by delayed development before birth (which is inherited and less common). Hydranencephaly is an extreme form of porencephaly in which the brain’s hemispheres are absent and replaced by sacs filled with cerebrospinal fluid. Symptoms may include epilepsy, vision problems, lack of growth, deafness, paralysis, and intellectual problems.

Schizencephaly is an extremely rare birth disorder in which there are abnormal slits, or clefts, in the left and right hemispheres of the brain. Babies with clefts in both hemispheres commonly have developmental delays, delays in speech and language skills, and problems with brain-spinal cord communication. Children with clefts in only one hemisphere (unilateral clefts) are often paralyzed on one side of the body but may have average to near-average intelligence. Individuals with schizencephaly also may have an abnormally small head, cognitive problems, partial or complete paralysis, and poor muscle tone. Most will have epilepsy. Some individuals may have an excessive accumulation of fluid in the brain called hydrocephalus.