Apart from neural tube defects and perinatal brain injuries, there are three other types of abnormalities that can result from faulty genes: forebrain malformations, posterior fossa abnormalities and spinal cord abnormalities. I will be discussing each of them briefly here.
The malformations that can happen in the forebrain can be either as a result of abnormal brain volume or by abnormalities in the structure.
There are two diseases when it comes to volume. Megalencephaly is defined as an abnormally large brain, and microencephaly is defined as an abnormally small brain, which is often associated with a small forehead otherwise known as microcephaly. The latter condition, as shown alongside, is the more common of the two. Several genetic and environmental factors can cause this defect to occur: they include HIV-1, foetal alcohol syndrome, and chromosome abnormalities.
Abnormal Gyration in the Brain
There are three conditions associated with abnormal gyration of the brain: pachygyria, polymicorgyria and holoprosencephaly.
Pachgyria is characterized by an abnormally smooth-surfaced brain, as the picture alongside demonstrates. The cerebral cortex of a person with pachgyria is also unusually thick in comparison to that of a normal brain. This condition is often caused by a fault within a single gene. Children with this condition tend to have delayed development and they may also experience seizures. Pachygyria and agyria are related syndromes: agyria is a more severe form of pachygyria due to the brain being completely smoothed out because there are no gyri. Both of these diseases also have the unfortunate consequence of causing early death: most of the people with pachgyria tend to die before they hit twenty years of age.
Polymicrogyria is essentially the opposite of pachgyria: instead of a lack of gyri, the number of gyri within the brain is increased. Additionally, these gyri are not shaped regularly: as the picture alongside shows, they appear stone-like or cobble-like from the surface layer. This abnormal appearance may be both global (throughout the entire brain) or isolated to a particular region. The symptoms of polymicrogyria are similar to that of pachygyria, with the addition of muscle weakness, paralysis and difficulties with speaking and swallowing.
Holoprosencephaly is another forebrain abnormality, and there are both mild and severe forms of the condition. Basically, people with holoprosencephaly have abnormalities with the midline of the brain that separates the different hemispheres and lobes. In the mild form, the olfactory bulbs (which help with our sense of smell) are absent and this form is known as arrhinencephaly. The severe form, on the other hand, can cause cyclopia (facial midline defects) which is demonstrated by the picture alongside.
Posterior Fossa Abnormalities
The posterior fossa, by definition, is the area of the brain which houses both the brain stem and the cerebellum. Posterior fossa abnormalities are often exhibited with hydrocephalus, and typical findings in these conditions include either a misplaced or lost cerebellum. There are three distinct types of posterior fossa abnormalities, and they are named after the scientists which discovered them: the scientists involved are Hans Chiari, Walter Dandy, and Arthur Earl Walker. These abnormalities are known as Chiari and Dandy-Walker abnormalities, respectively. I’ll be discussing each of them below. I’ll also be mentioning the foramen magnum a lot, and here is a picture of it to help you out. Essentially, the foramen magnum is a small hole in the bottom of the skull in which the spinal cord is able to pass between the brain and the spinal vertebrae.
Chiari I Malformation
Chiari I malformations present with obstruction of the cerebrospinal fluid and the medulla becoming compressed as a result of the cerebellum herniating and extending through the foramen magnum. The symptoms associated with the condition include the following: headaches, tiredness, difficulties with swallowing, loss of coordination, muscle weakness in the facial region and paralysis. Due to the fact type I CMs (Chiari malformations) are often asymptomatic up to a certain (trigger) point, this particular type of CM is the only type which can be acquired within early life (typically within teenage and young adult years) rather than develop in the uterus as a result of genetic defects. Type 1 CMs are treatable by surgery on the herniated region.
Chiari II Malformations (aka Arnold-Chiari Malformations)
Type II Chiari malformations are also known by two other names: both Arnold-Chiari malformations and ‘classic’ Chiari malformations. Unlike type 1, type 2 CMs consist of both the cerebellum and the brain stem region protruding through the foramen magnum, and it often exhibits hydrocephalus and a lumbar myelomeningocele, which is similar to spina bifida, only higher than the typical location in which spina bifida is seen. The presence of this myelomeningocele often results in people with this condition having paralysis in area below the malformation. Addtionally, the cerbellular vermis (the tissue which helps connect the two separate cerebellar lobes) is either only partially there or missing entirely.
Dandy-Walker malformations can be easily distinguished from Chiari malformations, as the posterior fossa is enlarged rather than shrunken in size. As shown by the shadow in the MRI picture alongside, the cerebellar vermis (the part of the brain which separates the two cerebellar hemispheres) that protudes through the foramen magnum in Chiari malformations can be either missing, or it may be deformed. Other features that may be seen include cyst formation and enlargement of the fourth ventricle. Symptoms associated with this condition include delays in motor development and skull enlargement in infancy, and symptoms associated with increased intracranial pressure (ICP) such as irritability, vomiting, and convulsions in older children.
Spinal Cord Abnormalities
There are three different types of spinal cord abnormalities that can result from genetic alteration, and they are known as hydromyelia, syringomyelia and syrinx. The latter two conditions are often mentioned together, so I’ll do so here, and discuss hydromyelia separately. These conditions are unrelated to other, more well-known conditions such as spina bifida due to the fact that they have nothing to do with the structure of the spine or the skin overlying it.
Hydromyelia is defined as excess CSF within the central canal of the spinal cord, as shown in the cross-section of a vertebrae below.
Syringomyelia and Syrinx
Syringomyelia is defined as the formation of either a cavity or a cyst within the spinal cord, otherwise known as a syrinx. Symptoms associated with this condition are progressive over time due to the expansion of the syrinx eventually destroying the spinal cord, and they can be exacerbated by coughing and sneezing. Such symptoms include paralysis, weakness, pain, stiffness and inability to detect extremes in temperature (very bad!) The syrinx may also develop in other manners, such as during trauma or via tumour development in the spine.