Lissencephaly

About the condition & what this means for Owen

As Lissencephaly effects the brain, Owen is effected globally and a lot of secondary diagnosis come along with it.

Owen not only has Lissencephaly but also suffers from:

  • Spastic Quadraplegic Cerebral Palsy (CP)
  • Cortical Vision Impairment (CVI)
  • Global Developmental Delay (GDD)
  • Epilepsy

What is Lissencephaly?

Lissencephaly, which literally means “smooth brain,” is a rare, gene-linked brain malformation characterized by the absence of normal convolutions (folds) in the cerebral cortex and an abnormally small head (microcephaly). In the usual condition of lissencephaly, children usually have a normal sized head at birth. In children with reduced head size at birth, the condition microlissencephaly is typically diagnosed. Lissencephaly is caused by defective neuronal migration during embryonic development, the process in which nerve cells move from their place of origin to their permanent location within the cerebral cortex gray matter. Symptoms of the disorder may include unusual facial appearance, difficulty swallowing, failure to thrive, muscle spasms, seizures, and severe psychomotor retardation. Hands, fingers, or toes may be deformed. Lissencephaly may be associated with other diseases including isolated lissencephaly sequence, Miller-Dieker syndrome, and Walker-Warburg syndrome. Sometimes it can be difficult to distinguish between these conditions clinically so consultation with national experts is recommended to help ensure correct diagnosis and possible molecular testing.

Is there any treatment?

There is no cure for lissencephaly, but children can show progress in their development over time. Supportive care may be needed to help with comfort, feeding, and nursing needs. Seizures may be particularly problematic but anticonvulsant medications can help. Progressive hydrocephalus (an excessive accumulation of cerebrospinal fluid in the brain) is very rare, seen only in the subtype of Walker-Warburg syndrome, but may require shunting. If feeding becomes difficult, a gastrostomy tube may be considered.

What is the prognosis?

The prognosis for children with lissencephaly depends on the degree of brain malformation. Many will die before the age of 10 years. The cause of death is usually aspiration of food or fluids, respiratory disease, or severe seizures. Some will survive, but show no significant development — usually not beyond a 3- to 5-month-old level. Others may have near-normal development and intelligence. Because of this range, it is important to seek the opinion of specialists in lissencephaly and support from family groups with connection to these specialists.

What is X-linked lissencephaly? (the type Owen has)

X-linked lissencephaly is a condition of abnormal brain development that mainly affects males, though females may be mildly affected. Normally the exterior of the brain (cerebral cortex) is multi-layered with folds and grooves. People with lissencephaly have an abnormally smooth brain with fewer folds and grooves. This abnormality can cause severe intellectual disability and developmental delay, seizures, abnormal muscle stiffness (spasticity), weak muscle tone (hypotonia), and feeding difficulties. People without any folds in the brain (agyria) typically have more severe symptoms. There are at least two forms of X-linked lissencephaly. The first is characterized by lissencephaly only, and usually involves no other parts of the body. – This is what Owen has.

The second is lissencephaly with abnormal (ambiguous) genitalia. This form of X-linked lissencephaly is typically more severe, with seizures often beginning within the first day of life, and sometimes even before birth. In addition, affected males can have an unusually small penis (micropenis), undescended testes (cryptorchidism), or external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Males with this form of X-linked lissencephaly also can show a lack of development (agenesis) of the tissue connecting the left and right halves of the brain (corpus callosum), low body temperature (hypothermia), and chronic diarrhea.

How common is X-linked lissencephaly?

The overall incidence of lissencephaly is estimated to be 1 in 100,000 individuals. The incidence of males with X-linked lissencephaly is unknown.

What genes are related to X-linked lissencephaly?

X-linked lissencephaly is caused by a mutation in either the DCX gene or the ARX gene. Mutations in the DCX gene cause isolated lissencephaly, which typically does not involve any other parts of the body. Mutations in the ARX gene can cause X-linked lissencephaly with ambiguous genitalia and other associated health issues. Both genes provide instructions for producing proteins that play a role in the development of the brain. The DCX protein, doublecortin, plays a role in the migration of nerve cells (neurons) to their proper location in the developing brain. The ARX protein is involved in the regulation of other genes that contribute to brain development. The ARX protein is also found in the pancreas and testes.

X-linked lissencephaly is seen primarily in males. Most females with a DCX mutation have a milder brain disorder called subcortical band heterotopia, or doublecortex. Females with an ARX mutation usually have some degree of intellectual disability, epilepsy, and agenesis of the corpus callosum.

How do people inherit X-linked lissencephaly?

This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.

 

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Spastic Quad Cerebral Palsy


Spastic quadriplegia, the most severe form of CP, means Owen has trouble moving his entire body. His arms, legs, torso, neck and head control is affected to such a degree that even eating, drinking and speech is difficult. You may notice that children with spastic quadriplegia are usually skinny. This is because the muscles use up lots of energy because they are always tense.

Cerebral palsy (CP) is a disorder that affects muscle tone, movement, and motor skills (the ability to move in a coordinated and purposeful way). CP is usually caused by brain damage that occurs before or during a child’s birth, or during the first 3 to 5 years of a child’s life.

The brain damage that leads to cerebral palsy can also lead to other health issues, including vision, hearing, and speech problems, and learning disabilities.

There is no cure for CP, but treatment, therapy, special equipment, and, in some cases, surgery can help a child who is living with the condition.

The three types of CP are:

1. Spastic Cerebral Palsy – causes stiffness and movement difficulties
2. Athetoid Cerebral Palsy – leads to involuntary and uncontrolled movements
3. Ataxic Cerebral Palsy – causes a disturbed sense of balance and depth perception

Cerebral palsy affects muscle control and coordination, so even simple movements – like standing still – are difficult. Other vital functions that also involve motor skills and muscles – such as breathing, bladder and bowel control, eating, and learning – may also be affected when a child has CP.

 

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Cortical Vision Impairment

Cortical visual impairment (CVI) is a term used to describe visual impairment that occurs due to brain injury. CVI differs from other types of visual impairment which are due to physical problems with the eyes. We find that Owen’s vision is very hard to determine and can fluctuate day to day. CVI is caused by damage to the visual centers of the brain, which interferes with communication between the brain and the eyes. The eyes are able to see, but the brain is not interpreting what is being seen.

Cortical visual impairment (CVI) is often referred to by other terms including: cerebral visual impairment, neurological visual impairment, brain damage related visual impairment and so forth. All of these terms refer to visual dysfunction resulting from injury to visual centers of the brain. We will always refer to it as cortical visual impairment or CVI.

Typical Characteristics of CVI

  • Preference for a specific colour.

You may have noticed that your child seems to prefer looking at a certain colour. Bright red and yellow are often favourite colours, but some children prefer other bright colours such as blue, green, or pink.

  • Need or preference for movement.

Many children with CVI require movement in order to see an object. For example, it may be easier for them to look at a pinwheel or a swaying balloon.

  • Delayed response when looking at objects (visual latency).

It may take time for a child with CVI to look at an object. Often they will look at an object and then look away. For this reason it is important to give your child enough time when presenting an object.

  • Difficulty with visual complexity.

Children with CVI need simplicity. First, it is important that the object presented is simple. For example, a single coloured stuffed animal, like Elmo, is preferable to one with multiple colours. Likewise, it is important that the background and the environment are simple. For example, putting a solid black cloth behind a single coloured toy helps to reduce visual clutter. Creating a simple environment is a matter of eliminating noise and anything else that might distract from the visual task.

  • Light-gazing and nonpurposeful gazing.

Often, children with CVI will stare at light. They may be seen gazing out the window or up at a ceiling light. They may also appear as if looking at things that are not there, or looking at things without intent.

  • Visual field preferences.

Most children with CVI will prefer to look at objects in a particular direction. For example, they may see an object better when it is presented in their periphery, or may turn their head to see an object.

  • Distance vision impaired.

Some children with CVI have trouble seeing far away. This is related to the preference for visual simplicity. Objects far away may be lost in visual clutter.

  • Visual blink reflex is absent or impaired.

When an object comes too close to the eyes, or touches the bridge of the nose, many CVI children have an absent or delayed protective blink response.

  • Preference for familiar objects.

Because it is difficult for CVI children to process the information that the eyes see, they often prefer familiar objects that the brain easily recognizes and has processed before.

  • Impaired visually guided reach.

The ability to look at an object while reaching for it is impaired. Often CVI children will look away from the object and then reach for it.

 

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Global Development Delay


Global Developmental Delay is defined as significant delay in two or more developmental domains. Owen is delayed in all areas. He has Global developmental Delay owing to conditions such as Cerebral Palsy, neuromuscular disorders and/or early environmental deprivation. Children with Global developmental delay will not necessarily have intellectual impairment. Early diagnosis does improve outcomes. The different areas of development that may be delayed include:

  • Motor skills (Gross and Fine)– e.g. rolling, sitting up, walking or picking up smack objects
  • Speech and language development – e.g. identifying sound, imitating speech sounds, babbling
  • Cognitive development – the ability to learn new things or to reason
  • Social and emotional development – making friends, sharing, turn-taking
  • Daily activities – e.g. eating, dressing

 

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Epilpsy tendencies


Currently Owen has had no seizures, he is classed to have epilepsy tendencies as he does have abnormal brain activity and EEG’s have shown that he has sparks in brain activity. He is currently on antiepelepic medication, clonazapam and this may be why we have seen no seizures.

What is epilepsy?

Epilepsy is a disorder of brain function that takes the form of recurring convulsive or non-convulsive seizures. Epilepsy is not just one condition; rather it is a diverse family of disorders comprising many seizure types

10% of the population are at risk of experiencing a seizure during their lifetime, while 3-4% will go on to be diagnosed with epilepsy.

There are seizures that are not epileptic such as those that result from diabetes, kinked blood vessels and a range of other health conditions.

What causes epilepsy?

There are many causes of epilepsy, which vary with the age at which seizures begin and the nature of the seizures. However 50% of cases, the cause is unknown.

We know that structural abnormalities in the developing brain, infections such as meningitis or encephalitis, or lack of oxygen to the brain during birth or after a stroke, can cause epilepsy. A brain injury, which results in scar tissue, predisposes individuals to developing epilepsy, although there can be a long period, often years, between the damage occurring and the seizures commencing. Why this occurs, we still do not know. Epilepsy can result from a tumour (an uncommon cause in children) and, in the over 65s from degenerative conditions such as Alzheimer’s disease.

Current research has identified that in many cases of epilepsy in very young children, genetics play an important role. But genetics can be a factor in developing epilepsy at any age. It appears that certain people are simply more prone to having seizures than others. This is, at times, described as having a ‘low-seizure threshold’. A history of seizures in the family makes it more likely for them to develop epilepsy.

 

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